Shards of electricity burned through Mr Ps flesh. Layers upon layers of subcutaneous fat unraveled, filling the operating room with a pungent, metallic odor, like singed hair at the neighborhood barbecue. Within a few minutes, the pearly white bone of the sternum stuck out before a vein split open, filling the operative field with blood.

Zap! Maroon juice turned into a crackly black mass.

Transplant surgery is all about timing, says Dr Brandon Guenthart, a cardiothoracic surgeon at Stanford University School of Medicine. Anesthesiologists put the patient to sleep after the retrieval team confirms the donor heart looks good. Two surgeons start operating an hour before the donor heart arrives in the hospital. They dont begin cutting the patients heart out until the donor heart has landed safely at the local airport.

And if the plane crashes? Knock on wood, says Guenthart. Theres unfortunately no wood in the operating room.

I was at Stanford hospital watching this heart transplant because of my interest in David Bennett, a 57-year-old man who had died back in March. On 7 January 2022, at the University of Maryland Medical Center, Bennett had received a landmark heart transplant from an unusual donor: a genetically modified pig.

In 2021, a record 41,354 human-to-human organ transplants were performed, but over 100,000 Americans are still stuck on the transplant list. Every day, 17 people die waiting because there simply arent enough organs to go around.

Xenotransplantation or transferring cells, tissues and organs between species promises to solve this shortage and to reshape how we think about human longevity.

Lost in this boundless potential, however, is the significance of the human-animal divide. People walking around with pig organs melded into their bodies human-animal cyborgs of sorts can seem dystopian. And with the zoonotic Sars-CoV-2 virus having killed more than 6 million people, violating the interface between humans and animals may just promise more catastrophe.

This tortuous relationship is nothing new, but its often sanitized and hidden from sight think grinning cows on milk cartons and secret bunkers for animal research. Left open is a whole host of questions, starting with the most complex of all: what does it mean to be human?

Humans are animals. But animals are not humans. And yet, our history is rife with a cultural imagination of hybridity. The ancient Egyptian god of the sky, Horus, was depicted with a falcon head and the goddess of war, Sekhmet, that of a lioness. Similarly, the Hindu god Ganesha was beheaded and then resurrected with an elephant head grafted on to his body. In ancient Greece, fantastical creatures roamed the myths, from the bull-headed Minotaur to the snake-haired Medusa.

Within this wealth of options, the International Xenotransplantation Association chose a more obscure mascot: the Lamassu, an Assyrian deity with the body of a bull, the wings of a bird, and the head of a man a grounding wisdom.

Xenotransplantation, as a research field, started only with cells and tissues. In 17th-century France and England, blood was transfused from animals to humans to cure a whole host of medical conditions. Spiritual meaning was imbued into the act: Since Christ is the lamb of God, one recipient wrote in a letter to the Royal Society, sheeps blood possess[es] a symbolic relationship with [his] blood. One patients violent fever was purportedly cured, as was another patients paralysis, but at least two others died soon after these xenotransfusions.

Other early xenotransplants would follow, including ones with the bone, cornea and skin. Perhaps most infamously, the French surgeon Serge Voronoff transplanted slices of chimpanzee and baboon testicles into men, and ape ovaries into women, to rejuvenate his patients zest for life. Thousands of these operations were performed around the world, but any reported benefit, such as reduced fatigue or increased sex drive, was probably only the placebo effect and quickly faded.

While cell and tissue xenotransplants have been performed for centuries, whole organ transplants were more difficult to figure out. Sewing all the blood vessels together is a tricky business. You have to put two floppy tubes together mouth-to-mouth, tying them tight enough that the patient doesnt bleed out, but delicately enough that the patient doesnt have major clotting either.

This was a Nobel prize-level problem that the French surgeon Alexis Carrel solved with a small embroidery needle and fine silk suture, and was recognized for in 1912. Hes sometimes known as the father of transplant surgery.

A half-century later in 1964, the University of Mississippi surgeon James Hardy attempted the worlds first cardiac transplant, transferring Bino the chimpanzees heart into the chest of the rapidly deteriorating 68-year-old Boyd Rush. Rush survived for only 90 minutes, with the chimp heart offering insufficient support and rejection quickly shutting down his body.

It was Baby Fae who truly set the stakes for xenotransplantation. She was a 12-day-old infant with hypoplastic left heart syndrome, a congenital abnormality where the left side of the heart is a sliver of its full form. The condition was a death sentence.

So, in 1984, surgeons at Loma Linda University, California, transplanted a walnut-sized baboon heart into Baby Faes chest. The conditions were almost perfect. The heart was well-sized, Baby Faes immune system was immature (and sympathetic), and the immunosuppressive drug cyclosporine could suppress attacks on the baboon heart.

After the operation, Baby Fae seemed to be doing well. Resting in her crib with a gauze-covered scar traversing her chest, she was just gulping down her formula and wailing with a lusty cry, according to the hospital spokeswoman. The hospital also released photos of Baby Fae talking with her mother, the phone receiver bigger than her entire torso.

She died 21 days after her operation, her immune system refusing to accept the new infant-baboon hybrid. Outrage from physicians and the public soon followed, with animal-rights activists protesting and bioethicists publishing articles like Baby Fae: The Anything Goes School of Human Experimentation.

Xenotransplantation died with Baby Fae, if only for a little while.

During surgery when the drapes are on, its not really a person, Guenthart said. Its a task.

Technically speaking, a heart transplant is pretty easy. It takes only five incisions to cut out the failing heart, and only five connections to put in the new one. Electrocautery in one hand, scissors in the other, you usually first cut out the superior vena cava the vessel bringing back blood to the heart from the head, neck, arms and chest because its the most accessible structure.

Next is the inferior vena cava, which brings back blood from down south but is a bit hard to reach. So, you cut off a portion of the hearts right chamber where this vessel drains into.

Then comes the aorta and pulmonary arteries in fairly simple, straightforward incisions. More difficult are the pulmonary veins, because these are four delicate vessels that are almost impossible to reconnect. The way around that is to lift the heart up and cut out a rim of left heart tissue from underneath. You create a swimming pool, or a little crater, Guenthart said. He paused. Thats just me giving a description. They dont actually call it a swimming pool.

Regardless of whether youre transplanting a human heart or pig heart into someone, the steps are essentially the same.

If you asked 99 doctors out of 100, they wouldnt be able to tell you if they were looking at a human chest or pig chest, Guenthart said.

Pigs are filthy animals, as conventional wisdom goes. Judaism and Islam prohibit consumption of pork and other unclean meat. The insult cops are pigs bears undeniable teeth. And in the Odyssey, the sorceress Circe transforms Odysseuss gluttonous men into swine.

Pigs are also highly intelligent animals, capable of showing emotions. Some 11,000 years ago, wild pigs may have domesticated themselves, recognizing a benefit to allyship with humans. They like playing fetch, are whizzes at navigating mazes, and can outsmart dogs and chimpanzees, according to their IQ tests.

Following the Baby Fae experiment, primates fell out of favor for xenotransplantation, and pigs became the new model organism for researchers to develop.

If you ask xenotransplantation experts today, theyll give a laundry list of reasons why pigs are better than baboons: they are more easily genetically manipulated, they can be raised in a sterile environment to reduce infections, and they can be grown to give organs of any size needed.

Its a nice packaged narrative, but Dr Brad Bolman, historian of science at the University of Chicago, argues that sheep, goats or some other animal could have been deemed suitable instead. At the outset, Bolman said, it wasnt obvious that pigs were the right replacement for non-human primates. But when pigs were chosen, the scientific ideals were constructed retroactively to make them seem like the clear choice all along.

Bolman says that pigs were chosen because it was socially and economically convenient. They produce large litters quickly, with piglets reaching adult human size in six months. Theres also an almost unlimited supply of them 700 million worldwide and as agricultural animals, they arent covered by the Animal Welfare Act.

We treat pigs in ways that we would never treat people, but we also recognize theyre so similar to us that theyre our models, said Dr Lisa Moses, a bioethicist and veterinarian at Harvard Medical School. You cant make sense of that because it doesnt make sense. Its one giant paradox. Pigs are close enough to give their lives for ours but not close enough that their plight gives us pause.

Maybe it should. If you subscribe to Kantian ethics, its wrong to use others as a means to an end, so it feels downright exploitative to genetically modify a pig and kill it for its heart. People for the Ethical Treatment of Animals (Peta) has thus decried pig-to-human transplants as unethical, dangerous, and a tremendous waste of resources, asserting that animals arent toolsheds to be raided but complex, intelligent beings. Kathy Guillermo, a senior vice-president at Peta, went even further to proclaim, pigs are people.

These ethical concerns arent new. In 1999, the Campaign for Responsible Transplantation protested in New York Citys famous Halloween Parade, with members dressed up as genetically engineered monsters. As millions of Americans watched the parade on TV, these snout-wearing attendants hoisted a 13ft-tall mad scientist puppet, sporting a dollar sign tie and clenching a pig-human hybrid.

But the xenotransplantation experts I spoke to often dismissed these ethical concerns by citing the structural fact of the global pork industry. The thinking goes that, if pigs are going to be eaten anyway, they might as well be used for science, a more valuable and noble pursuit.

If you think about eating in a slightly more capacious sense, Bolman said, eating is really about consumption and rendering animals destroyable. More than anything else, the edibility of pigs justifies their usage for xenotransplantation and research at large.

What science does is consume animals, even if they arent literally eaten, said Bolman. Science remains carnivorous.

Mr Ps new heart had arrived in the operating room a half-hour ago, and Guenthart was zigging and zagging a fine thread across the arc of two vessels to cinch them together.

Six oclock, seven oclock, eight oclock Guenthart stitched together one half of the artery before he grabbed another needle to run around counterclockwise. Once the two sutures had circled around and met at noon, he threw a right-handed knot, and then another. Then left-right-left-right-left-right, each opposing throw locking the last one into a square knot, Guentharts hands dancing with the fine thread.

During the entire operation, everyone in the operating room was chatting away, but now it was so silent you could hear the faint music that had been playing all along. This was the crucial moment where, with the donor heart actively dying, Guenthart was sewing as fast as he could to restore blood flow to the heart. Every second counted.

Clamp off, Guenthart finally announced. With the pressure released off the aorta, blood rushed into the coronary arteries and fed the heart.

Having graduated from medical school a decade ago, Guenhart joked that xenotransplant is the promise thats 10 years out and always will be. But he also sees Bennetts 60-day survival as an amazing milestone and xenotransplantation as the most promising solution for the organ shortage killing his patients.

After about 30 seconds, Mr Ps new heart started beating on its own, like a zombie rising from the dead. Guenthart hadnt connected any of the nerves and definitely nothing to his brain. The hearts internal pacemaker is the circus master of its own show.

Xenotransplantation requires selective humanization of a pig. If you transplant a pig heart into a human, just like that, it will get rejected. Specifically, itll turn an ugly black and be flooded with blood clots, according to Dr Richard Pierson, director of the Center for Transplantation Sciences at Massachusetts general hospital. (I spoke with Pierson as he was speeding down to the hospital for a human-to-human lung transplant, ambulance sirens hollering in the background.)

Because our immune police force is so good at its job, the Virginia-based biotech company Revivicor used the gene-editing technology Crispr to create a special line of pigs with 10 modifications. Four genes are knocked out, and six genes are added in.

So, what is the recipe for making a pig heart fit for humans?

1. Knock out three sugar genes that are only found in pigs. Most of us think if you have a pig with those three genes knocked out, thats probably better than just one. We dont know that for sure, Pierson said.

2. Knock out a growth hormone gene to prevent the pig heart from overgrowing its new home. Pierson said, Is growth at the graft going to be a problem? We dont know.

3. Add two complement inhibitor genes that prevent antibodies from destroying the pig heart and two anti-clotting genes that stop the patients blood from curdling inside the foreign organ.

4. Add two anti-inflammatory genes to prevent the pig heart from swelling up. One of these genes signals to the immune system that the pig heart is a friend (self), not food (nonself). That may or may not be necessary, said Pierson. It probably is helpful, but we havent proven that.

After all this cutting and pasting, the next challenge is to keep the pig clean. The last thing you want is to transplant a pig heart with viruses, bacteria and parasites that cause infections in humans.

Therefore, these pigs are raised in pathogen-free facilities. There are no windows. They dont go outside. The air is filtered and sterilized, said Dr Leo Buhler, editor-in-chief of the journal Xenotransplantation and professor of surgery at the University of Fribourg.

After the genetically engineered embryos are implanted, the surrogate sows have to undergo caesarian sections (a vaginal birth is more likely to cause an infection.) The piglets are then immediately taken to isolation boxes under infrared lights, allowed to suckle their mother only every two hours under scientist supervision.

After 24 hours, the sows are all removed from the facility, and the piglets are artificially fed with a motherless rearing system and formula. Any interaction with humans must happen with the highest level of personal protective equipment.

With this pig-in-a-bubble approach, you should get a line of pigs that has never had any contact with the outside world and whose exogenous, or external, viruses have all been eliminated. These pig hearts are safe to implant into humans then, right?

Not exactly. Bennetts heart still tested positive for pig endogenous retroviruses (PERV) viruses built into the porcine genome that can jump into human cells, at least in a Petri dish. Its an alarming example of zoonosis that could lead to a pandemic like Covid-19.

Whether or not those viruses can infect humans remains to be seen, but Pierson doesnt think it will be a major barrier to xenotransplantation. HIV drugs seem to be relatively effective against them, and Boston-based biotech company eGenesis has already made a 60-gene PERV-free pig.

So what does worry Pierson about xenotransplantation?

The unknown unknown, he said. You can run a battery of tests in search of viruses, but you might only find what youre looking for. And with a cocktail of immunosuppressants required to sedate our trigger-happy immune system, any infection that crosses the pig-human barrier could wreak devastating consequences.

Doesnt this all feel a bit premature, then? I ask Pierson.

Worry is not a reason not to do things. You need to take cautious steps forward. If the problem presents itself, you figure out a way to solve it. You dont just go home.

For months, Bennetts transplant had been shrouded in secrecy, but the details of the operation were finally unveiled in a mid-June report of the New England Journal of Medicine. One of the studys blockbuster findings was that Bennett was infected with a pig virus. The paper itself is neutral on the cause of death, but the cardiothoracic surgeon and study first-author Dr Bartley Griffith is slightly betting that a pig virus killed Bennett.

The pig virus hes referring to is not a PERV, however; its an external virus called porcine cytomegalovirus (pCMV).

pCMV is a member of the herpes family, and its human form is known for causing mononucleosis, the kissing disease. Dont let that fool you though. Cytomegalovirus causes inflammation and damage to the organ, Pierson told me. A lot of damage.

pCMV is also one of the viruses that Revivicor had supposedly eliminated from pigs through all their precautions; it has been a well-recognized threat to xenotransplantation for decades.

When it first showed up, we thought maybe it was just an error or something, Griffith said, discussing how a routine blood draw on the 20th day after surgery returned a tiny blip.

Possible pCMV infection was so unimaginable to Griffiths team that they werent even looking for this pig virus and discovered the infection only on accident. Griffith told me, The first thing we did is we went to the company and said, How can we possibly be seeing this?

One xenotransplantation expert who wished to remain anonymous for legal reasons thinks that Revivicor may have gotten a bit slack about their protocol. He says the evidence is clear that, with early weaning and all other precautions, pigs dont get pCMV.

Revivicor, of course, tested the donor pig several times with a nasal swab and PCR, getting negative results every single time. It looks like PCR is not sufficient to exclude silent pCMV that can reactivate in an immunosuppressed environment, Buhler wrote to me. He suggests that Revivicor made an honest mistake by not using a more specific test. (Revivicor did not respond to repeated queries sent by the Guardian.)

Regardless of why pCMV was missed, the results were gruesome on autopsy. After hitchhiking into Bennett, the virus seems to have exploded some capillaries and killed the heart.

But Griffith is continuing to march along, hoping to do another xenotransplant in the next few months, even if he isnt entirely sure yet why Bennett died. Whatever it was, hes confident that it can be overcome. A pCMV infection? Exclude it. Too much immunosuppression? Reduce it. The anti-pig antibodies they gave Bennett? Dont do that again.

Thats how you make progress, Griffith said. You admit where you made errors, and you try to limit them. But you move on.

In a world where we are humanizing pigs with Crispr and piggifying humans with xenotransplantation, what does it even mean for there to be a human-animal divide?

In some ways, the word divide is problematic. After all, theres no bright red line separating humans from other animals. Pigs and humans share 98% of genes, and that 2% is critically important. But its also just 2%.

Moses, the Harvard bioethicist, believes that the notion of a human-animal divide is an artificial construct. Theres been a concerted effort from the biomedical research community to enhance the perception of that divide, going back as far as Descartes and Francis Bacon, she said.

Built on a shaky foundation, the separation between animals and humans has been reified over millennia. Look no further than the impossibly low sticker prices of a pack of bacon that hides environmental externalities and inhumane conditions under a crisp cellophane wrap. Its easier to not think too hard about it.

But we cant not think hard about xenotransplantation. If its promise is to be realized, well have to, at the very least, create a whole new economy of factory farming, where pigs will be manufactured and slaughtered en masse to give us life.

Sure, 1.5 billion pigs are already killed each year. And sure, if the people you loved most had heart failure, lungs slowly drowning in fluid, their dilated heart twisting agonizingly, youd probably take the pig heart instead of gambling with the transplant list. I would, at least. But that shouldnt obviate the need to tread carefully here.

Dr Chris Walzer, executive director of the Wildlife Conservation Society, thinks xenotransplantation could benefit from the OneHealth framework the idea that human, animal and environmental health are all connected.

Take the Nipah virus as an example. Nipah is a zoonotic disease that has caused deadly outbreaks in Malaysia, Singapore, Bangladesh and India. For years, these outbreaks were a mystery to epidemiologists, who couldnt understand how the transmission chain worked between fruit bats the natural hosts of the virus and humans. And ultimately, it took a broadened perspective to solve this puzzle tracing how date palm trees bloomed in the winter, how fruit bats infused tree sap with saliva and urine, and how humans consumed that infected sap and got Nipah.

Its too simple to say pigs are people. And its too simple to say pigs are an unlimited supply of organs. Seventeen people die every day waiting on the transplant list, but xenotransplantation is about a whole lot more than just saving these lives.

Were all part of a shared ecology. And theres a danger to ignoring our interconnectedness.

Earlier that day, Guenthart had told Mr P that he was getting a new heart. Mr P started crying. Hes in his early 20s, and three months ago, his heart started failing without any apparent reason. His doctors still arent sure why.

It was hard for me to not also start crying, Guenthart said.

A heart transplant is a highly technical operation, but for the patient, its a chance at life. When David Bennett had his xenotransplant, he didnt just get a pig heart; he got two more months of life. He watched the Los Angeles Rams win the Super Bowl. He sang America the Beautiful with his therapist. He spent time with his five grandchildren, every day begging his surgeons to let him go home to his dog Lucky.

Now that the transplant was over, Guenthart was calling Mr Ps mom.

The surgery went really well. The new heart looks beautiful, and hes doing amazing. Hes asleep right now, and were sending him over to sleep in the ICU.

Yes, hes going to be two floors above where he was before.

Normal visiting hours are from 8am to 7pm, but you can call them at any time and get updates directly from his nurse.

Of course, youre so welcome, and I hope to see you tomorrow.

Original post:
Pig to human heart transplants are the future. Are we ready for it? - The Guardian

"In your 50s, that's when you're really implementing some of those prevention techniques," says Spar, noting that the bulk of his patients seeking performance-based medicine fall into this age group. To stay proactive, he also recommends snagging a wearable health tracking device, if you can. That way, you can assess everything from your sleep to your stress to your blood sugar levels and make precise, personalized tweaks.

And if you are going to focus on one specific avenue, stress is a good place to start (long-term stress, after all, can affect your health in sinister ways). "At least figure out a way to know what stress feels like in your body," he says. "Get to know when you're stressed and what you could do to attenuate that. Try out different apps for meditation or breathwork, prayer, journaling. What can you be doing around your diet and supplements? Just try very consciously different things to tweak what your concerns might [be]."

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How To Boost Longevity In Your 20s, 30s, 40s & Beyond - mindbodygreen.com

Story at a glance

Busy Americans may not have time during the week to fit in the American Heart Associations recommended 150 minutes of moderate intensity exercise. But new research from nearly 351,000 adults shows the benefits of exercising only on the weekends are comparable to those seen among more regular exercisers.

Writing in JAMA Internal Medicine, researchers explained how they assessed data from the National Health Interview Survey which took place between 1997 and 2013. Authors classified those who completed all their recommended weekly exercise in one or two sessions as weekend warriors and those who spread out sessions as regularly active.

Participants were followed for a median of 10.4 years and within that time frame, 4,130 people died of cardiovascular disease and 6,034 from cancer.

Similar all-cause mortality hazard ratios were reported for weekend warriors and regular exercisers when compared with inactive participants. Cause-specific mortality hazard ratios were also similar between the two active groups.

America is changing faster than ever! Add Changing America to your Facebook or Twitter feed to stay on top of the news.

According to the authors, findings reinforce the importance of reaching the recommended levels of physical activity for health.

They continued, for people with fewer opportunities for daily or regular physical activity during their work week, these findings are important.

Exercise can help prevent onset of several non-communicable diseases in addition to combating obesity and weight gain. Currently, 42 percent of the United States population is obese and 9.2 percent are classified as severely obese.

The papers findings underscore the importance of meeting total exercise time thresholds each week, as opposed to how often one exercises or at what time of day.

The self-reported nature of questionnaires marks a limitation to this study, as participant bias may have impacted results. However, a large sample size and the long duration of the study bolsters the conclusions reliability.

Published on Jul. 07, 2022

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Exercising only on the weekend is still effective, study finds - The Hill

I enjoy a good streaming service, be it Netflix, Disney+, or Amazon Prime. Admittedly, one of my favorite places to log in, and the stream is from my bed. However, one thing Im not guilty of is falling asleep while catching up on the latest episode of Squid Game. In fact, it appears that I was protecting my longevity when doing this, as a new study has revealed that falling asleep in front of the TV could lead to an early death.

The study, published in Sleep, set out to find a link between late at night activities in older adults in the U.S. and its association with cardiovascular disease (CVD) risk factors. For the study, researchers from the Northwestern School of Medicine examined the impact of ambient light on the health and sleeping habits of 552 people between the ages of 63 and 84.

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The findings revealed that participants who slept under ambient light were more likely to experience hypertension, diabetes, obesity, and insulin resistance in the morning. In fact, 17.8% of the participants who slept with the TV on suffered from diabetes, compared to only 9.8% who didnt sleep with the TV on. Also, 40.7% of participants who slept under ambient light were obese, compared to the 26.7 who were also obese but slept in darkness.

For the team, the results of the study can be linked back to the fact that sleeping under ambient light affects glucose regulation, and insulin resistance has been associated with Type II diabetes, cardiovascular disease, and hypertension.

According to a previous study published in PLOS Medicine, extreme obesity can shorten your lifespan by 14 years. Additionally, research has also found that people with type 2 diabetes, on average, have a shorter life expectancy of about 10 years.

In addition to the aforementioned findings, the study also revealed that participants who fell asleep in ambient light were more likely to stay awake later and then sleep later the next day.

We know late sleepers tend to also have a higher risk for cardiovascular and metabolic disorders, Lead researcher Phyllis Zee told CNN.The saying the early bird catches the worm is anything but a common expression. In fact, one 2018 study suggested that night owls have a 10% heightened risk of early mortality.

People should do their best to avoid or minimize the amount of light they are exposed to during sleep, Phyllis Zee, CNN

Its not just your TV habits that are a cause for concern at night, as any screen that emits blue light can affect your sleep health, which in turn can compromise your longevity. If youre worried about your devices affecting your sleep hygiene, then heres how you can safely use your tech at night.

Tech at night tips:

At 46 years old, Eva Longoria is truly the embodiment of health and wellness. As the years go by, the Desperate Housewives actress continues to prioritize her longevity. In fact, she recently shared two health habits that had changed in her 40s, and these two could be the key to why shes aging so well: eating well and sleeping well.

Kitahara, C. M., Flint, A. J., Berrington de Gonzalez, A., Bernstein, L., et al. (2014). Association between class III obesity (BMI of 40-59 kg/m2) and mortality: a pooled analysis of 20 prospective studies.PLoS medicine,11(7), e1001673. https://doi.org/10.1371/journal.pmed.1001673

Kim, M., Vu, T. H., Maas, M. B., Braun, R. I., Wolf, M. S., Roenneberg, T., Daviglus, M. L., Reid, K. J., & Zee, P. C. (2022). Light at night in older age is associated with obesity, diabetes, and hypertension.Sleep, zsac130. Advance online publication. https://doi.org/10.1093/sleep/zsac130

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Falling Asleep With The TV On Is Affecting Your Longevity - Longevity LIVE - Longevity LIVE

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The Dog Aging Project digs deeper than ever to help our best friends live better longer - The Union Leader

Infertility is a medical condition affecting a growing number of couples worldwide. The good news is that in many cases it can be successfully treated. In this #WellnessWednesday session Gisle Wertheim Aymes discussed infertility with specialistDr. Tebogo Deo.

Dr. Deo is a Reproductive Medicine Sub-specialist, and Fertility Gynaecologist. She trained at the University of Cape Town in South Africa and the University of Warwick in the United Kingdom. She also holds a B.Sc. from Rhodes University and MBCHB from MEDUNSA. Dr. Deo is currently completing her MA in Pastoral Studies.

Infertility is a medical condition that requires an accurate diagnosis and the right treatment. Its defined as failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse; or due to an impairment of a persons capacity to reproduce, either as an individual or with his/her partner.2 If the woman is older than 35, she and her partner should seek an evaluation if they have not been able to conceive after six months.3

Its estimated that globally, infertility affects 812 % of women who are 2044 years of age.1 Physiological causes in men account for 2030 % of cases of infertility and physiological causes in women for 2035 %, 2540 % of cases are due to issues in both partners. In 1020 % of cases, no cause was found.1

Infertility does not mean you cant fall pregnant or have a baby. Rather, you require medical assistance to do so, as infertility is a medical condition that can be treated.

In recent years, the number of couples seeking treatment for infertility has dramatically increased. This is due to many factors including the postponement of childbearing in women. It is a medical fact that a womans fertility begins to decline in her 20s and significantly deteriorates after age 35. The chance of conception for a woman older than 43 is very low. As increasing numbers of women postpone starting families until after 35, many require reproductive assistance.

Dr. Deo stressed, Its not necessarily just a mans issue or a womans issue, it is a couple issue. We need both of them together to understand this.

All of the steps during ovulation and fertilization need to happen correctly in order to get pregnant. Dr. Deo says that sometimes, issues that cause infertility in couples are present at birth, and sometimes they develop later in life. This can affect one or both partners.

Causes of male infertility may include abnormal sperm production or function. It can also be a result of problems with the delivery of sperm and overexposure to certain environmental factors. These include cigarette smoking, anabolic steroid use, marijuana, alcohol, and certain medications. Cancer can also impact fertility.3

Causes of female infertility may include ovulation disorders. Uterine or cervical abnormalities, fallopian tube damage or blockage and endometriosis. In addition, early menopause, pelvic adhesions (bands of scar tissue from pelvic infection, appendicitis, endometriosis, abdominal or pelvic surgery) can also cause infertility. Cancer is a factor.3

Tubes may be blocked as a result of diseases like TB, chlamydia and endometriosis .Fibroids can also be a cause, particularly those close to the tubes. They may cause infertility.

Dr.Deo explained that carrying excess weight can also influence the condition. And yes, if you are more than 40, you may find that your ovarian reserve, meaning the number of eggs that you have, are diminished. And as a result of that, you may not be able to fall pregnant. Men who are overweight may not be able to produce a lot of sperm. This is due to their male hormone being converted into the female hormone by the fat cells. Thats why they develop man boobs and this usually results in poor sperm production.

The long-term inability to conceive a child can evoke real feelings of loss and devastation in both partners. Infertility often creates one of the most distressing life crises a couple will experience together. Coping with the multitude of medical decisions and the uncertainties that infertility brings can create emotional upheaval for most couples.

We work with counsellors, like social workers, as well as psychologists. This is very stressful, and I think maybe thats one of the reasons why Im also doing my pastoral studies, because it can be spiritually draining. Wehave to have a holistic approach to the partners. We are very upfront with the information, especially the financial toll that it can take on the person and the emotional toll.

Fortunately, newer and more successful techniques for infertility treatment are developed continuously. Many people delay fertility treatment because they fear the costs associated with in vitro fertilisation (IVF). IVF is where sperm and egg are placed together in a lab until they form an embryo which is then implanted into your uterus.

However, there are a number of treatment options other than IVF that can improve the chance of conceiving. A specialist will recommend the treatment based on the cause of your fertility issues, your age, and your preferences. Some women may have to have surgery to fix a uterine condition, such as endometriosis, fibroids, or blocked fallopian tubes.

Dr. Tebogo Deo

Theres only one way to know for certain what the exact cause of a couples fertility challenges is, and that is an initial consultation with a fertility specialist. With advances in medical science infertility can be addressed. Couples must empower themselves with knowledge about the options that are available. Importantly, they should continue with their journey towards parenthood.

The video interview contains the full dialogue of this interview, and you can watch it below.

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Infertility is a medical condition and there are several ways to treat infertility - Longevity LIVE

The key to a long, happy retirement is not just having a flush portfolio or moving to a low-tax state with 300-plus days of sunshine. Its having the good health to enjoy your golden years.

And thats more than clich. Edward Jones surveyed 11,000 adults and found that 69% wanted to live to age 100. However, some didnt want such longevity if they were in terrible health (32%), if they became a burden on their families (29%), if they had serious cognitive loss (20%), and if they no longer had purpose in life (14%).

Many people assume that their chances of a long, healthy life is largely out of their hands, controlled by the genes they inherited. Its not that simple.

While scientists previously believed that genetics accounted for roughly 25% of lifespan, new research has put that number under 10%. Genetics still matters. Whether or not you dodge a particular affliction may be determined by your genes. And for extremely long-lived peoplethose who live beyond perhaps age 105genes are still thought to pay a huge role.

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Barrons brings retirement planning and advice to you in a weekly wrap-up of our articles about preparing for life after work.

For most of us, however, whether we get 75 or 85 or 95 healthy years is affected more by lifestyle choices than by genes. Getting regular exercise and enough sleep, eating nutritious, healthy foods, staying resilient and connected with other humansthese are the habits that produce continuing good health, long lifespans and enjoyable, productive retirements. They will also lower your healthcare costs and reduce your odds of developing dementiatwo of the biggest worries for retirees.

Genetics are the gun and lifestyle pulls the trigger, says Dr. David Fein, medical director of the Princeton Longevity Center in New Jersey.

Barrons recently talked to longevity experts, geriatric doctors, and read the latest research to come up with some concrete steps for improving your odds of a long, healthy life. Some of it is age-old advice. But research has also upended some of the conventional wisdom in recent years. For example, doctors used to think that moderate alcohol consumption was good for you; new research shows otherwise.

Here are six things you can do to improve your chances for having the good health to enjoy your retirement.

Exercise isnt a particularly efficient way of losing weight. But it is great at just about everything else when it comes to improving your health.

Want to lower your blood pressure or your blood sugar levels? Want to sleep better? Want to improve your brain function and memory? Want to lift your spirits? All these things are important for our health, and over recent years, theres been much research showing how exercise helps in all.

Exercise doesnt necessarily mean going to the gym. Brisk daily walks around the neighborhood will give you similar benefits. Nor does exercise all have to be done in one continuous session. Little five- or 10-minute bursts of activity throughout the day could be even better for you than a single session.

Its very hard to make up for 47 hours of being sedentary with one hour of intensive exercise, says Dr. Fein. Chairs kill more people than anything else.

Especially as you get older, be sure to include resistance training or other weight-bearing exercises to strengthen your bones and retain muscle mass. Biking or swimming are great for your cardiovascular system but they wont protect you from osteoporosis. If youre not lifting weights, try a few minutes of jumping ropes to build stronger bones.

Can there be too much of a good thing when it comes to exercise? Some research has found that extreme exercise actually hurts your health. An in-depth study in 2018 found otherwise. It studied 122,000 patients and measured their fitness not on how much they said they exercised, but how they performed on a treadmill test. It found the extremely fit had the lowest mortality levels.

But the debate over how much exercise is too much is beside the point. The big difference in health isnt between those in good shape and those in extremely good shape. Its between those who exercise and those who dont.

All sorts of good things happen as you sleep. Cells renew themselves. Your body produces hormones, which helps restore the body and reset many of its functions. Not getting enough sleep hurts your immune function. Scientists have found that people who dont sleep enough are more likely to eventually develop dementia.

How much sleep is enough sleep? The rough rule is between six to eight hours a night for adults. But different people may have different patterns and still get enough sleep. Some people may wake up in the middle of the night, be up for an hour or two, and go back to sleep for a few more hours. Others may take a nap in the middle of the day.

What is the best pattern for you? We dont know, says Daniel Belsky, an assistant professor of epidemiology at Columbia Universitys Mailman School of Public Health, who says there hasnt been much high-quality research on the subject. What pattern is optimal for a person may depend on the life they lead.

Dr. Belsky says there has been good research on shift workers who work at night while others are sleeping, and they pay a health priceparticularly if their sleep times keep changing.

Other Americans have trouble sleeping, no matter what time it is. If that applies to you, doctors advise you to improve your sleep hygiene. Go to bed at the same time each night. Make sure your bedroom is dark and at a comfortable temperature. And dont keep checking your smartphone throughout the night.

For years, many doctors advised their patients that moderate drinking, particularly red wine, was good for them. After all, research had shown that moderate drinkers lived longer than both heavy drinkers and nondrinkers.

But new research has changed the conventional wisdom on the subject.

It finds the reason moderate drinkers had better health wasnt the alcohol; it is believed to stem from favorable lifestyle, socioeconomic, and behavioral factors.

Drinking increases your risks for heart disease, high blood pressure, diabetes and certain cancers. The risks appear minimal for light drinkers but increase with higher drinking levels.

Bottom line: Nobody should start drinking because they think its good for their health, says geriatrician Alicia Ines Arbaje, an associate professor at the Johns Hopkins University School of Medicine. Alcohol is directly toxic to the body. There is no amount that is beneficial.

Obesity is tied to a multitude of illnesses, including higher rates of diabetes, heart disease and many cancers. Obese people have been hit harder by the Covid-19 pandemic.

But it doesnt necessarily follow that going on a strict diet to shave off some pounds is good for you. Losing weight isnt that hard. But keeping weight off is quite hard, and yo-yoing up and down doesnt do your body any good.

Whats more, all fat isnt created equal. The subcutaneous fat that sits on our hips may be unsightly, but it doesnt appear to have big effects on our health. The nasty stuff is the visceral fat that surrounds our organs. It changes the hormones produced by the body, and is linked to diabetes, heart disease, certain cancers and Alzheimers disease.

The only way of knowing for sure how much visceral fat you have is some sort of body scan, which is expensive and not recommended by most health experts for the general population.

People with bigger waists or apple-shaped bodies tend to have more visceral fat. But even there it gets tricky since different ethnic groups, notably people of Asian heritage, have a tendency to carry more visceral fat.

Morgan Levine is an assistant professor at the Yale School of Medicine who studies aging and wrote the book True Age. Instead of focusing on your weight, she says people should exercise regularly and eat a healthy diet. The good news is that exercise does reduce visceral fat.

Weight is such a bad proxy or measure for what is contributing to health, Dr. Levine says. Its so much more complex than how heavy you are.

Further complicating things, while weight loss may be desirable for the general population, it often isnt for seniors because it can cause loss of muscle and can contribute to osteoporosis. Geriatrician Deborah Kado, who has done extensive research on bone health and is co-director of the Stanford Longevity Center in California, doesnt usually advise her older patients to lose weight.

I tell them its insurance if you go into the hospital, she says. There is a lot of data that indicates that weight loss, whether intentional or unintentional, has been associated with adverse health outcomes rather than health benefits.

Nutrition is one of the trickier areas to research. Its hard to know exactly what research subjects actually eat. And it can take years for health effects to emerge. Nonetheless, scientists are seeing eating patterns that contribute to longevity.

A study found that even 60-year-olds could add an average eight or nine years to their lives by abandoning a Western diet. The biggest gains came from eating more legumes, whole grains and nuts, and eating less red meat and processed meat. Eating more fish was also a plus. The effects of eggs, poultry and oil were less clear. If it sounds a lot like the Mediterranean diet, it is. But its emphasis on vegetables, legumes and whole grains also bears similarities to how people eat in other parts of the world known for longevity.

Americans eat too much protein, says Yales Dr. Levine. She says protein contributes to overly high levels of the human growth hormone, which is linked to certain cancers and appears to increase aging.

But once again, the recommendation changes when it comes to seniors. Older people dont process protein as well, and need more of it in their diet to maintain muscle mass, research has found.

Live long enough, and bad things are likely to happen to you or the people around you. How you deal with them is key. People who have a positive mind-set on things they cant control tend to have much better outcomes, says Dr. Kado, the Stanford geriatrician. She says it is almost the most important factor in how her patients fare.

People are social creatures. And we tend to be more resilient when we have strong social connections. This can come through our family, our friends, our church, or even our retirement community. There has been research showing that maintaining social connections is good for brain health. So go for a walk with a friend and eat an apple afterward.

When it comes to longevity, these are all steps in the right direction. Saving for that longer life, and retirement, is another story.

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Here's How to Maximize Your Healthy Years in Retirement. Eat Right and Exercise. - Barron's

Getting in a full workout daily can feel like a daunting task. The Centers for Disease Control and Prevention recommend two days a week of muscle-strengthening activities and a minimum of 150 minutes a week of moderate-intensity aerobic activity. And with all of your normal day-to-day tasks, squeezing in those 30 minutes of movement is often skipped over. But a recent study found that as little as 10 minutes of physical activity a day could have some serious health perks and even help you live longer.

The study published in the journal JAMA Internal Medicine set out to see if physical activity could increase the longevity of U.S. adult lives. Researchers used data from the National Health and Nutrition Examination Survey, where participants ages six and older were asked to wear an accelerometer (an instrument that measures vibration and acceleration) for seven days from 2003 to 2006. Researchers then used data from 4,850 participants that were 40 to 85 years old and followed up in 2015 to determine their self-reported health status.

Based on their analysis, the study estimated that approximately 110,000 deaths per year could be prevented if U.S. adults aged 40 to 85 increased their moderate-to-vigorous physical activity intensity (MVPA) by a small amountas little as just 10 minutes per day. In fact, increasing MVPA by 10, 20, or 30 minutes per day was associated with a 6.9%, 13%, and 16.9% decrease in deaths per year, respectively. Similar benefits were seen across men, women, Hispanics, non-Hispanic African Americans, and non-Hispanic Caucasians. (Its important to note that this data was observed prior to the COVID-19 pandemic, which has skewed mortality rates).

Even a little bit of activity every day can literally save over 100,000 lives.

This brand new study shows that even a little bit of activity every day can literally save over 100,000 lives a year and for 30 minutes a day over 270,000 U.S. lives a year. Thats amazing, says David Sabgir, M.D., a cardiologist, Walk With a Doc founder, and spokesperson for Fresh AvocadosLove One Today.

Seema Bonney, M.D., functional medicine doctor at the Anti-Aging and Longevity Center of Philadelphia agrees, adding that a goal of just 10 minutes a day is a great starting point to help you feel accomplished and potentially increase to that 20 or 30 minutes in time.

If you can even take 10 minutes out of your day, even if youre doing something else, like watching TV or taking a meeting, even 10 minutes a day has a pretty substantial improvement in living longer, she says. Its incredible and an awesome return on investment.

Its not news that regular movement is important to your overall health. It can improve everything from your weight, blood pressure, and cholesterol, to balance, energy, mood, and memory, explains Danine Fruge, M.D, A.B.F.P., Medical Director at Pritikin Longevity Center.

Once you hit your 30s, youll begin to experience age-related muscle loss called sarcopenia, losing on average three to five percent of muscle mass per decade, explains Dr. Fruge. But regular movement can help mitigate that muscle loss, protect from falls, and even increase longevity, she adds.

Additionally, regular exercise can improve your cognition and even reduce the risk of dementia, adds Dr. Vanita Rahman, M.D., clinic director of the Barnard Medical Center at the Physicians Committee for Responsible Medicine. And exercise can even help support your mental health by boosting endorphins and lowering cortisol levels caused by stress, Dr. Bonney adds.

Many health issues crop up in higher numbers as we age, like heart disease, cancer, arthritis, and Alzheimers. Having a tool as simple as walking or [foam] rolling 10 minutes or more a day is an incredible weapon to help fight disease, says Dr. Sabgir. He notes that for even better results, couple movement with a healthy diet of plenty of fruits, vegetables, dietary fiber, and unsaturated heart-healthy fats.

Of course, we want to be our best every day, but Dr. Bonney loves that this study found scientific evidence that just a little bit of movement a day can really make a major impact.

Even something as short as 10 minutes, which all of us have, can make a difference. A lot of patients will say they dont have enough time, but 10 minutes is really doable, she says. Here are some expert-approved ways to get in your 10 minutes today.

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New Research: Just 10 Minutes of Exercise a Day Could Extend Life for Those 40 and Over - Prevention.com

With life expectancy dipping slightly over the past few years in the UK, many are seeking easy interventions to improve their health. One specific diet established for its plentiful benefits can lower your cholesterol, cut your risk of heart disease and boost longevity.

A new study published in the journal BCM Medicine has found that a greater adherence to a certain diet is linked with lower mortality in adults over 65.

Packed with vitamins and nutrients, the diet is well-established for its positive effects on overall health.

The diet in question is the popular Mediterranean diet.

As the name gives away, the diet combines the authentic lifestyles of people who live by the Mediterranean Sea.

READ MORE:Cancer warning: The type of fish that's 'known to cause cancer' when eaten - pharmacist

Depending on the exact country, the diet varies slightly over the regions but includes similar principles.

The Mediterranean diet is generally packed with vegetables, fruits, legumes, nuts, beans, cereals, grains and fish.

And its staple linked to good heart health is olive oil.

Overall, this healthy diet is low in meats and dairy intake.

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There are two types of cholesterol: good one and bad one.

The bad is the one linked to the health problems. However, olive oil found in the Mediterranean diet can help lower it, the Mayo Clinic reports.

Olive oil is a source of monounsaturated fat, which can lower your cholesterol levels. The popular diet is also packed with nuts and seeds, which also contain this type of fat.

Plus, following this type of diet can make you less likely to consume saturated fats, responsible for boosting your cholesterol.

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How to live longer: The cholesterol-lowering diet that could boost your longevity - Daily Express

Oxid Med Cell Longev. 2017; 2017: 1259510.

1Institute of Food Security and Sustainable Agriculture, Universiti Malaysia Kelantan, Campus Jeli, 17600 Jeli, Malaysia

2Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Campus Jeli, 17600 Jeli, Malaysia

2Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Campus Jeli, 17600 Jeli, Malaysia

2Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Campus Jeli, 17600 Jeli, Malaysia

3Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia

1Institute of Food Security and Sustainable Agriculture, Universiti Malaysia Kelantan, Campus Jeli, 17600 Jeli, Malaysia

2Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Campus Jeli, 17600 Jeli, Malaysia

3Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia

Academic Editor: Jasminka Giacometti

Received 2017 Feb 17; Accepted 2017 Apr 9.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

There are several health benefits that honeybee products such as honey, propolis, and royal jelly claim toward various types of diseases in addition to being food.

In this paper, the effects of honey, propolis, and royal jelly on different metabolic diseases, cancers, and other diseases have been reviewed. The modes of actions of these products have also been illustrated for purposes of better understanding.

An overview of honey, propolis, and royal jelly and their biological potentials was highlighted. The potential health benefits of honey, such as microbial inhibition, wound healing, and its effects on other diseases, are described. Propolis has been reported to have various health benefits related to gastrointestinal disorders, allergies, and gynecological, oral, and dermatological problems. Royal jelly is well known for its protective effects on reproductive health, neurodegenerative disorders, wound healing, and aging. Nevertheless, the exact mechanisms of action of honey, propolis, and royal jelly on the abovementioned diseases and activities have not been not fully elucidated, and further research is warranted to explain their exact contributions.

Apiculture is the science and art of prolonging, sustaining, and retaining health by using products obtained from honeybee hives, such as honey, bee bread, bee venom, bee pollen, propolis, and royal jelly. Recent years have seen the fast application of bee products in both traditional and modern medicine. Currently, many studies are targeted toward investigating directed health benefits and pharmacological properties of bee products due to their efficacies, leading to the increasing development of nutraceuticals and functional food from these products. The concept of functional food refers to food that has the ability to promote better physiological or psychological health compared to traditional remediated and nutritional food. These effects positively contribute toward excellent health maintenance, well-being, and reduced chronic illness [1]. The present review focuses on the potential health benefits of bee products, including honey, propolis, and royal jelly.

Honey is a sweet liquid processed by the honey bee. Honey is recognized worldwide due to its high nutritive components that are beneficial for human well-being. It has been traditionally used by Egyptians, Greeks, Romans, and Chinese to heal wounds and diseases of the gut, including gastric ulcers. It has also been used as a remedy for cough, sore throat, and earaches [2]. In India, Lotus honey has been traditionally used to treat eye infections and other diseases. In addition to being used externally, honey is also used internally [3] as a functional food to provide energy and nourishment to enhance vital organs in the body [4]. This has been in practice since ancient times. The active components of honey, such as glucose, fructose, flavonoid, polyphenols, and organic acids, play an important role in its quality [5]. Honey is being produced in many countries all over the world and is recognized as an important medicine as well as energy-providing food due to its functional properties and nutritional values. Additionally, honey is well known for its biological, physiological, and pharmacological activities.

Propolis is generally known as the bee glue, which is a generic name that refers to the resinous substance accumulated by the bees from different types of plants. The word propolis is derived from Greek to mean defense for pro and city or community for polis, or the beehive, in other words [6]. Propolis functions in sealing holes and cracks and for the reconstruction of the beehive. It is also used for smoothing the inner surface of the beehive, retaining the hive's internal temperature (35C), preventing weathering and invasion by predators. Furthermore, propolis hardens the cell wall and contributes to an aseptic internal environment. Propolis generally becomes soft and sticky upon heating [7]. It also possesses a pleasant smell. Propolis and its extracts have numerous applications in treating various diseases due to its antiseptic, anti-inflammatory, antioxidant, antibacterial, antimycotic, antifungal, antiulcer, anticancer, and immunomodulatory properties.

Royal jelly, a white and viscous jelly-like substance, is a form of hypopharyngeal and mandibular gland secretion from the worker bees. It is also known as a superfood that is solely consumed by the queen bee. Royal jelly is also fed to the honeybee larvae upon hatching and helps to nurture the brood [8]. It is the exclusive nutriment offered to the immature young larvae in their first 2-3 days of maturation besides being used as a food specifically for the queen bee throughout her entire life cycle. Royalactin is the main compound in royal jelly that allows the morphological change of a larva into the queen bee [9]. This superfood is the main reason for the longevity of the queen bee compared to the other bees. Royal jelly is widely used as a dietary nutritional complex to help combat various chronic health conditions. Furthermore, it is one of the profitable remedies for human beings in both traditional and modern medicine. Many pharmacological activities such as antibacterial, antitumor, antiallergy, anti-inflammatory, and immunomodulatory effects have also been attributed to it.

Honey is also known as a supersaturated sugar solution. Natural honey is composed of 82.4% carbohydrates, 38.5% fructose, 31% glucose, 12.9% other sugars, 17.1% water, 0.5% protein, organic acids, multiminerals, amino acids, vitamins, phenols, and a myriad of other minor compounds. In addition, honey consists of minor amounts of bioactive components, including phenolic acid, flavonoid, and -tocopherol [10]. Honey constituents with health benefits include phenolic acids, flavonoids, ascorbic acid, proteins, carotenoids, and certain enzymes, such as glucose oxidase and catalase [11].

Propolis is the third most important component of bee products. It is composed mainly of resin (50%), wax (30%), essential oils (10%), pollen (5%), and other organic compounds (5%) [12]. Phenolic compounds, esters, flavonoids, terpenes, beta-steroids, aromatic aldehydes, and alcohols are the important organic compounds present in propolis [13]. Twelve different flavonoids, namely, pinocembrin, acacetin, chrysin, rutin, luteolin, kaempferol, apigenin, myricetin, catechin, naringenin, galangin, and quercetin; two phenolic acids, caffeic acid and cinnamic acid; and one stilbene derivative called resveratrol have been detected in propolis extracts by capillary zone electrophoresis [14]. Propolis also contains important vitamins, such as vitamins B1, B2, B6, C, and E and useful minerals such as magnesium (Mg), calcium (Ca), potassium (K), sodium (Na), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe). A few enzymes, such as succinic dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and acid phosphatase, are also present in propolis [15].

Royal jelly consists of water (50%60%), proteins (18%), carbohydrates (15%), lipids (3%6%), mineral salts (1.5%), and vitamins [16]. Based on modern spectrometric analysis, approximately 185 organic compounds have been detected in royal jelly. Royalactin is the most important protein present in royal jelly. In addition, royal jelly is composed of a significant number of bioactive compounds, including 10-hydroxy-2-decenoic acid (HAD), which has some immunomodulatory properties [17]. Fatty acid, proteins, adenosine monophosphate (AMP) N1 oxide, adenosine, acetylcholine, polyphenols, and hormones such as testosterone, progesterone, prolactin, and estradiol are other useful bioactive components reported to be present in royal jelly [18].

Honey, propolis, and royal jelly are highly rich in bioactive compounds (). Essential and nonessential compounds, such as polyphenols and vitamins occurring naturally as part of food chains, are considered bioactive. These compounds are naturally present in food and confer useful health benefits. Phenolic compounds are bioactive compounds. Phenols are defined as organic compounds with an aromatic ring that is chemically bonded to one or additional hydrogenated substituents in the presence of corresponding functional derivatives [19].

Important bioactive compounds in honey, propolis, and royal jelly.

In honey, propolis, and royal jelly, phenolic compounds are commonly present as flavonoids [20]. Various phenolic compounds contribute to the functional properties of bee products, including their antioxidant, antimicrobial, antiviral, anti-inflammatory, antifungal, wound healing, and cardioprotective activities [21]. summarizes the important biological efficacies of bee products.

Various types of biological activities of honey products.

Honey has traditionally been used to treat wounds, insect bites, burns, skin disorders, sores, and boils. Scientific documentation of the wound-healing capabilities of honey validates its efficacy as a promoter of wound repair and an antimicrobial agent [37]. Honey promotes the activation of dormant plasminogen in the wound matrix, which results in the dynamic expression of the proteolytic enzyme. Plasmin causes blood clot retraction and fibrin destructions. It is an enzyme that breaks down fibrin clots with attached dead tissues in the wound bed [38].

Clinical evidence supporting the effectiveness, specificity, and sensitivity of honey in wound care indicates that the performance of conventional and modern wound care dressing is inferior to that using honey [39]. Certain cases have shown that honey stimulates wound-healing properties even in infected wounds that do not respond to antiseptics or antibiotics and wounds that have been infected with antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) (Natarajan et al. 2001). Honey also aids autolytic debridement and accelerates the growth of healthy granulated wound bed [40].

Malodor is a general attribute of severe wounds caused by anaerobic bacterial species belonging to Bacteroides spp. and Peptostreptococcus spp. [41]. Malodourous compounds, such as ammonia, amines, and sulfur, are produced by bacteria during the metabolism of amino acids from putrefied serum and tissue proteins. These compounds are replaced by lactic acids as honey dispenses a substantial amount of glucose, a substrate metabolized by bacteria in preference to amino acids [42]. The therapeutic effects observed after honey application include fast healing, wound cleansing, clearance of infection, tissue regeneration, minimized inflammation, and increased comfort during dressing due to lower extent of tissue adhesion [43].

Honey also controls skin damage near stomas, such as ileostomy and colostomy, by enhancing epithelialization of the afflicted skin surface [44]. Honey has a beneficial effect on pediatric dermatitis caused by excessive use of napkins and diapers, eczema, and psoriasis. The effect of honey mixed with beeswax and olive oil was investigated on patients with psoriasis or atopic dermatitis condition. A clinical trial showed that a mixture containing honey was extremely well tolerated and caused significant improvements. Honey consists of various nitric oxide metabolites, which reduce the incidence of skin infection in psoriasis [45].

Consumption of honey is a low-cost and effective therapy for the treatment of DFU. DFU is often complicated by microbial infections and slows the healing process. Apart from the infection, symptoms such as pain, swelling, and redness might not be present for diabetic peripheral neuropathy patients due to their reduced immune response, which further complicates the diagnosis [46]. A review indicated that using honey for the treatment of venous ulcers yielded positive outcomes with good acceptance rates from the patients [47]. Honey is used in wound management and is effective among patients with locally infected wounds, DFU, Charcot foot ulcerations, and complex comorbid conditions that have failed hospital management [48]. In addition, there is excellent tolerability and minimal trauma to the wound bed in the presence of honey.

Natural honey is composed of enzymes that facilitate the absorption of molecules, such as sugars and starch. The sugar molecules in honey are in a form that can be easily absorbed by the body. Honey also provides some nutrients, such as minerals, phytochemicals, and flavonoids, that aid digestive processes in the body [49]. Pure honey has bactericidal properties against pathogenic bacteria and enteropathogens, including Salmonella spp., Escherichia coli, Shigella spp., and many other Gram-negative species [50].

The gastrointestinal tract (GIT) contains many important beneficial microbes. For example, Bifidobacteria is one of the microorganisms present primarily for the sustenance of a healthy GI system. It has been suggested that consuming foods rich in probiotics can increase the population of Bifidobacteria in the GIT. The biological activities and development of this bacteria are further enhanced in the presence of prebiotics. Studies have shown that natural honey contains high amount of prebiotics [51]. Some in vitro and in vivo experimental trials on honey have reported it as a prominent dietary supplement that hastens the growth of Lactobacillus and Bifidobacteria and catalyzes their probiotic potency in the GIT [52, 53]. Under in vitro conditions, prebiotic ingredients in honey such as inulin, oligofructose, and oligosaccharides promoted the increase in the numbers of Lactobacillus acidophilus and L. plantarum by 10100 folds, which was beneficial for the intestinal microbiota [54].

Honey is useful for the treatment of many oral diseases, including periodontal disease, stomatitis, and halitosis. In addition, it has also been applied for the prevention of dental plaque, gingivitis, mouth ulcers, and periodontitis. The antibacterial and anti-inflammatory properties of honey can stimulate the growth of granulation tissue, leading to the repair of damaged cells [55]. Porphyromonas gingivalis is a Gram-negative bacteria that causes periodontitis. Honey exerts antimicrobial activity against this anaerobic bacteria and prevents periodontal disease [56]. Inflammation of mucous membranes in the mouth (stomatitis) may induce redness and swelling of oral tissues and cause distinct and painful ulcers. Honey penetrates into the tissues very quickly and is effective against stomatitis [57, 58]. Halitosis is an oral health condition that causes malodorous breath. Most of the odor in the oral cavity is caused by the activity of degrading microbes [59]. A recent study has reported that honey consumption ameliorates halitosis due to its strong antibacterial activity resulting from its methylglyoxal component [60].

Pharyngitis, commonly known as sore throat, is an acute infection induced by Streptococcus spp. in the oropharynx and nasopharynx [61]. In addition to streptococci, viruses, nonstreptococcal bacteria, fungi, and irritants such as chemical pollutants may also cause sore throat. Manuka honey is effective for treating sore throat with its anti-inflammatory, antiviral, and antifungal properties. Honey coats the inner lining of the throat and destroys the harmful microbes while simultaneously soothing the throat [62, 63].

A survey has demonstrated that honey is superior to other treatments for cough induced by upper respiratory infections, including dextromethorphan and diphenhydramine [64]. The antioxidant and antimicrobial properties of honey aided in minimizing persistent cough and ameliorated sleep for both children and adults following honey intake (2.5ml). A comparative study on children with different natural products reported that honey was found to be the widely used remedy for pneumonia 82.4% [65].

Gastroesophageal reflux disease (GERD) is a mucosal infection caused by contents of abnormal gastric reflux into the esophagus and even the lungs. Symptoms of GERD include heartburn, inflammation, and acid regurgitation. Consumption of honey helps this condition by coating the esophagus and stomach lining, thus preventing the upward flow of food and gastric juice. Honey can further stimulate the tissues on the sphincter to assist in their regrowth and finally reduce the chances of acid reflux [66].

Dyspepsia is a chronic disease in which the GI organs, mainly the stomach and first part of the small intestine, function abnormally. It is a disease that causes epigastric pain, heartburn, bloating, and nausea as symptoms. Dyspepsia is the preliminary symptom of peptic ulcer which could eventually cause cancer. Gastritis refers to the irritation and inflammation of the lining of the stomach wall. Peptic ulcer denotes erosions or open painful ulcers on the lining of the stomach or duodenum. Honey have been identified as a potent inhibitor for gastritis and the peptic ulcer causing agent, Helicobacter pylori (H. pylori) [67]. Clinical surveys have shown that honey decreased the secretion of gastric acid and increased the healing effect. Thus, honey is taken as a dietary supplement for its antibacterial properties and protective effect [68]. The high sugar content and low pH in honey are the results of glucose oxidative conversion to gluconic acid by glucose oxidase. This mechanism releases hydrogen peroxide, which functions as an antibacterial agent. Glucose oxidase also acts on fibroblasts and epithelial cell activators required for the healing of ulcers caused by H. pylori [51].

Gastroenteritis, known as stomach or gastric flu, causes inflammation of the digestive tract. This condition may be due to foodborne, waterborne, and person-to-person spread of infectious agents. The symptoms of gastroenteritis include dehydration, watery diarrhea, bloating, abdominal cramps, and nausea. There are many infectious agents, such as Salmonella, Shigella, and Clostridium, that can cause this condition [69]. A clinical study by Abdulrahman, 2010, has reported the treatment of infantile gastroenteritis using honey. The study found that replacing the glucose in standard electrolyte oral rehydration solution (ORS) with honey reduced the recovery time of patients with gastroenteritis because the high sugar content in honey boosts electrolyte and water reabsorption in the gut [70].

Chronic constipation is a common and multifarious illness characterized by intolerable defecation (irregular stools and difficult stool passage). Difficult stool passage includes symptoms such as straining, hard to expel stool, a sense of incomplete evacuation, hard or lumpy stools, and prolonged time to pass stool [71]. Diarrhea is defined as a high frequency of bowel movements with watery stool. Honey has minimized the pathogenesis and duration of viral diarrhea compared to conventional antiviral therapy [72]. In another case, people diagnosed with inflammatory bowel syndrome (IBS) experiencing severe diarrhea or constipation, bloating, and stomach discomfort was successfully treated with raw Manuka honey on an empty stomach [73].

Honey helps to soothe pain, balance liver systems, and neutralize toxins. Complications in the liver system can be attributed to oxidative damage. Honey exhibits antioxidant activities that have a potential protective effect on the damaged liver. A study on paracetamol-induced liver damage rats showed that the antioxidant and hepatoprotective activity of honey minimized liver damage [74]. Honey, which has a 1:1 ratio of fructose to glucose, may help to promote better blood sugar level, which is useful for those suffering from fatty liver disease since it provides adequate glycogen storage in liver cells. Insufficient glycogen storage in the liver releases stress hormones that impair glucose metabolism over time. Impaired glucose metabolism leads to insulin resistance and is the main factor of fatty liver disease. Another study reported significant reduction in blood glucose levels after treatment with Tualang honey [75, 76].

Natural wild honey exerts cardioprotective and therapeutic impacts against epinephrine-induced cardiac disorders and vasomotor dysfunctions. A harmonized relationship between radical scavenging activity and the total phenolic content of honey has been observed [77]. Honey intake showed a significant reduction in risk factors of metabolic and cardiovascular diseases. Honey exhibits cardioprotective effects such as vasodilation, balancing vascular homeostasis, and improvements in lipid profile [78]. Flavonoids in honey improves coronary vasodilation, decreases the ability of platelets to form clots, prevents oxidation of low-density lipoproteins (LDL), increases high-density lipoproteins (HDL), and improves endothelial functions [79].

A study conducted to compare the metabolic response of honey has indicated its ameliorative effects against metabolic syndromes (MetS) [80]. MetS is denoted by hyperglycemia, hypertension, abdominal obesity, dyslipidemia, and intensified adaptability towards diabetes, kidney, and heart diseases. Polyphenols in honey reduce atherosclerotic lesions through the downregulation of inflammatory and angiogenic mechanisms [81]. A clinical study conducted on patients with hyperlipidemia showed that honey decreased total cholesterol (TC) and noticeably prevented the rise in plasma glucose levels. Nitric oxide (NO) is a metabolite present in honey that also has cardioprotective functions [82].

Imbalance in estrogen signaling pathways and propagating levels of estrogens have important roles in breast cancer growth and propagation [83]. Treatments for breast cancer are associated with targeting the estrogen receptor (ER) signaling pathway. Phytoestrogens are a subclass of phytochemicals with a common structure to the mammalian estrogen that enables them to bind to estrogen receptors. Several experimental studies have investigated the efficiency of honey in modulating the ER signaling pathway [84]. Another study has shown that honey has biphasic activity in MCF-7 cells. This biphasic activity of honey is represented by an antiestrogenic effect at lower concentrations and an estrogenic effect at higher concentrations, which is caused when phytoestrogens bind to estrogen receptors [85]. Moreover, quercetin has been reported to induce apoptotic effects through ER - and ER -dependent mechanisms. On the other hand, cytotoxic activities of Tualang honey in human breast cancer cells were demonstrated by elevated secretion of lactate dehydrogenase (LDH) and further illustrated the cytotoxic properties of honey. The study also showed that honey only exerts cytotoxic effects on breast cancer line and not on nonmalignant breast cells. Therefore, this indicates that Tualang honey shows highly specific and selective cytotoxic effects towards breast cancer cell lines and has a good potential as a chemotherapeutic agent [86].

The most common type of liver cancer is hepatocellular carcinoma (HCC). The antitumor effects of honey on liver cancer cells have been investigated in various experimental studies. Treatment of HepG2 cells with honey minimized the amount of nitric oxide (NO) levels in the cells and decreased the HepG2 cell number greatly. This increased the overall antioxidant profile of the cells. The survival of HepG2 cells is promoted by reactive oxygen species (ROS), and adequate levels of ROS trigger cell proliferation and differentiation. Decreasing the amount of NO resulting from honey treatment supported this study. Thus, reduced ROS and enhanced antioxidant efficacy inhibit cancerous cell proliferation and lowered the number of HepG2 cells [84]. Another study done by Abdel Aziz et al. investigated the effects of honey on HepG2 cell lines. The report showed that honey exerted cytotoxic, antimetastatic, and antiangiogenic effects on HepG2 cells based on different concentrations [87].

Most colorectal cancers begin as a polyp, which generally starts on the inner lining of the colon or rectum and grows towards the center. Some polyps are not dangerous but some will eventually grow into adenomas and can eventually result in cancer. A study [88] that investigated the chemopreventive effects of Gelam and Nenas monofloral honeys against colon cancer cell lines found that the honey inhibited proliferation of colon cancer cells. Hydrogen peroxide-induced inflammation in the colon cancer cells was used to examine the effect of honey. The results showed that honey curbed inflammation in the cancerous cells [88]. Another study was done to investigate the apoptotic effects of crude honey on colon cancer cell lines. The study confirmed the antiproliferative effect of honey in these cells. In addition, at high phenolic concentrations (such as those of quercetin and flavonoids), significant antiproliferative action against colon cancer cells was observed [89].

The molecular mechanisms resulting in the antiproliferative and anticancer effects of honey include cell cycle arrest, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, reduction of inflammation, modulation of insulin signaling, and inhibition of angiogenesis in cancer cells (). In addition, honey shows potential effects on cancer cell by modulating proteins, genes, and cytokines that promote cancer.

Molecular mechanisms responsible for anticancer and antitumor activities of honey products. IRSinsulin receptor substrate, MAPKmitogen-activated protein kinase, NF-Bnuclear factor kappa B, IL-1interleukin-1 beta, IL-6interleukin-6, TNF-tumor necrosis factor alpha, iNOSinducible nitric oxide synthase, COXcyclooxygenase, ROSreactive oxygen species, Bcl-2B-cell lymphoma-2, and PARPpoly (ADP-ribose) polymerases.

Several components of honey such as chrysin, quercetin, and kaempferol have been shown to arrest cell cycle at various phases such as G0/G1, G1, and G2/M in human melanoma, renal, cervical, hepatoma, colon, and esophageal adenocarcinoma cell lines. The mitochondrial pathway entails a chain of interactions between stimuli such as nutrients, physical stress, oxidative stress, and damage during major cancer treatments including chemotherapy and radiotherapy. These stimuli cause several proteins located within the intermembrane space (IMS) of the mitochondria, such as cytochrome c, to be released, which eventually culminates in the death of the cell. Flavonoids in honey are effective in activating the mitochondrial pathway and discharging proteins with potential cytotoxicity. Induction of mitochondrial outer membrane permeabilization (MOMP) is the most prevalent anticancer mechanism, which causes the leakage of proteins from the IMS and inevitably results in cell death. Honey induces MOMP in cancer cell lines by decreasing the mitochondrial membrane potential. Honey has also been documented for amplifying the apoptotic effect of tamoxifen by intensified depolarization of the mitochondrial membrane. Flavonoid constituents of honey, such as quercetin, have been shown to trigger MOMP and lead to cancer cell death [84].

Apoptosis is a programmed cell death functioning to control cell growth and remove damaged cells from the system. This process also involves MOMP and results in the discharge of IMS proapoptotic proteins such as cytochrome c to activate caspase cascades which results in further disruption of mitochondria and finally results in cancer cell death. Influence of honey on enzymes, genes, and transcription factors corresponding to apoptosis has been investigated. Poly (ADP-ribose) polymerases (PARP) are crucial enzymes involved in apoptosis and DNA repair. Inhibition of PARP activity renders the cells unable to repair damaged DNA and pass through the G2 and M phases of the cell cycle. Thus, cell cycle is arrested. Because DNA repair is impaired due to nonfunctioning PARP, the cells are being classified as damaged, and consequently, apoptosis activity may be augmented.

Inhibition of PARP activity by flavonoids in honey is a potential strategy for targeting cancers with defective DNA-damage repair. Bcl-2 and Bax are antiapoptotic and proapoptotic proteins, respectively. Bcl-2 is generally overexpressed in cancer. Tumor suppressor p53 is a transcription factor commonly inactivated in various types of tumors. It modulates transcription of genes involved in apoptosis [84, 90]. Honey enhances the upregulation of Bax and downregulation of Bcl-2. In addition, it activates caspases 3 and 9 and induces p53, thereby inhibiting cancer.

Low levels of ROS intensify cell proliferation while high levels lead to oxidative damage that contributes to various types of cancer. Regulation of redox homeostasis is vital for normal cell growth and proliferation. In this regard, honey is an influential antioxidant and free radical scavenger. The inhibitory effect of honey on cancer growth and proliferation is due to its ability to modulate oxidative stress. Honey exhibits anticancer properties via antioxidant or pro-oxidant mechanisms that are selectively dependent on the state of oxidative stress in the cancer cells. If cancer growth is rapid under high levels of ROS, honey acts as an antioxidant to prevent cancer cell growth by minimizing oxidative stress and scavenging the ROS. On the other hand, under low levels of ROS, it may also act as a pro-oxidant and promotes cancer cell growth by further generation of ROS and maximizing oxidative stress. Thus, the effects of honey on cancer cell death are different under different conditions [84].

Inflammation is a contributing factor for the dysregulation of physiological processes, which leads to various malignancies and cancers. Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-B) are the two main pathways responsible for inflammatory response in cells. Activation of MAPK and NF-B activates proinflammatory genes and generates inflammatory proteins or cytokines. These include cyclooxygenase-2 (COX-2), C-reactive protein (CRP), lipoxygenase-2 (LOX-2), interleukins (IL-1, IL-6), and TNF-. These components play crucial roles in both angiogenesis and inflammatory responses corresponding to cancer. IL-1, IL-6, and TNF- are cytokines that trigger cancer cell proliferation by maintaining the inflammatory phenotype in the tumor microenvironment. On the other hand, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) yield essential endogenous factors responsible for the tumor progression. The actions of iNOS can be either inductive or inhibitory depending on the tumor types.

Biological responses which facilitate inflammation can promote tumorigenesis as severe inflammation is the major factor for the development of cancer cells. Treating and soothing of inflammation aid to suppress the configuration of malignant and benign tumors. Honey helps to reduce the promotion and tumorigenesis and progression of cancer by reducing the expression of MAPK and NF-B in cancerous cells. MAPK cascades are the main signaling pathways in the regulation of cell proliferation, survival, and differentiation. NF-B is a transcription factor which is vital in the regulation of immune responses, inflammation, and oncogenesis. NF-B translocation to the nucleus and reduced IB degradation help to regulate the expression of genes involved in apoptosis and proliferation that are responsible for the development of cancer. Flavonoids found in honey have been shown to induce apoptosis and prevent the release of IL-1, IL-6, TNF-, iNOS, and COX-2 [84].

Tumors, malignancies, and cancers are usually enhanced by obesity and insulin-resistant type 2 diabetes mellitus. PI3K/Akt is an important pathway in insulin signaling. The PI3K/Akt pathway is also recognized in modulating substrates that are related to cellular growth, survival, and progression. Elevated levels of MAPK, NF-B, and insulin receptor substrate 1 (IRS-1) along with reduced levels of Akt expression have been actively linked to the development of insulin resistance. Honey components such as quercetin revive insulin resistance by increasing the expression of Akt while reducing the expression of IRS, MAPK, and NF-B. Modulation of insulin signaling by honey leads to anticancer activities [84].

Honey has debridement effects by boosting epithelialization and stimulates the development of granulation tissue through its angiogenic effect on the vasculature. Honey selectively stimulates angiogenesis in noncancer tissues through the production of hydrogen peroxide while inhibiting angiogenesis in cancer tissues. Honey has antiangiogenic effects that prevents the wound-healing response, reduces the viability of cancer cells, and lowers the incidence of metastasis by inhibiting the activities of gelatinase and protease. Honey prevents the development of cancer by blocking the three main stages of cancer formation known as initiation, proliferation, and progression [84].

Infection with parasites usually occurs upon contact with an infected surface. The symptoms of parasitic infection of the GI tract include abdominal pain, diarrhea, bloating, and nausea. Propolis has been reported to have several biological efficacies including anticancer, antioxidant, and anti-inflammatory activities (). There are a few studies that reported the clinical use of propolis in the treatment of viral infections. In one study, the in vitro effect of propolis ethanolic extract on the growth and adherence of Giardia duodenalis trophozoites was evaluated [91]. Propolis was shown to inhibit growth and adherence of the trophozoites. It also promoted the detachment of these parasitic organisms. Its efficacy against giardiasis has also been reported in a clinical study whereby children and adults with giardiasis-given propolis showed a cure rate between 52% and 60%, whereas those given the conventional drug showed a 40% cure rate. Another experimental study showed that propolis has antihistaminergic, anti-inflammatory, antiacid, and anti-H. pylori activities that can be used to treat gastric ulceration [92].

The biological activities of propolis.

Widespread causes of indicative vaginitis are bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). The depletion of Lactobacillus spp. in the vagina is a distinguished feature of vaginal infections. The infection is accompanied by an overgrowth of vaginal pathogens such as yeast-like fungi and an elevated vaginal pH. Diabetes patients are more prone to having vaginal infections caused by Candida albicans. A study conducted on the application of 5% aqueous propolis solution resulted in an improvement in vaginal well-being [93]. In addition to providing antibiotic and antimycotic actions, propolis provides early symptomatic relief due to its anesthetic properties. Thus, propolis may be used for Recurrent Vulvovaginal Candidiasis (RVVC) and can be an alternative option for patients who are unable to take antibiotics due to a concurrent pharmacological treatment. The effectiveness of propolis against conventional antifungal nystatin has shown satisfactory results. Propolis extract solution (PES) also show low toxicity in human cells and can be an alternative treatment for chronic vaginitis. In addition, PES has antifungal properties and it can be used as antibiofilm material for RVVC to counteract biofilm growth of C. albicans and resistance in antifungal drug [94].

The oral cavity has an abundant bacterial microflora and excessive bacterial growth may lead to several conditions such as oral diseases. Studies have shown that propolis may restrict bacterial-plaque development and periodontitis-causing pathogens because of its antibacterial properties [95]. Propolis solutions exert a selectively lower cytotoxic action on human gum fibroblasts compared to chlorhexidine. In addition to that, mouthwash containing propolis have shown effectiveness in healing surgical wounds. This encourages the use of propolis in solutions used as mouthwash [96]. Propolis solution can also be used to disinfect toothbrushes [97]. A 3% ethanolic extract of propolis toothpaste gel showed greater potency against gingivitis caused by dental plague in a group of patients [98]. Propolis extracts have also helped cure halitosis, a condition where an individual experiences unpleasant breath predominantly due to poor oral hygiene. Propolis toothpaste or mouthwash is used for their ability to reduce growth of bacterial plaque and pathogenic microflora that causes gingivitis and periodontitis. Thus, propolis also plays a role as a therapeutic agent [95].

A study reported that propolis has potential towards human breast cancer treatment due to its antitumor activity by inducing apoptosis on human breast cancer cells. It also exhibits low or no toxicity towards normal cells due to its selectively toxic properties against tumor cells and is believed that propolis may become a prominent agent to treat breast cancer [99]. Another study investigating the effect of ethanolic extract of Algerian propolis on melanoma tumor growth has shown that galangin, a common flavonoid in propolis remarkably induced apoptosis and inhibited melanoma cells in vitro [100]. Turkish propolis has also been shown to exert a selective cytotoxic action on human lung cancer cells by inducing endoplasmic reticulum stress, apoptosis, and caspase activity and by reducing the mitochondrial membrane potential. This indicates that propolis is able to minimize the cancer cell proliferation [101].

Propolis is widely used in dermatological products such as creams and ointments. Its use in skin care products is based on its antiallergy, anti-inflammation, antimicrobial properties, and promotive action on collagen synthesis. A recent study comparing the effect of propolis and the conventional drug silver sulfadiazine showed that propolis notably decreased free radical activity in healing the wound beds which supported the repair process. A clinical study on acne patients using ethanolic extract propolis showed its high efficacy in the treatment of acne vulgaris [102]. Propolis also shows positive collagen metabolism in the wound during the healing process by increasing the collagen content of tissues [103]. A study demonstrated the use of propolis as an alternative therapy for wound healing to promote wound closure, especially under conditions such as human diabetic foot ulcer (DFU) [104].

The molecular mechanisms responsible for the wound-healing activity of propolis is shown in . Fibronectin (FN) is a multifunctional glycoprotein of high molecular weight, which influences the structural stability and functional properties of various organs and tissues (Stoffels, 2013). The fibronectin matrix and its accumulation are essential for cell migration, cell proliferation, cell differentiation, cell adhesion, apoptosis, cellular signaling, angiogenesis, collagen biosynthesis, re-epithelialization, clot formation, and platelet activity. Fibronectins are also important in the repair mechanisms for conditions such as glycoprotein intensified degradation, which leads to a defective cellular microenvironment and affliction in the structure of granulation tissues. This condition may prevent the wound from healing or inhibit the repair process. The accumulation of fibronectin in the extracellular space also modulates the secretion of other repairing components such as collagen type I and type III, tenascin, laminin, and fibrillin.

Molecular mechanism targeting wound-healing activity of propolis.

Propolis has demonstrated favorable effects in the wound-healing process such as antifungal and antibacterial activities due to its components such as flavonoids, phenolic compounds, terpenes, and enzymes. It also reduces the activity of free radicals (ROS) in the wound bed favoring the repair process. Propolis has also demonstrated great effects on collagen metabolism by increasing the amount of both type I and type III collagens in tissues. The reduction of ROS and accumulation of collagen aid in balancing the extracellular matrix and generating granulation tissues. Propolis is a potential apitherapeutic agent that is able to modify the metabolism of fibronectin by developing a fibrous network of extracellular matrix and inhibiting fibronectin disintegration. The active components in propolis such as quercetin and resveratrol inhibited fibronectin biosynthesis and TGF-dependent production of fibronectin, respectively, in C2C12 myoblasts. Both the components play important roles in regulating the expression of fibronectins. Studies have also shown that mobility and migration of epithelial cells are dependent on reduced fibronectin content in the extracellular matrix. Reduced amounts of this glycoprotein in propolis effectively treated wounds and produced granulation tissues. Therefore, the influence of propolis on fibronectin metabolism may alter the mechanism of wound healing [103]. Several health benefits of propolis related to gastrointestinal, gynecological care, oral health, skin care, and oncological treatments are tabulated in .

Selected propolis activities according to the health benefits.

Royal jelly is one of the honey bee products which have potential towards various human disease treatments. depicts the biological activities of royal jelly as an antioxidant, antitumor, antiaging, neurotropic, and anti-inflammatory agent.

Different types of biological activities of royal Jelly.

A randomized clinical study has reported that royal jelly is effective in reducing premenstrual syndrome [105]. A randomized clinical trial study reported the effectiveness of royal jelly in treatment of urinary problems and promotion of life quality in postmenopausal women [106]. Royal jelly has protective effects against Oxymetholone-induced reproductive toxin (OXM), which is an active steroid derived from testosterone as a defense mechanism. Recent studies have reported that royal jelly protects against the oxidative injuries in the mouse testes and that it contains spermatogenesis-stimulating compounds, which inhibit the production of proinflammatory cytokines [107]. Another study on male rabbits has indicated its positive effects on fertility, semen quality and output, and concentration of testosterone, total proteins, and glucose in the blood. The number of dead and abnormal sperm decreased with the reduction of biomarkers of oxidative stress [108]. Royal jelly has been traditionally used to treat menopause symptoms by rebalancing the hormonal concentration in the blood, decreasing follicle-stimulating hormones (FSH) and increasing the estrogen concentration in aged mice. A study showed that the changes in hormone levels resulting from royal jelly increased the amount of ovulated oocytes and their quality in aged rats [109].

The molecular mechanisms responsible for the antiaging activity of royal jelly are shown in . The quality of oocytes decreases with age and the depleted follicle pool hastens hormonal dysregulation. This hormonal dysfunction is responsible for the reduction in ovarian follicle size and oocyte quality. Oxidative stress is the main cause of aging. Increased oxidative stress and continuous ovulation causes loss of antioxidants such as SOD, catalase, and glutathione S-transferase (GST). It also minimizes the size of the follicle pool and oocyte quality. Oxidative stress is controlled by glutathione (GSH), glutathione S-transferase (GST), Glutathione S-Transferase Theta 1 (GSTT1), Bax, and Bcl-2. GSH, GST, and GSTT1 are direct ROS scavengers, which play a vital role in removing oxidative stress from the cell. Higher expression of Bax and lower expression of Bcl-2 also promote aging and reduces oocyte quality.

Molecular mechanism responsible for the antiaging activity of royal jelly.

FSH and luteinizing hormone (LH) are the hormones involved in the aging process. The amount of FSH and LH is controlled by estrogen (E2) and inhibin from the ovarian cells. Reduction of the follicle pool size results in an inadequate release of estrogen and inhibin, which results in a rise in FSH levels. This process then aids in the reduction of the follicle pool size and affects oocyte quality. This process promotes aging in the ovaries. In young ovarian cells, higher amount of estrogen (E2) and inhibins are needed to decrease the level of FSH and LH. This adaptation can be overcome by antiaging therapies such as supplemental consumption of royal jelly. The major active component present in royal jelly is 10-hydroxyl-2-decenoic acid. This compound enhances the synthesis of ovulation hormones, maintaining a lower expression of FSH and LH in young ovarian cells. It is also efficient in preventing the depletion of follicle pool and in enhancing hormonal regulation. Thus, royal jelly helps in preventing the aging process and is an influential antiaging product [109].

Poor mental state and performance such as in the case of Alzheimer's disease (AD) are mostly experienced by elderly individuals due to aging. Royal jelly stimulates physical and mental functions for the elderly and increases their appetite and weight. A study showed that royal jelly exerted neuroprotective effects in AD [110]. The behavioral and neurochemical effect of royal jelly was chemically examined in aged rats. The study confirmed a better cognitive performance and increased the life span in the older animals that had been given royal jelly. Another study reported that royal jelly contains longevity-promoting factors and extends the lifespan in the nematode Caenorhabditis elegans [111]. Another study have also reported the improved mental health in human upon ingestion of royal jelly for six months [112]. A few studies on the health benefits of royal jelly are given in .

Reports on health benefits of royal jelly.

Royal jelly enhances wound-healing activity. In both in vivo and in vitro wound-healing models, under the effect of royal jelly, human fibroblasts were able to migrate and increase levels of sphingolipids by decreasing the secretion and formation of collagen. Thus, royal jelly shortened the curing period of desquamated skin lesions [113]. Another study on the use of royal jelly have also exhibited protective action on human skin against ultraviolet B-induced photoaging by promoting collagen production [114]. Royal jelly dressing is also an effective way of treating diabetic foot ulcers besides standard treatments. This is due to its vasodilation effects around the affected wound, which can help to dilate the blood vessels to enhance blood flow. It also helps to prevents infections due to its antimicrobial activities [115].

The present review focused on the potential health benefits of bee products such as honey, propolis, and royal jelly. These products are highly rich in active components such as flavonoids, phenolic acid, phenolic compounds, terpenes, and enzymes, which have biological functions in preventing some diseases and promoting good health. Honey, propolis, and royal jelly have distinct efficacies with significant nutritional properties and functional values. Thus, these bee products can be developed into potent apitherapeutic agents. However, some precautions need to be taken in case of allergens associated with bee products and in finding the right intake dosage. Hence, it is necessary to conduct further studies to determine the critical mechanisms related to the pharmacological activities of these bee products and the appropriate amounts that can be taken in order to obtain promising health benefits.

The authors acknowledge the financial supports from the Research Acculturation Collaborative Effort (RACE) (R/RACE/A07.00/01147A/ 001/2015/000237) and a research university team grant (RUT) (1001/PPSP/853005).

The authors declare no conflicts of interest.

Originally posted here:
Honey, Propolis, and Royal Jelly: A Comprehensive Review ...

For many (albeit not all) the future of longevity is now; we are already living longer. According to the U.S. Census Bureau, the number of Americans living into their nineties is expected to quadruple by 2050. Demographers predict that as many as half of todays 5-year-olds can expect to live to the age of 100 in the United States. A century-long life will be a reality for more and more of us, so Id argue that anyone who equates increasing age with decreasing quality of life (and contribution!) read on and discover how to activate your potential leadership and impact. No generation before us has had the potential to experience the benefits of increased longevity, sustained vitality and the capacity to consciously curate decades of a meaningful life.

The Stanford Center for Longevity (SCL) has done extensive and exciting work in this very area. With breadth of cross-disciplinary research and ongoing data collection, SCL addresses the how question at the meta-level looking globally and structurally at policy and infrastructure changes necessary to support our longer lifespans in equitable ways. SCLs recently published The New Map of Life navigates us toward new models of all the nitty-gritty things that will need to be updated and radically shifted: education and lifelong learning; redesigning how we work; developing new policies for health care, housing, the environment, and financial security. Im proud to support the big picture shifts that need to happen through my involvement on the SCL Advisory Council. All of us are stakeholders and leaders, from wherever we are, in the seismic shifts outlined by The New Map of Life.

Both the New Map of Life and my formula for a life well-lived share an understanding that longevity is not simply a measure of the quantity of years or Lifespan, but it is about the quality or Healthspan of those years. A burgeoning medical specialization known as Lifestyle Medicine is the systematic practice of assisting individuals and families in adopting and sustaining behaviors that can improve health and quality of life. Were all familiar with the idea of preventative care, so why is it significant that our tradition-bound medical system has developed this new area of study and practice? Its not only because five of the seven leading causes of death in the US can be attributed to chronic, lifestyle-related conditions. Lifestyle medicine recognizes that your physical health, emotional wellbeing, and the accumulated effect of your daily lifestyle choices are inextricably linked.

Health and wellness has become a multi-trillion-dollar industry, with estimates reaching over 8 trillion in just a few years. With everything from Pelotons, FitBits, supplements, fad diets, and far too many other options to mention, embracing responsibility for your health while sifting through the massive information available can feel daunting and is often unnecessarily expensive. However, cultivating your health and wellness doesnt require expensive participation in that behemoth industry. Chinese philosopher Lao Tzu once said, a journey of a thousand miles begins with a single step. Your health and wellness journey can start today, and Im here to simplify it. In the Five to Thrive process, I unpack the building blocks that ancient traditions and modern research agree bolster your health and wellness. Take the free assessment from which you can create your own micro-ambitious plan.

As our recent Facebook quiz taught us, what makes a 100-year life worth living is when it is imbued with an ability to remain independent, with a sense of community, meaning, purpose and joy. To me, the discussion of longevity boils down to this: a life well-lived is not only measured by the number of healthy years you live but by whether or not you thrived in those years. And as social scientists from Victor Frankl to Brene Brown have proven time and again, without a sense of purpose and a capacity to love and be loved, we fail to thrive as humans.

Purpose and the deeply catalyzing force of love ground and propel every single one of us. Purpose, love and connection are central to my work as a leadership coach and a consistent element of what separates the good from the great. So, if we consider any formula for longevity seriously, a sense of purpose and love that bring meaning to this thing called life are required ingredients. You can cheat on a diet, you can get away (for a while at least) without daily exercise, but you cant shortchange your spiritual and emotional health for long without serious consequences.

Resilience is the bounce-back factor, the capacity to prevail in the face of stressors outside your control. Resilience means aiming for a sense of realistic, holistic alignment that is not contingent on your body being perfect or pain-free, unmarred by time, but extends beyond the physical and mental, and into spiritual wellbeing as well. Its so challenging to cultivate resilience in light of the diet of success stories and routes to that success which weve been fed since our childhood. It goes like this: study hard, work harder, make the right connections, prove yourself, do it again. The underlying expectation has been that this recipe will cook up a smoothie of success for life. Yet, life is not a linear path towards ever-ascending destinations. Its a journey that unavoidably hits detours through mountains and valleys. Those of us who understand and regularly practice strengthening our physical and psychological resilience are those with the right ingredients for a life well-lived. So yes, if were talking about living toward 100, resilience will be required. Lots of it!

I love the way the Stanford Center for Longevity frames aging as a longevity buffet with servings of time. This begs for the question: what are you hungry for? Ignore the ageist memes and other cultural tropes that result in our missing out on the wisdom of our elders and suffering for that loss. You are needed now, perhaps more than ever. What the world needs now is not only love, sweet love, but wisdom, courage, experience, and a spirit of wanting to do the right thing for the sake of simply doing the right thing.

Originally posted here:
The Future of Longevity is Now: How to Live and Lead to 100 - Thrive Global

Its red, squishy and works non-stop to keep everyone alive. Its not the latest political pundit but the human heart.

The continuously pumping organ is responsible for moving blood throughout the human body, supplying oxygen and nutrients and removing toxins and waste. Weighing between 8 and 12 ounces, the heart is a mighty organ divided into four chambers that work together to pump blood in and out.

The heart gets oxygenated blood from the lungs and pumps it throughout the rest of the body. It does this by contracting at a rhythmic pace, about 60-80 times per minute, thanks to electrical cells called pacemakers.

February is National American Heart Month and brings focus to the muscles function, role and how individuals can maintain a healthy life for heart longevity.

Dr. Arie Szatkowski is the Medical Director of the Baptist-Stern Joint Venture that oversees the cardiovascular services for the Metro Baptist Hospital System. He detailed several symptoms of heart issues that older adults should be aware of through their later years.

Cardiovascular disease affects most men and women as they move through the last several decades of their lives, Szatkowski says. One out of three of us, cause of death is a cardiovascular one. As we get older a lot of things change. Our vessels become stiffer and other biological changes to our circulatory system. Our heart functions have some changes to it that led to a decline in the way our heart relaxes, the way our blood vessels respond, the way our heart rates respond.

In spite of all these changes Szatkowski says people are living a lot longer.

One reason is that medicine has helped, people are taking care of themselves better, Szatkowski says. The ones that do can certainly live longer. As a result of living longer, more elderly folks are getting to the doctors office to maintain their health.

Symptoms to be aware of include a buildup of plaque which can lead to fatigue from general, everyday activities.

Plaque in the arteries can cause a reduction of blood flow to a part of the heart, Szatkowski said. There are two ways people would experience discomfort from such a thing. One would be a gradual increase in symptoms during activities. If you're fairly active and still participate in daily activities like gardening, household chores or going for walks everyday, you might notice a discomfort in your chest when you increase your activity level. That could be a pressure, tightness, squeezing, it could feel like indigestion, it might radiate to your jaw, you might be short of breath, fatigue might set in. These symptoms usually occur repeatedly, not just a one-time occurrence.

Those indicators are reasons to go see your physician as soon as possible.

If that happens, just be sure that it isnt anything else, said Dr. Szatkowski, who is also the acting president of the Medical Staff at Baptist Desoto Hospital and director of Cardiovascular Services and Echocardiography lab at Baptist Desoto Hospital. In modern times, were able to treat many types of diseases for folks, even into their 90s.

Cardiac symptoms like blocked artery, valve issues or heart failure often present with exertional fatigue. Senior citizens may decide to minimize physical activity because of the perceived tiredness. They may convince themselves, Im just getting older, I cant do what I used to do, or Im not as young as I used to be.

Even the simple act of needing to sleep at night with several pillows to lay on could be an indicator.

If you have the inability to lay flat because you get short of breath, thats oftentimes a sign of heart failure, said Dr. Szatkowski. If you sleep with a lot of pillows, because if you lay flat you get winded or wake up in the middle of the night gasping for air, those are signs that require attention.

According to the Centers for Disease Control (CDC) about half of all Americans (47%) have at least 1 of 3 key risk factors for heart disease: high blood pressure, high cholesterol, or smoking.

High blood pressure, if not controlled, can affect your heart and other major organs of your body, including your kidneys and brain.

Cholesterol is a waxy, fat-like substance made by the liver or found in certain foods. Your liver makes enough for your bodys needs, but we often get more cholesterol from the foods we eat.

If older adults take in more cholesterol than the body can use, the extra cholesterol can build up in the walls of the arteries, including those of the heart. This leads to narrowing of the arteries and can decrease the blood flow to the heart, brain, kidneys, and other parts of the body.

Tobacco use increases the risk for heart disease and heart attack. Cigarette smoking can damage the heart and blood vessels, which increases risks for heart conditions such as atherosclerosis and heart attack. Nicotine raises blood pressure and carbon monoxide from cigarette smoke reduces the amount of oxygen that your blood can carry. Exposure to secondhand smoke can also increase the risk for heart disease, even for nonsmokers.

The CDC has more resources and information about heart health and heart disease prevention at http://www.cdc.gov.

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Know the signs for heart health issues and see your doctor regularly - DeSoto Times-Tribune

Bubbles are more scientifically complex than one might think. The popular children's activity of blowing bubbles can teach researchers about evaporation. A new study published in Physical Review Fluids marks an exciting milestone in bubble technology. A team from the University of Lille in France created a bubble from a composite liquid film which lasted a whopping 465 days before popping.

Typical soap bubbles rarely last longer than a minute in the open air. These pockets of air are delicate and held together only by the surface tension of a thin film of soapy water. As the water in that film evaporates into the surrounding atmosphere, it can no longer sustain the surface tension. The fragile orb then pops. Defeating this drying effect of evaporation is key to making a hardier bubble, researchers have discovered.

One type of hardier bubble is known as a gas marble. Like a regular marble, it can be rolled around and held in one's hand. These stronger bubbles are made of a composite liquid film. Tiny plastic beads are used to reinforce and strengthen the thin film surrounding the air pocket. To study the longevity of these gas marbles, the University of Lille team created two kinds: one using water as a base, the other using water-glycerol. Glycerol is a compound found in soap which bonds well with water molecules.

The team compared these two types of gas marbles with regular soap bubbles. The regular bubbles popped quickly, but the water-glycerol bubble lasted over a year. Its 465-day lifespan is a world record for any bubble, earning it the nickname everlasting bubble. The team credits the glycerol in the bubble for absorbing water and preventing evaporative drying, among other advantages.

Such anti-evaporation technology may be useful in medicine, says New York University professor Leif Ristrophwho was not involved in the study. He told NBC, Im daydreaming here, but I could imagine it might be useful to armor little droplets in aerosols and sprays to make them last longer in airFor example, some sort of medicine thats administered by spraying and breathing in the aerosol.

h/t: [Futurism, Wired]

Ethereal Portraits of People in Bubbles

World Landmarks Reflected in Bubbles (10 photos)

Spectacular Photos of Bubbles Frozen in Frigid Temperatures

Breathtaking Frozen Bubbles Look Like Elegant Glass Ornament

More here:
An "Everlasting Bubble" That Lasted 465 Days, Then It Popped - My Modern Met

There is a breadth of knowledge currently available about nutrition and health, but we can all agree on one very fundamental truth: what you put in your body matters. After pouring through a variety of studies and articles and opinions, that much is clear. Food is medicine, and as with any medicine, it can power your body to do incredible things.

For example, food can even help you live to be 100 years old. As of 2021, over 70,000 Americans have celebrated their 100th birthdayand it turns out, what they eat matters more than almost anything else. The Blue Zone project has done research on just how centenarians do it, focusing on five "blue zone" communities where people have the most incredible longevity in the world.

From the Nicoya Peninsula in Costa Rica to Okinawa, Japan, the people in these communities all share a variety of behaviors that increase their lifespan. Community, mindset, and movement are important. But there is no match for the power of the food they nourish themselves with. We dug in deep and rounded up the top five eating habits that centenarians share.

We've heard of the 80% kitchen, 20% gym rule before, but this is a different 80% guidelineone that dates back 2,500 years. Apparently, it is tied to a Confucian mantra that is called "hara hachi bu" in Okinawa, and it is a reminder to stop eating when you feel like you are 80% full. As the Blue Zone project puts it, "the 20% gap between not being hungry and feeling full could be the difference between losing weight or gaining it."6254a4d1642c605c54bf1cab17d50f1e

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Depending on your eating hours, intermittent fasting may be a version of this tactic. The idea here is that as it gets later in the day, the human body should consume fewer calories. In the Blue Zones, people tend to eat their smallest meal lastand not very late at nightand then don't eat for the rest of the day. Great news for those of us who like big breakfasts!

Beans, beans, the magical fruit. Apparently, their magic extends all the way into life expectancya bean-rich diet is the core of most centenarian lifestyles. This can mean fava beans, black beans, and even soybeans and lentils. For more on just how healthy beans really are, check out our research on the Secret Side Effects of Eating Beans.

Perhaps this is less surprising, given the increasing societal shift away from meat towards plant-based diets. On average, people in blue zones eat meat only five times per month. The detail that might shock you, though, here? The primary kind of meat consumed is pork.

Here is another hack that has been widely promoted across many health channels, but the centenarians confirmed it: serving size is, in fact, key. According to the Blue Zone Project, serving sizes are typically kept between 3 to 4-ounces, which is about the size of a deck of cards. To get a handle on serving sizes, here are 18 Easy Ways to Control Your Portion Sizes.

Kaley Roberts

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5 Eating Habits You Should Know from the World's Longest Living People Eat This Not That - Eat This, Not That

Norman Swan: Hello, Norman Swan here with this week's Health Report. Life expectancy has been rising about three months a year since the mid 19th century. We do well in Australia and are usually in the top five or six most long-lived nations. When we personalise this to the individual although, life expectancy, which is a national average, becomes irrelevant. What many of us really want to know is how long we are going to live and how much of that will be in good health. Living longer is an obsession and there are pills galore being offered to slow ageing and maybe even reverse it. Even so, the increase in longevity may be stalling, and you've heard a lot about that on the Health Report over the last two or three years because our metabolic health is declining and our abdominal girth is increasing.

So what works in slowing ageing? Well, that's been the life work, at least so far, of Luigi Fontana, an international authority on the biology of ageing and the dietary interventions, especially calorie restriction, which in fact is what many of the anti-ageing pills seek to emulate without having to cut back on what you eat. Luigi Fontana is Professor of Medicine and Nutrition and has a chair in translational metabolic health at the University of Sydney, and I spoke to him recently at length.

Luigi Fontana: When I was a medical student we had a professor in geriatrics who gave a very interesting lecture about the effects of dietary restriction in mice being the most powerful intervention to extend lifespan and health span. And so I was fascinated. I said, ah, so there is something in mammals that is able to extend lifespan up to 50%. It is like for human beings instead of living 80 years, to live 130, 140 years. The data back then, so we're talking about 25 years ago, were showing also a huge increase in health span with the prevention of cancer, cardiovascular disease and kidney disease, autoimmune diseases

Norman Swan: And before you go on we should just define our terms here. So, lifespan, just crudely, is how long you live, it's not life expectancy, it's just the absolute number of years you have on the planet, and health span is how many healthy years you've got before disability and other diseases start to encroach on your life.

Luigi Fontana: Absolutely. I wasn't happy with being a practitioner where you go to the emergency room because there is a patient with a myocardial infarction, a stroke, and you try to minimise the damage. I said, is it possible to understand if humans, like animals on calorie restrictions, they live at least healthier and possibly longer if we can slow down ageing and accumulation of damage? And so I started to search and there was nothing in humans

Norman Swan: And the important caveat here isit's bloody obvious when you think about it, but mice are not humans, although dietary restriction does spanthey've shown it in fruit fly, in yeast, in other animal species.

Luigi Fontana: In monkeys now, rhesus monkeys.

Norman Swan: But the holy grail is humans because humans are a lot more complicated.

Luigi Fontana: Just to give you an example, mice or rats, they live on average 2.5 years, human beings live on average for 80 years. Rhesus monkeys, they are primates, they live on average 26, 27 years. So even if they are primates, they live a third of what a human being nowadays lives. And so basically I decided to search and I discovered that there was a Professor John Holloszy in the US at Washington University who was starting a program on calorie restriction in humans, and he replied to me and said, come on, come to the US. So I took my luggage and then I fell in love with what I was studying. John, he just died a couple of years ago, was one of the guys who discovered that exercise increases mitochondrial biogenesis, is improving insulin sensitivity, preventing diabetes. So he was a brilliant mind, a pioneer.

Norman Swan: And we will come back to mitochondrial biogenesis in a minute because these are the energy sources in the cells, possibly the source of ageing, and regenerating, revivifying these mitochondria might be one of the answers for delaying ageing.

Luigi Fontana: Exactly. And I spent the next 17 years working on humans, research on calorie restriction. So we studied people who were practising calorie restriction, so what is called technically a cross-sectional study, you compare these people with people who are master athletes or sedentary men and women consuming Western diets. And then we did two big randomised clinical trials, the calorie where we randomised people on calorie restriction. The first one, the step one calorie randomised clinical trial was comparing people randomised to 25% calorie restriction without malnutrition, so with all the vitamins and minerals.

Norman Swan: So what with the outcomes you were looking for, because you can't hang around for 90 years to see whether or not they live longer.

Luigi Fontana: Exactly, so lifespan is impossible. Even in monkeys, the monkeys study now we have finished 20 years to get data on survival, and so it's feasible but for humans it's impossible. In terms of longevity what we are trying to do is to develop biomarkers of ageing, what is called biological ageing, can we measure biological age and with some biomarkers. Right now the most common one, the most trendy one is epigenetic ageing. So you measure DNA methylation, and there are some DNA methylation clocks that are

Norman Swan: So, just to explain, epigenetic changes are not mutations in the actual DNA, they are chemical reactions around the side of the spiral, the helix, which changes its shape and changes its function. And this DNA methylation that you are talking about is one of these chemical reactions that changes the shape, for better or for worse.

Luigi Fontana: Yes, exactly, and so basically these epigenetic changes is basically the regulation of which part of the DNA is translating into proteins. And what we have discovered is that what you do in your life, what you eat, if you exercise, if you smoke, if you are stressed, is changing the transcription of DNA. And new data is suggesting that as you age, basically there are changes in this transcription

Norman Swan: Which may well measure your clock as opposed to how many days or months you've been on the Earth, it's really how many days or months it affects your biology.

Luigi Fontana: Exactly, you can compare basically your chronological age, how many months and years you've been living, compared to the biological age. So you can be biologically younger. Let's say you are 50 years old, biologically you are 40, or biologically you are 60. And so these are experimental tools that we are training, that we are working on, and it looks like they are good. And so ideally we hope that in the next few years we are going to refine these biomarkers of biological age and then we can do an intervention, it can be exercise, it can be diet, it can be a supplement, it can be a drug, and we can say, okay, your body has rejuvenated. Or if you are smoking or if you have other unhealthy lifestyles, you have been getting older than your chronological age.

Norman Swan: And what about the telomeres? We've spoken about that a lot on the Health Reportby the way, you are listening to the Health Report on RN with me, Norman Swan, and I'm speaking to Professor Luigi Fontana, world authority on ageing, slowing ageing, the biology of ageing. So we've spoken about the telomeres, these bits on the ends of the chromosomes, almost like the plastic bits on your shoelaces, to protect the chromosomes which get shorter as you age, as each cell goes, and also if you seem to have less damage of ageing they seem to be longer. Are they good as markers for ageing?

Luigi Fontana: Look, we don't use them in our research. In the past there was a lot of hope that good biomarkersbut Elizabeth Blackburn who got the Nobel prize for telomere and telomerases, she is a friend, and I sent her some samples of these people doing calorie restriction, and we don't see changes. And even in animals on calorie restriction we are not able to use those as a biomarker. It doesn't mean that what you just said, that as you age, every time the cells are dividing or replicating the telomere gets shorter. So, no doubt about it, it's real. I'm just saying that

Norman Swan: It's not a good clock.

Luigi Fontana: Exactly.

Norman Swan: So, come back to the trials now; what do the trials show?

Luigi Fontana: So the first one we compared people who were doing 25% calorie restrictions without malnutrition, or people who were exercising to increase their energy expenditure by 25%, and then we had the control sedentary group. And we found that of course they were leaner, they had less visceral fat. Interestingly, both the CR and exercisers lost around 9% of their body weight, and 40% on average of their visceral fat.

Norman Swan: The dangerous fat in your tummy.

Luigi Fontana: Yes, the dangerous abdominal fat. And then we found improvements in inflammation, reduction of inflammation, we found improvement in insulin sensitivity.

Norman Swan: And just again, so inflammation, which is really an overactive immune system which causes thickening and damage to your internal vessels, is probably part of the ageing process.

Luigi Fontana: Yes, inflammation now we know is a key factor in the development of cancer, cardiovascular disease, stroke and many other diseases, including ageing. So it's one of the major players in ageing and many chronic diseases. So we saw an improvement in insulin sensitivity. Insulin is very important, based on many animal models of longevity. So nowadays we can play with genes and we can knock down one gene or we can over-express one gene in rodents, and then we can look at what are the physiological or lifespan effects of these genetic manipulations. And so I will say that 80% of the animal models of longevity, meaning mice that are living longer than the wild type, they have a mutation in the insulin IGF-1 pathway, so they have less insulin biding, less insulin transduction. And what we know is that as you get older, especially as you accumulate belly fat, visceral fat because you are in a positive chronic energy balance, you are becoming insulin resistant. So there are a number of hormones produced by the adipose tissue called adipokines that are making the skeletal muscle but also the adipose tissue and other cells resistant to the effects of insulin.

Norman Swan: And you get growth hormones that can stimulate cancer, so a lot of focus is on insulin, it's much more than diabetes in terms of how it affects the body.

Luigi Fontana: Yes, a lot of people think about insulin when they talk about diabetes. In reality, before you become diabetic you have many years of insulin resistance and hyperinsulinaemia. So the beta cells of the pancreas that are the cells that are producing insulin, they are trying to over-produce insulin to overcome the peripheral insulin resistance, and this hyperinsulinaemia is driving cancer and ageing.

Norman Swan: So, high levels of insulin.

Luigi Fontana: Yes.

Norman Swan: So you've got a signal that reducing calories by 25% seem to be doing similar stuff to

Luigi Fontana: Exactly, so if we have to summarise what we did find, many of the metabolic hormonal adaptations that we have described in long-lived dietary restricted animals are also occurring in humans. So humans are adapting to calorie restriction similarly to animals. Another important one, we found a major reduction in oxidative stress markers, biomarkers like F2-isoprostanes.

Norman Swan: This is biological rusting, which goes along with inflammation and drives those mitochondria that we were talking about as well.

Luigi Fontana: We also saw an increase in autophagy proteins in genes. Autophagy is another important mechanism.

Norman Swan: So again, to explain, your cells get old and they should die but some cells don't die and they just sit there causing havoc and you want the body to get rid of them

Luigi Fontana: But that's senescence. Autophagy is different. So as we get older, we have accumulation of garbage in our cells because our cells are becoming less efficient to remove misfolded proteins, old mitochondria, so mitochondria that get oxidised, they become dysfunctional, and so if you are in energy restriction, the cells, they are trying to say, okay, now where do I get the material to create energy for cell functioning, and they start to digest the garbage, and so that's called autophagy.

The other factor we found in humans as well is what you are saying before, cell senescence. As we get older, we have an accumulation of DNA damage, and when you have accumulation of DNA damage that can be stimulated by smoking or radiation and many other stuff, you have two different options. One is this DNA damage ends up in oncogenes, you have cancer. Otherwise, this DNA damage can cause cell senescence. And what other colleagues have found is that these senescent cells, these old cells, these zombie cells, they are producing pro-inflammatory cytokines. So this is a major source of inflammation itself. They are also secreting pro-cancer factors, and we found that in humans and in animals on calorie restriction, there is a reduction in senescent cells.

Norman Swan: So, popular books out there being sold as the solution to ageing, and I'll declare a conflict of interest here as I've got one coming out in August, but hopefully reasonably scientificlet's just take fasting. So, fasting has been touted as the answer here, and what they do is they say, look, if you look at fasting in animals it prolongs their lifespan, it emulates dietary restrictions. So if you look at the chemical pathways, I'll just use some technical terms like SIRT1, they recapitulate that and work in the same way. So what's your view on fasting as a surrogate for dietary restriction?

Luigi Fontana: The story of fasting, really at least the commercial part, started with the Michael Mosley documentary Eat, Fast and Live Longer, I was one of the two characters on the documentary, and he came and interviewed me in St Louis and then he interviewed Valter Longo in Los Angeles. And back then he put together a nice story, but without scientific data because there were no human studies. And even right now, the data on the effects of fasting, intermittent fasting or time restricted feeding in humans, the data are very, very slim. I'm talking about humans. In animals, yes, the data are overwhelming that intermittent fasting is extending lifespan and health span.

Norman Swan: But isn't there evidence in humans and larger animals that it increases ageing, speeds it up?

Luigi Fontana: No, but we have dataI shouldn't talk about it but I'll give you justwe have a paper submitted now in a major journal for publication, and we were able to do intermittent fasting for six months plus six months, and we see a beautiful reduction in body fat, in body weight and body fat, 8% weight loss, so it's very good for the standards of calorie restriction, but we don't see improvements in inflammation, no improvement in inflammation, a very tiny improvement in insulin sensitivity in many factors. So despite the fact they lose the same amount of body weight that we achieve with classical calorie restriction or with exercise, metabolically we don't see the same responses. Why? Well, what we are finding is that a calorie is not a calorie, that the quality of the food you are eating influences the metabolic response to weight loss, okay? So the shortcut that many think, okay, you know

Norman Swan: So if you're having bacon and eggs, it's not the same as a Mediterranean diet.

Luigi Fontana: Exactly. It's a balance between exercise, the amount of calories you are burning and the metabolic adaptations that you are triggering with exercise, the quantity of calories and the quality of those calories, they are three pillars. Before we were discussing about these easy-fix types of books or solutions that are very, very trendy, it's like if you go to the director of a symphony orchestra and you say, 'Tell me, what is the most important instrument in the symphony?' I don't know, he likes violin or cello. Okay, now I create an orchestra only with violin

Norman Swan: It's funny you should say that, actually one of my chapters in my book says anti-ageing is orchestral.

Luigi Fontana: Exactly, we agree. So to have a beautiful symphony, I don't know if you like Shostakovich, whatever symphony, or Mahler or Beethoven, you need a balance of all the instruments. If you have an overwhelming violin section, then you kill the beauty.

Norman Swan: So then this translates to the individual substances that people say can influence the pathway like resveratrol or NAD boosters, Fisetin and so on, they should work but they don't when you actually study them.

Luigi Fontana: That's what is coming up, that basically in experimental animals some of these molecules, not the ones you mentioned but, for example, rapamycin and others, they are extending lifespan, but we know, for example, that rapamycin in humans is causing type 2 diabetes, is causing immune depression. So if you are mice who are living in a pathogen-free facility, well controlled, in an environment where you are not exposed to viruses, to bacteria, then it may work. But if you are living in an environment like we do, where there is Covid and influenza and bacteria, then you know some of these molecules are dangerous.

Norman Swan: One of the things I'm interested in is the concept of homeostasis. So homeostasis, just to explain to the audience, is this balance. You talk about the balance in the orchestra and you talk about rapamycin, which is a fascinating substance discovered on Easter Island and taken back and having all these effects and used in people with kidney transplants to stop rejection and so on, is that when you look at ageing, some people would argue that ageing is a disruption of homeostasis, so we have a balance, and the balancesay we don't eat well, we don't get much exercise, we put on weight, the balance just tips towards ageing. So it's like the leaning Tower of Pisa, to use an Italian metaphor. So you have this leaning Tower of Pisa, and then what happensso I'm putting a hypothesis to you, is that when you try and correct the leaning Tower of Pisa to vertical, the whole body wants to push it back to a leaning situation because the body knows it needs a balance. If you are laying down protein and making substances, you've also got to break it down. If you put down fat, you've got to be able to lift it up and use it for energy. And so it's very hard to shift that balance. Does dietary restriction restore the disrupted homeostasis of ageing, so, in other words, the leaning Tower of Pisa?

Luigi Fontana: It looks so, even if the sooner you start calorie restrictionso the classic experiments shows that if you start dietary restriction without malnutrition, and let me reinforce that, 'without malnutrition', so going back to the day of fasting where people say, okay, I fast a couple of days per week and five days a week I eat whatever I want. That is dietary restriction with malnutrition. But in the experimental models we found that if you start 30% dietary restriction in a very young animal, typically we were starting in post-weaning mice, you have an extension up to 50% of lifespan. If you start the same 30% dietary restriction in a 12-month-old mouse that is equivalent probably to a 40-, 50-year-old human being, you have a 15%, 20% increase in lifespan because in those 12 months that is like 40 years for a human being, you have accumulated damage. And yes, you can undo some of the damage but not all of it.

So the message is that at any age you can improve your health by exercising, changing your diet, counting your calories, controlling your calories, the quality of what you eat, but you cannot go back totally to the same effects of when you started calorie restriction when you were younger. So the message is that the sooner you start to counteract the damaging effect of ageingbecause, as you said, ageing is a mechanism where the repair mechanisms are getting old. When you were young you have a bone fracture and you're going to repair very quickly, when you are 70 years old you have a bone fracture, you are not repairingif you have a scar when you are young, you are able to repair very quickly the scar, and when you get older, less, because all these mechanisms, this autophagy, DNA repair mechanisms, the antioxidant mechanisms, the removal of senescent cells, they get old and less efficient to keep homeostasis.

Norman Swan: But there is still an effect.

Luigi Fontana: There is still an effect. What I'm saying is that your trajectory of ageing is the deterioration of 20% of these mechanisms per year. If you eat unhealthy, if you have excess belly fat, if you are not exercising, if you are smoking, if you are over-drinking, you are accelerating the accumulation of damage and the deterioration of these mechanisms instead of if you are exercising, you are eating well, you are eating good quality, you are eating the right amount of calories, you don't gain too much belly fat as you get older, you are decelerating these mechanisms and in some cases you are rejuvenating cells.

Norman Swan: So do you live in a monastic lifestyle then?

Luigi Fontana: No, I think it's noteverything dependsfor example, I exercise I would say one hour, probably 5 to 6 times a week, and here in Sydney it's beautiful because the weather is so nice all year long, that even in the winter, even at 6pm I take my bike and I go for an hour and for me it's refreshing. After one day using my brain, going on a bike, it's beautiful. So, one hour a day out of 24-hours is not a lot.

And then I eat a very healthy Mediterranean diet, so very colourful, very tasty, with a lot of fresh fish and here in Sydney we are blessed, lots of different types of vegetables, whole grains and beans, so I have a range ofI think my diet is more diverse than many Australians and Americans because I have a lot of different recipes, very tasty. So I control my calories in two or three ways. One is to eat a lot of unrefined food, so whole grains and beans and vegetables and fish, and in this way you are already controlling your calories. We did a study in the USagain, we haven't published it but I'll give you the results, we are writing the manuscript right now, where we fed people in a randomised clinical trial for two months a Mediterranean diet comprising basically whole grains and vegetables and beans and fish, poultry once a week only, for two months. But I asked my dietician to clamp the body weight. So if the participant was, let's say, 80 kilos at baseline at the beginning of the study, I wanted the same person to be 80 kilos at the end of two months on this Mediterranean diet, you know, we provided the food.

Norman Swan: So they could see the pure effect of the diet rather than weight loss.

Luigi Fontana: Exactly, the results are going to be striking. But just to tell you the results, we had to over-feed people 250 calories to keep their body weight constant.

Norman Swan: You're kidding!

Luigi Fontana: Yes, and it was designed to be iso-caloric

Norman Swan: So it's hard work to maintain the weight.

Luigi Fontana: It was hard work, they were losing weight like crazy because the high-fibre diet compared to their typical American super-refined ultra-processed food, it was already able to make them lose weight like crazy. So this is a simple trick. You think about calorie restriction like, you know, having these tiny portions, an empty plateno. I'm eating huge amounts ofif you look at my plates, huge and big salads, very colourful, tasty, I do my dressing with orange juice or lemon juice with pepper and this and that, a lot of spices, so you can be very creative. It's science-based, it's not just fiction. So that's number one.

And then the other one is stop eating when you are 80% full. How do you do that? Typically we prepare these big portions and we have this plate full of food, and typically you try to finish everything because otherwise you feel guilty

Norman Swan: As you are told by your grandmother, you had to do it.

Luigi Fontana: Yes, you feel guilty to leave something on the plate, instead of one trick is to do small portions on your plate, you do a small portion, then you know you are still very hungry, you need another small portion, until you reach a point where you say, maybe I would eat another three or four tablespoons but I'll stop, I'm satisfied enough, I have a tiny bit of hunger but I'm satisfied, and that's a way to restrict your calories, the second one. Then, if you are overweight and you are trying to lose weight, then you can use a third trick which is basically fasting, vegetable fasting once or twice a week where you eat only

Norman Swan: Which is what the Greeks do.

Luigi Fontana: Yes, only raw or cooked vegetables, a wide variety, non-starchy vegetables, with a couple of tablespoons of olive oil per day because one tablespoon is 120 calories, and then you can use orange or vinegar, whatever you want. And the fourth one is eating everything in a window of six, eight hours.

So in this way if you put together high-quality plus fasting or this 80% filling, you don't have to be a monk orit's very easy, especially if you exercise, because we have clearly shown in these randomised clinical trials I was telling you about in the beginning, that if you lose weight, let's say 8% reduction in body weight with exercise or with calorie restriction, if you lose weight with calorie restriction you have a reduction in T3, triiodothyronine, it's one of the major active thyroid hormones. Therefore, you are lowering your resting metabolic rate. Whenever you are lowering your thyroid hormones

Norman Swan: So you are burning less calories, fewer calories at rest.

Luigi Fontana: Yes. Instead of if you lose the same amount of body weight and body fat by exercise you have no reduction in T3.

Norman Swan: So you balance the two.

Luigi Fontana: Exactly, so basically your metabolism is still very high, and therefore it's mandatory to always couple exercise with diet, otherwise you are lowering your resting metabolic rate, and then you are going to regainsooner or later you are going to regain all your body weight and body fat with the interests.

Norman Swan: Luigi, thank you, it's been fascinating.

Luigi Fontana: You're welcome, thank you for having me.

Norman Swan: We'll get you back when these results are published. Thank you very much.

Luigi Fontana is Professor of Medicine and Nutrition and has a chair in translational metabolic health at the University of Sydney. He has a book which came out in 2020, it's called The Path to Longevity: The Secrets to Living a Long, Happy, Healthy Life. This has been the Health Report, I'm Norman Swan.

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The lowdown on longevity - Health Report - ABC News

When it comes to weight loss, two diets may not be better than one. In a new study of people who cut calories to shed excess pounds, participants got similar results when they limited meals to certain hours of the day and when they ate anytime they wanted.

For the study, researchers randomly assigned 118 people with obesity to limit how much they ate for one year 1,500 to 1,800 calories for men and 1,200 to 1,500 calories for women. Half the participants were also asked to eat only between 8 a.m. and 4 p.m., while the rest of them could eat whenever they liked.

People who ate only during certain hours, a practice known as intermittent fasting, lost an average of 8.0 kilograms (17.6 pounds) after one year, compared with 6.3 kilograms (13.9 pounds) for people who only cut calories, the researchers reported April 21 in the New England Journal of Medicine. But that difference was too small to rule out the possibility that it was due to chance.

While weight loss was the main goal of the experiment, researchers also looked at several other outcomes that can be indicators of health problems for people with obesity, including waist circumference, BMI, proportions of body fat and lean body mass, blood pressure, and metabolic risk factors like blood sugar levels. Outcomes for all these indicators were similar with and without intermittent fasting, the study found.

The two weight loss regimens had similar results, says the senior study author,Huijie Zhang, MD, PhD, a chief physician, professor, and deputy director at Nanfang Hospital of Southern Medical University in Guangzhou, China. People can choose the most suitable weight loss approach according to their own preference and needs, Dr. Zhang says.

There are several caveats to these findings, however.

For one thing, the participants were generally healthy, making it harder to see dramatic changes in outcomes like blood pressure or metabolic risk factors after one year of new eating habits, says Blandine Laferrre, MD, PhD, the coauthor of an editorialaccompanying the study and a professor of medicine at Columbia University Irving Medical Center in New York City.

Beyond this, the participants already tended to eat over a fairly narrow window of about 10 hours and 23 minutes per day at the start of the study. This may have made it hard to see dramatic changes in weight loss when they were put on an intermittent fasting plan because it reduced their food intake period by only about two hours, Dr. Laferrre says. People who eat during more hours of the day at baseline are more likely to benefit from intermittent fasting.

In addition, the study participants got unusually good results from cutting calories, losing an average of 9 percent of their body weight. This may have blunted any effect from intermittent fasting, Laferrre notes.

The studyshows that the main driver of the weight loss was the calorie restricted diet, and not the time-restricted eating diet, says Krista Varady, PhD, a professor of nutrition at the University of Illinois in Chicago who wasnt involved in the study.

But this doesnt necessarily mean intermittent fasting is a bad approach to weight loss, particularly for people who struggle with typical means of cutting calories, such as by tracking everything they eat.

The main benefit of time-restricted eating is that you don't need to count calories in order tolose weight," Dr. Varady says. "Just by limiting the eating window to eight hours per day, people naturally cut out 300 to 500 calories per day.

And not all calories are created equal, says Lon Ben-Asher, RD, a nutritionist at Pritikin Longevity Center who wasnt involved in the study.

We should aim our focus on the quality of the food we consume by following our hunger and satiety cues, not the time of the day when we eat, Ben-Asher advises. In addition, we should concentrate our efforts on consuming more foods that create greater satiety per calorie, such as vegetables, fruits, whole grains and unrefined carbohydrates, beans, lentils, and other legumes which contain a high level of dietary fiber and water content.

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Why Intermittent Fasting May Not Help When You're Already Cutting Calories - Everyday Health

Kane Tanaka, a Japanese woman who shared a birth year with the likes of George Orwell, Lou Gehrig and Bing Crosby, passed away last week at the age of 119, as CNN reported. According to longevity researchers she was the second-oldest verified human being to ever live, and the oldest ever from a country thats famous for producing centenarians.

Tanaka had been in the news a bit in recent years she was poised to play a part in the Olympic torch ceremony ahead of the 2020 Summer Olympics in Tokyo, but her family and Games officials scrapped the plan once the COVID-19 pandemic arrived. (Many publications pointed out at the time that Tanaka was one of the few people on the planet to live through both the 1918 influenza pandemic which started when she was 15 and the coronavirus pandemic.)

She lived through quite a bit, in fact: two world wars, five Japanese imperial reigns, 21 American presidencies, a dramatic industrialization of her home country and unthinkable global population growth. At the time of Tanakas birth, there were fewer than two billion people living on the planet. That number is now up to nearly eight billion.

Tanakas life was local, quiet and remarkably consistent. She married at the age of 19 and worked in a family shop that sold udon noodles into the age of 103. (Her husband passed away at the age of 90, after 71 years of marriage.) Her last few years were spent in a nursing home, and according to her family, she was frequently sick over the last few months. She falls a little over eight months short of her recent goal to live to 120.

Its remarkable that Tanaka lived as long as she did, though, considering she suffered from a variety of serious ailments and illnesses over the decades, including paratyphoid fever, pancreatic cancer and colorectal cancer. Her life along with those of other so-called supercentenarians lends credence to latter-day scientific thinking that the human lifespan does not have a ceiling, but is actually heavily influenced by lifestyle and behaviors.

(Some scientists have suggested that ages 40 years above todays average life expectancy as attainable for future generations. And with future medicine, which will lean heavily on cellular reprogramming, theres no telling how long a human being could live. Is 200 years within reach? Many geneticists now say Why not?)

For her part, Tanaka appeared to casually observe two of the most important tenets of longterm health: curiosity and community. She kept her brain curious and agile, solving mathematics problems as a hobby; and she played an integral role in the world around her, engaging every day with family, customers and other members of her faith. (Tanaka was a devout Christian. Whatever your views on faith, engagement in religious communities has long been linked to longevity in Blue Zones throughout the planet.)

She reportedly made sure to eat and sleep well, too, which are essential to longterm health, but not in a manner that so many in the Western world have adopted, treating personal nutrition as some sort of punitive contest. Tanaka allowed herself treats, and retained her mirth. Years ago, she posed for her birthday photo while holding up a bottle of her beloved Coca-Cola.

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Kyle Kasperbauer on Calling it a Career: Retirement here we come - Morning Chalk Up

Photo Credit: Kyle Kasperbauer

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Kyle Kasperbauer still remembers his first workout. It was 2009 and Joe Westerlin, the co-owner of CrossFit Omaha along with Ricky Frausto talked him into coming into a class. Kasperbauer said hed already been working out consistently for three years after his college football career with some free weights, focusing primarily on strength training and accessory movements.

Then he was introduced to Helen, which is a three rounds for time workout with a 400 meter run, 21 kettlebell swings and 12 pull-ups.

It was eye opening, pride crushing, and almost humiliating. I loved it, said Kasperpauer. I had gotten beat by the majority of the class, which in my eyes at that time should not have happened, but it did because they were more fit than I was. That was a big piece of humble pie, and I embraced that. Anything that exposed my lack of fitness that effectively was the real deal. I jumped all the way in immediately.

Kasperbauers long history with the CrossFit Games also started in 2009 when he came in 37th. The 39-year-old, who has officially announced his retirement from the sport, got on the podium in 2012, and has now taken stock on a career that saw him go to the Games 10 times in total as both an individual, team and masters athlete.

CrossFit has changed drastically over the years for me as an individual, he said, looking back on his 14 years in the sport. It started as a way to compete and fulfill my desire for competition. Competing has been life for me since I was five years old, and CrossFit allowed me to continue competing. So I dug into the process and got to work. However, aside from competing, I do still respect my body and have a desire to maintain health and fitness as I age.

He said one of the most important things hes learned over the years is how to prime his body, and recover, which includes everything from warmup and coaching to hydration, nutrition and sleep. But no coffee, as Kasperbauer said hes never indulged to help his training.

CrossFit was actually a great resource for physical and mental longevity. Not only a physical workout, but a very effective mental stress reliever. It gave me the drive to get better. It gave me things to think about as I am performing the movement. Technique, technique, technique. Overall, in my opinion, CrossFit hasnt changed, but it has changed my life.

Kasperbauer holds a bachelors degree in Exercise Science and a Masters in Athletic Training Sports Medicine. He is the founder and co-owner of CrossFit Kinesis/Kinesis Fitness with Nissa Cohen, and the co-owner of Integrative Psychiatry with Macy Kasperbauer. He was born and raised in Nebraska, where he still lives to this day and runs his businesses.

Kasperbauers career has spanned almost everything CrossFit has seen. Rich Froning and Mat Frasers dynasty runs, a leadership change, and what many people are hoping is a new route for the sport and company coming out of the pandemic.

But he said at the core, CrossFit, in essence, never really changed at all.

The methodology hasnt changed. The movements are still the same. The definition is clear and concise. However, I have changed. My season in life has changed. So CrossFit within my life cycle has changed. People may have changed. Gyms may have evolved. Different people may be working for HQ. But at its core, CrossFit is what each gym and individual make it, and how much they want from it. The more you put into CrossFit, the more you will get back from CrossFit.

Kasperbauer said after a long and fortuitous career, he is more than ready for retirement, and calling it a career on competing in CrossFit.

Retirement here we come. After much thought, many prayers and multiple conversations with Macy, its time for a change. This would have been my 14th year in the sport. Time for the next chapter in my life. More time to focus on my faith, family, business and life, .in that order.

For a daily digest of all things CrossFit. Community, Competitions, Athletes, Tips, Recipes, Deals and more.

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Kyle Kasperbauer on Calling it a Career: Retirement here we come - Morning Chalk Up

Human wellbeing is increasingly viewed as a multidimensional phenomenon, of which income is only one facet (Stiglitz et al. 2009, OECD 2011, Proto and Rustichini 2014). However, economists continue to rely on GDP to gauge wellbeing (Oulton 2012). A way to assess GDP as a comprehensive measure of wellbeing is by looking beyond per capita income. In a recent paper, I focus on life expectancy at birth a synthetic measure of health and its relationship with per capita income over the past 150 years (Prados de la Escosura 2022).

An important caveat is that, when assessing life expectancy over time and across countries, we need to bear in mind that original values of life expectancy are bounded and that life quality improves with the quantity of years lived (Prados de la Escosura 2021). A solution is provided by Kakwanis (1993) non-linear transformation in which an increase in life expectancy at birth at a higher level implies a greater achievement than would have been the case had it occurred at a lower level.

Life expectancy (expressed as a Kakwani index) exhibits slightly faster long-run growth than per capita GDP. A closer look, however, reveals an apparent development puzzle: economic growth and life expectancy gains do not match each other (Table 1). During the globalisation backlash between 1914 and 1950, real per capita GDP growth slowed down as world commodity and factor markets disintegrated, while life expectancy experienced major gains across the board. But, from 1950 onwards, life expectancy achieved, on average, smaller gains to GDP per head. Thus, world average life expectancy exhibited a major advance across the board before 1950, earlier than usually presumed and at odds with the view that that global health only improved after WWII, when new drugs from the West reached the rest of the world (Acemoglu and Johnson 2007, Klasing and Milionis 2020).

Table 1 Trends in life expectancy and real per capita GDP

Notes: Kakwani Index (growth rates %)Sources: Foundation Rafael del Pino

Moreover, the evolution of life expectancy and per capita incomes international distribution is at odds. Life expectancy inequality rose from 1870 to the mid-1920s, fell until the early 1980s, and experienced a partial rebound over 19902010. In the case of per capita income, inequality rose up to the mid-1970s, stabilised, and then declined sharply since 1990.

Figure 1 International inequality in life expectancy and real per capita income, 1870-2015

Notes: Kakwani Index, population-weighted mean log deviation (MLD)

The annual cumulative growth rate by percentiles, from bottom to top (the growth incidence curve) also shows differences. In the case of life expectancy, the middle of the distribution experienced the main relative gains in the long run, followed by the lower-middle ventiles, and the smallest gains accrued to those at the top (Figure 2). As for per capita income, the bottom ventile achieved the lowest relative gains while the middle and the top of the distribution experienced the main relative gains

Figure 2 Growth incidence curves for life expectancy and real per capita income, 1870-2015 (%)

Source: Kakwani Index. See the text for further details.

What explains the different pace and breadth of life expectancy gains? It is commonly assumed that economic progress largely does. By raising average incomes, modern economic growth facilitates better nutrition, which strengthens the immune system and reduces morbidity (McKeown 1976, Fogel 2004). The increase in the public provision of health is another effect of higher average incomes (Loudon 2000, Cutler and Miller 2005). However, health improved across the board during the past 100 years, including in countries in which social spending did not expand and during phases of sluggish economic growth (Riley 2001, Sunde and Cervellati 2012).

Samuel Preston (1975) investigated the connections between life expectancy at birth and per capita GDP and concluded that increases in per capita income only explained a minor proportion of the rise in the lifespan, which was mainly attributable to the diffusion of medical advances resulting from the empirical validation of the germ theory of disease.

I tested Prestons association for a sample of 112 countries over 1870-2015, but instead of the original values, I used the Kakwani index of life expectancy and the natural logarithm of real per capita GDP at different cross-sections. The resulting relationship is convex, rather than concave as Preston observed. This suggests that advances in medical knowledge led to more-than-proportional gains in health as income rose. Moreover, the exercise confirms the existence of sustained outward shifts in the relationship over time, as put forward by Preston. Figure 3 shows a clear outward shift over time, but it does not proceed at the same pace between each pair of cross-sections. Thus, intense outward shifts between 1913 and 1950 and between 1970 and 2015 contrast with mild ones during 1870-1913 and 1950-1970.

Figure 3 Revisited Preston curve, 1870-2015

Over the past one and a half centuries, economic growth and medical advances appear to have contributed alike to longevity gains, but their contributions vary over time. Modern economic growth accounted for over 60% of the increase in the Kakwani index of life expectancy over 1870-1913 and, again, during the last period, 1970-2015. However, during the first half of the 20th century, three-fourths of the Kakwani index gains accrued to advances in medical knowledge. This finding matches Prestons lower bound estimates. Conversely, during the Golden Age (1950-1970) the increase in per capita income accounted for the entire improvement in the Kakwani index of life expectancy.

Life expectancy improvements can be depicted in terms of a health function (Easterlin 1999). Movements along the function represent gains attributable to economic growth and outward shifts of the health function result from improvements in medical knowledge. The strong outward shift in the health function during the first half of the 20th century arose from the diffusion of epidemiological transition. Triggered by the germ theory of disease, the epidemiological transition initiated in western Europe in the late 19th century and only started spreading worldwide from the 1920s (Riley 2001). Persistent gains in lower mortality and higher survival rates were achieved as infectious disease gave way to chronic disease as a major cause of death (Omran 1971). Two main consequences resulted from the diffusion of the germ theory of disease. On the one hand, medical technological progress resulted in new drugs to cure infectious diseases and spread the health transition (Easterlin 1999, Jayachandran et al. 2010, Lindgren 2016). On the other hand, and most decisively, low-cost improvements in public health derived from the diffusion of preventive methods of disease transmission and knowledge dissemination often through school education. This second channel of diffusion helps explain why the epidemiological transition spread in developing countries since the early 20th century, despite the fact that many of them were still under colonial rule and the new drugs were largely unaffordable.

Another significant outward shift of the health function took place in the late 20th century. This was the outcome of what may be depicted as a second health transition in which mortality and morbidity fall among the elderly as a result of new medical knowledge that allows better treatment of respiratory and cardiovascular disease (Cutler et al. 2006, Chernew et al. 2016, Eggleston and Fuchs 2012).

The substantial increases in longevity during the epidemiological transition were unevenly distributed throughout the world. Lack of economic means and basic scientific knowledge prevented a fast and wide diffusion of new medical technology and health practice across countries. In the late 19th and early 20th centuries, the increase in life expectancy inequality was due to the fact that the first health transition was initially restricted to advanced western countries. The gradual international diffusion of the health transition favoured the reduction in life expectancy inequality between the late 1920s and 1980. By 1970 the diffusion of the epidemiological transition was largely exhausted. The second health transition has been restricted so far to advanced countries due to its higher cost and this helps explain why inequality rebounded at the turn of the century.

Unlike the conventional wisdom, life expectancy at birth and real per capita GDP behaved differently in terms of trends and distribution during the past 150 years. Long-run improvements in life expectancy depended on advances of medical knowledge as much as on economic growth that facilitated better nutrition and the provision of health services. Thus, focusing only on movements along the health function, which derive from increases in average incomes, ignores the important shifts in the function that are closely connected to the diffusion of new medical knowledge.

Acemoglu, D and S Johnson (2007), Disease and Development: The Effects of Life Expectancy on Economic Growth, Journal of Political Economy 115: 925-985.

Chernew, M, D M Cutler, K Gosh and M B Landrum (2016), Understanding the Improvement in Disability Free Life Expectancy in the U.S. Elderly Population, NBER Working Paper 22306.

Cutler, D and G Miller (2005), The role of public health improvements in health advance: The twentieth century United States, Demography 42(1): 1-22.

Cutler, D M, A Deaton and A Lleras-Muney (2006), The Determinants of Mortality, Journal of Economic Perspectives 20: 97-120.

Easterlin, R (1999), How Beneficient is the Market? A Look at the Modern History of Mortality, European Review of Economic History 3(3): 257-294.

Eggleston, K N and V Fuchs (2012), The New Demographic Transition: Most Gains in Life Expectancy Now Realized Late in Life, Journal of Economic Perspectives 26: 137-156.

Fogel, R W (2004), The Escape from Hunger and Premature Death, 17002010. Europe, American and the Third World, New York: Cambridge University Press.

Jayachandran, S, A Lleras-Muney and K V Smith (2010), Modern Medicine and the Twentieth Century Decline in Mortality: Evidence on the Impact of Sulfa Drugs, American Economic Journal: Applied Economics 2: 118-146.

Kakwani, N (1993), Performance in Living Standards. An International Comparison, Journal of Development Economics 41: 307-336.

Klasing, M J and P Milionis (2020), The International Epidemiological Transition and the Education Gender Gap, Journal of Economic Growth 25: 3786.

Lindgren, B (2016), The Rise in Life Expectancy, Health Trends among the Elderly, and the Demand for Care. A Selected Literature Review, NBER Working Paper 22521.

Loudon, I (2000), Maternal Mortality in the Past and its Relevance to Developing Countries Today, American Journal of Clinical Nutrition 72(1) (supplement): 241S-246S.

McKeown, T (1976), The Modern Rise of Population, New York: Academic Press.

OECD (2011), Hows Life. Measuring Wellbeing, Paris: OECD Publishing.

Omran, A R (1971), The Epidemiological Transition: A Theory of Epidemiology of Population Change, Milbank Memorial Fund Quarterly 49(4): 509-538.

Oulton, N (2012), Hooray for GDP! GDP as a measure of wellbeing, VoxEU.org, 22 December.

Prados de la Escosura, L (2021), Augmented Human Development in the Age of Globalisation, Economic History Review 74(4): 946-975.

Prados de la Escosura, L (2022), Health, Income, and the Preston Curve: A Long View, CEPR Discussion Paper 17151.

Preston, S H (1975), The Changing Relationship between Mortality and the Level of Economic Development, Population Studies 29(2): 231-248.

Proto, E and A Rustichini (2014), GDP and life satisfaction: New evidence, VoxEU.org, 11 January.

Riley, J C (2001), Rising Life Expectancy. A Global History, New York: Cambridge University Press.

Stiglitz, J E, A Sen, and J P Fitoussi (2009), Report by the Commission on the Measurement of Economic Performance and Social Progress.

Sunde, U and M Cervellati (2012), Diseases and development: Does life expectancy increase income growth?, VoxEU.org, 6 January.

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Health, income, and the Preston curve | VOX, CEPR Policy Portal - voxeu.org

Immortality is the gift we might secretly desire but know would be an abominable curse to receive. To truly live forever would mean watching our loved ones die, generations at a time around us, and looking on while the natural world we value withers and falls into decay.

But while eternal life may be a fantasy, the prospect of us living longer lives than our predecessors is very real. The global Covid-19 pandemic might have interrupted proceedings, but the evidence clearly shows that over the long term the longevity of the worlds populations is unstoppably on the rise.

Even over relatively recent periods, the statistics are striking. In 1960, for example, the average life expectancy for men was 50.7 years, according to data from the World Bank, and for women it was 54.6.

Fast forward six decades to 2019, and World Bank figures show that the average life expectancy for men had grown to 70.6 years, and for women had edged past 75 years.

Looking into the future, the Hamburg, Germany-based market and consumer data firm Statista projects that, by 2050, the average life expectancy globally will reach 76.7 years and, by 2100, an impressive 81.7 years.

Given that these figures are averaged out across societies worldwide with wildly differing economic fortunes, that must surely mean that some people will be living considerably longer still.

Therein, of course, lies part of the explanation. The worlds populations are becoming wealthier, bringing with it improvements in diet and lifestyle and more advanced medical treatments and healthcare provision.

It seems hardly surprising that, according to World Bank figures, the 2019 average life expectancy of someone on a low income was 66 years, while for an upper-middle-income earner, it was a full 13 years longer, at 79.

The pace of developments in technology and in the provision of infrastructure such as roads, rail, schools and hospitals also means that as the worlds populations grow they are also urbanising more quickly. In short, our lives are better, from the moment we are born often in sanitised maternity units at the hands of trained experts to the moment we die, perhaps in a quality long-term care home.

Part of the deal, unfortunately, is that as we age, we tend to become more infirm and more vulnerable to diseases including conditions such as cancer, diabetes and heart disease.

Health and longevity make up one of the six themes that we have identified within the social and demographic change megatrend. And the more than 1,340 companies captured by the Fix the Future database strongly reflect some of the factors that are fuelling our longer lifespans.

By business line, they range from diagnostics and research firms to drug manufacturers, medical device makers, healthcare information providers and pharmaceuticals retailers.

The history of drug research and discovery is littered with casualties in the form of companies that believed theyd found a blockbuster treatment only to crash and burn in late-stage trials or founder when their medicine reached the market.

But there are plenty of established players, many of which have the backing of the worlds most skilled fund managers and are included in the Fix the Future database.

Among them is Novo Nordisk, a Denmark-based multinational that researches, develops and produces treatments for people with serious chronic diseases, including diabetes, obesity and rare blood and endocrine problems. (The endocrine system essentially regulates all of the bodys biological processes, including metabolism and blood sugar.)

Novo Nordisk is listed on the Nasdaq Copenhagen stock exchange with a market value of DKK 1.2tn (138bn). It produces half of the worlds supply of insulin for people with diabetes and says its aim is to prevent more than 100 million people from getting type 2 diabetes (often diet-related) by 2045. The company also carries out clinical trials in more than 50 countries.

From an investment perspective, this means that not only does Novo Nordisk have established, recurring and resilient sales, but it is also locked into long-term developments in demographics and growing healthcare needs.

There are numerous other routes into health and longevity as an investment theme, however. There are the manufacturers of medical equipment, for example, including Smith & Nephew, the UK-listed group most well known for its hip and knee replacements.

Listed on the London Stock Exchange with a market value of 10.6bn, Smith & Nephew also makes products to help stabilise fractures and correct bone deformities and has sports medicine and ear, nose and throat divisions, along with a unit that specialises in advanced wound management.

Crucially, the group describes itself as a medical technology company, signposting that it has its eye on the need to keep pace with modern treatments. In practice, that has meant building up its capabilities in robotics and digital surgery, and increasing its investment in research and development from 4.7% of sales in 2017 to more than 6% in 2021. With sales of just over $5.2bn (4bn) last year, that equates to about $312m.

Hospital operators such as HCA Healthcare provide the bricks and mortar of healthcare. This is a US business listed on the New York Stock Exchange, valued at just under $79bn, and which runs private hospitals and other centres in 20 American states as well as in the UK.

All told, HCA Healthcare manages more than 2,000 facilities, including hospitals and surgeries, emergency rooms and urgent care centres, as well as diagnostic and imaging units and walk-in physician clinics.

For an investor, that means HCA Healthcare is exposed to the structural growth of the private provision of healthcare and the harsh reality that well need more medical treatment in our old age.

And, of course, there are the insurers and sellers of healthcare plans, whose policies help cover medical bills and, in turn, help to underwrite the growth of private provision. Just one example is Fairfax Financial, a Canada-based business that also operates in parts of Asia, Europe and the Americas and is the owner of Brit Insurance in the UK.

Fairfax Financial is listed on the Toronto Stock Exchange and has a market value of just under C$14.6bn.

The company sells life cover and health insurance, among other financial services, so in this regard is positively plugged into the dynamics of ageing populations and their medical needs. However, it is also in the business of expanding opportunistically in regions where insurance penetration is low, which adds to its potential interest and ability to increase revenues.

Fairfax Financial has a solid foothold in high-growth Asian markets such as Indonesia, Thailand and Vietnam, where the populations are growing rapidly, wealth is on the up, and the safety nets of a welfare state are all but non-existent.

Like the rest of us, no company is immortal, but some of the smartest investors are working on the assumption that these and other businesses will be with us for some time to come.

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