Daily Archives: July 27, 2021

Benjamin Franklin had already turned 70 by the time he signed the US Declaration of Independence in 1776, when the average man wasn't expected to live to see 34. The inventor and statesman's remarkable longevity he died at the age of 84 has been attributed to avoiding alcohol and avidly swimming.

Global life expectancy at birth has now topped 70 years for men, and 75 years for women. And the population living to 100 and older is predicted to grow to nearly 3.7 million by 2050, from just 95,000 in 1990. According to a study published earlier this year, the biological hard limit on our longevity barring disease and disaster is as high as 150 years.

The progress made on extending lifespans thanks to vaccines and other breakthroughs has created complications, like difficulty funding retirement for growing elderly populations in some places. But its also inspired people to imagine a future where they pursue multiple careers and effectively combine several lives into one.

At certain points our prospects for longer lives havent looked great; US life expectancy saw its biggest decline last year since at least World War II, as COVID-19 was added to ongoing problems like drug overdoses. France, too, suffered a drop in life expectancy in 2020.

But there are clear indications more of us are headed the way of Jeanne Calment, the French woman who may have reached the age of 122 before dying in 1997.

Questions have been raised about Calments true longevity, but researchers from France and Switzerland say she was the oldest human being. Regardless, her official biography has captured the fancy of those who like the idea of being able to sip Port wine and eat more than two pounds of chocolate per week well past the century mark.

Clearly, the attractiveness of a longer life hinges on its quality.

The researcher Aubrey de Grey argues that the cellular decay behind ageing will be defeated. He's popularized the term Methuselarity to describe the point after which people with access to the right therapies will no longer suffer from age-related health problems, and human longevity will reach escape velocity (de Grey said recently that chances are decent this will occur by 2036).

Ray Kurzweil, an inventor and futurist, has likened the human genome to outdated software, and described ageing as a solvable engineering problem. Eventually we could extend our longevity indefinitely, Kurzweil has said, and relatively soon it may be possible to start adding one additional year to our lifespan every year.

There are potential economic benefits if people become able to live longer while staying healthier. A study published earlier this month used data from the US to suggest that effectively slowing the typical ageing process could create $38 trillion in value in a year of added life expectancy.

However, its unclear how evenly the tools needed for living longer and healthier lives would be distributed. Disparities in terms of healthcare and longevity, even within relatively wealthy countries, have become stark.

The OECD, a group of economically advanced countries, has reported that in 25 of its member states people with the highest level of education can expect to live about six years longer than those with the lowest level of education at age 30, for example.

The potential for effective anti-ageing innovation to worsen inequality in the future has stirred debate some say the advantages the affluent already have in acquiring everything from youth-preserving serums to face cream provide a glimpse of the issues to come.

For more context, here are links to further reading from the World Economic Forum's Strategic Intelligence platform:

On the Strategic Intelligence platform, you can find feeds of expert analysis related to Ageing and Longevity, Global Health, and hundreds of additional topics. Youll need to register to view.

Image: World Economic Forum

Written by

John Letzing, Digital Editor, Strategic Intelligence, World Economic Forum

The views expressed in this article are those of the author alone and not the World Economic Forum.

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How long are people going to live in the future? - World Economic Forum

Dena Dubals interest in sex differences in aging started early. Growing up in rural India, she was surrounded by great-grandmothers, great-aunts and others who far outlived the men in the family. Her family wasnt unusual. Across the world, women typically outlive men by approximately five years and experience slower rates of age-related cognitive decline.

Now, as a neuroscientist at the University of California, San Francisco, Dubal is starting to uncover why those differences occur. In videos of aging mice wandering through a maze, she points out how some animals appear confused, meandering much like people trying to find their cars in a parking garage. Others take quicker, more focused routes through the maze, as if they remember exactly where they left their vehicle. Dubal recently discovered that the difference between these animals stems, in part, from a protein made by a gene on the X chromosome. Over the last several years, her research has homed in on sex chromosomes as a vital contributor to how our brains age.

Two X chromosomes lead to female hormones and features, while an X and Y lead to male traits. These differences affect glucose metabolism, cellular energy production and much more, according to Dubal, an investigator with the Simons Collaboration on Plasticity and the Aging Brain. Sex chromosomes and gonadal hormones alter fundamental biology in ways that we are just beginning to understand, she says. The X chromosome is 5 percent of our genome, and it has the largest density of brain-related genes compared to any individual autosome. I dont think its coincidence that variations or human mutations in these different X factors affect brain function.

Understanding these differences will be important for developing new treatments. In 2003, the National Institute on Aging (NIA) launched a program to help assess drugs or dietary interventions that could safely extend the life span of mice and eventually humans. This Intervention Testing Program supports studies of approximately 10 to 15 treatments each year, and researchers test interventions in both male and female animals. In 2015, researchers reviewed 14 interventions that had been tested over the previous decade. They found that only five appeared to actually extend life span and four of those worked differently in male and female animals. That suggests theres a fundamental difference in the way we age, said Brnice Benayoun, a biologist at the University of Southern California, in a 2020 podcast.

Dubal and Benayoun are now probing the mechanisms underlying these observations, examining how steroid hormones and sex chromosomes alter the trajectory of cognitive decline with age in different sexes.* Their studies, part of an SCPAB project on sex differences in aging, will help reveal why women are on average more resilient to cognitive decline, memory loss and other brain functions that erode as we grow old. Identifying these factors could inspire interventions that benefit everyone improving not just a persons life span but their quality of life as they age. The things that help us live longer also tend to be the things that help us live better, Dubal says.

Seeking clues as to why a 70-year-old woman is likely to appear far more youthful than a man of the same age, Steve Horvath, a geneticist at the University of California, Los Angeles, and his colleagues looked for changes in DNA methylation, also known as epigenetic markers, that control gene expression. They examined blood, brain, lung, liver and other tissues across the human life span and found many sex-associated differences. Samples from older adults showed signs of demethylation, particularly at enhancers and regulatory elements in the genome, which control when a particular gene produces protein and how much. Men typically appeared older and showed more signs of such loss compared to women of the same age. The contrast was most pronounced in liver and blood, and to a lesser extent in brain tissues.

Methylation hints at the cellular mechanisms underlying female cognitive resilience as well as their longer life spans, Horvath says. Its a very consistent finding that women age more slowly than men in several different organs, so on some level methylation reflects that mortality advantage, he says. It could easily be part of the explanation for cognitive resilience but I would never say it explains it all.

In 2019, another clue emerged from studies of how the brain consumes glucose. Manu Goyal, a neuroradiologist at Washington University in St. Louis, found that younger brains use a mix of two cellular pathways, oxidative and non-oxidative metabolism, to break glucose down and fuel their activity. Some older brains shift mostly to oxidative. When Goyal and his colleagues imaged glucose metabolism in the brains of 205 cognitively normal adults aged 20 to 82, they found that female brains on average appeared younger than those of age-matched males by approximately three years.

Surprisingly, mice with two X chromosomes whether they bore ovaries or testes lived longer than their XY littermates. Dubal and her colleagues were the first to note this effect of the X chromosome on life span in a 2018 study. The XX mice also performed better on tests of memory and spatial learning, such as finding their way to a platform through a water maze. If estrogen were the only factor responsible for longevity, then all mice with ovaries should show these advantages, Dubal says. But only XX mice did, whether they had ovaries or testes.

Typically, cells with two X chromosomes silence one set of X-linked genes by epigenetic mechanisms such as methylation, to avoid a double dose of X-linked proteins. In principle, a silenced X should be inactive. But at least 15 percent of X-linked genes in humans escape this silencing. Theres really a handful of factors that escape X inactivation in the brains of both humans and mice, Dubal says.

In a study published in August 2020, the team homed in on four such genes that are expressed in the brain and appear to slip past their epigenetic off-switches, resulting in increased levels of these proteins in XX cells. Some have been linked to intellectual disability and autism.

At a lab meeting, Dubal and her team took a vote on which of the four theyd pursue; the winner was a gene named lysine demethylase 6a, or KDM6A. Not much was known about it, she says. People with mutations in this gene have syndromes that involve intellectual disability and it seemed to be important to how brain cells connect at the synapse in mice. That was enough of a clue for us to wonder whether this was involved in cognitive aging and neurodegenerative diseases.

The KDM6A protein unspools DNA from histones, opening it up to be transcribed and controlling the expression of many other genes. In a series of experiments, Dubal and her team discovered that XX cells, which have higher levels of KDM6A, were more resistant to neurotoxins than XY cells. Decreasing KDM6A levels in XX cells made them more vulnerable to toxins, including -amyloid, a misfolded peptide linked to Alzheimers disease. Boosting levels of the KDM6A protein in XY cells made them more resilient to these exposures and improved XY animals spatial memory, enabling them to remember the location of a platform hidden within a maze and move swiftly toward it much like finding ones car in a garage.

Dubals team has also analyzed databases of genetic variants in Alzheimers disease and found an association between the presence of a genetic variant that increases levels of KDM6A in the brain and lower levels of cognitive decline. Such data could eventually lead to new interventions to prevent age-related loss in brain function and not just in women. If we can unravel what makes one sex more resilient or vulnerable than the other in a specific measure, Dubal says, that could mean novel therapies that could protect both sexes.

In a study published in Nature Aging in July, Benayoun and her colleagues studied how immune cells known as neutrophils changed with age in male and female mice. They found that an animals sex was a strong predictor of immune responses. Neutrophil activity followed sex-specific trajectories as animals aged: Cells from male mice showed higher levels of inflammatory proteins that can damage surrounding tissues, while those from female animals increased the production of extracellular structures correlated with autoimmune disease. These findings suggest that sex differences can become amplified with aging, at least for neutrophils, Benayoun said in a press release.

Benayoun is now developing a mouse model to understand how testosterone and estrogen regulate these processes. Their model allows researchers to externally reverse an adult animals gonads. They can reprogram an ovary-bearing mouse, born with two X chromosomes, to convert the ovaries into testes and produce levels of testosterone that are nearly identical to those of their XY-chromosome-bearing littermates. The model will allow them to answer questions such as how a lifelong exposure to testosterone affects neuro-inflammation or microglia in two animals with identical genetic backgrounds. Its going to help us identify whats beneficial or not in terms of these hormones which are known to modify brain physiology, she says.

To understand how sex hormones shape brain function over a lifetime, Benayoun has turned to the African killifish, a brightly colored tropical fish thats the shortest-lived vertebrate scientists can breed in labs. Killifish life spans range from 3 to 6 months, because they evolved in seasonal ponds of rainwater that dry up for half a year. Their live fast, die young lifestyle makes them ideal subjects for studying aging. They age five to six times faster than a mouse and almost 10 times as fast as zebra fish, Benayoun says. Its so powerful because we can recapitulate most of what we expect from human aging, including cognitive decline, in that short amount of time.

Her team studies two strains of the fish one that evolved in regions with a longer dry season, and another from a region with longer monsoons that allow the strain to live 30 to 40 percent longer than the other. Killifish sex is determined by X and Y chromosomes, so Benayoun aims to use single-cell RNA sequencing and other analyses to seek out sex differences in males and females in both the long-lived and short-lived strains. Theres not a lot of work in the species yet, she says. But we have every reason to believe they will have sex differences like any other vertebrate species.

*Note: Their projects and this story focus on the biological classification of worms, mice and humans as male and female. They do not capture gender, a persons innate sense of identity as male, female, a combination, or a different gender.

Reference:Lu RJ, Taylor S, Contrepois K, et al. Multi-omic profiling of primary mouse neutrophils predicts a pattern of sex- and age-related functional regulation. Nat Aging. 2021:1-19. doi:10.1038/s43587-021-00086-8

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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The XX Factor: What's the Key to Female Longevity? - Technology Networks

Pollution is causing human penises to shrink, according to one scientist.

A leading epidemiologist and environmental expert has published a book that examines the link between industrial chemicals and penile length.

Dr Shanna Swan's book, Count Down, argues that our modern world is altering humans' reproductive development and threatening the future of our species.

The book outlines how pollution is leading to higher rates of erectile dysfunction, fertility decline, and growing numbers of babies born with small penises. Though the headline fact about shrinkage may sound like a laughing matter, the research paints a bleak portrait of humanity's longevity and ability to survive.

"In some parts of the world, the average twenty-something today is less fertile than her grandmother was at 35," Dr Swan writes, dubbing the situation a "global existential crisis" in the book.

Chemicals in our environment and unhealthy lifestyle practices in our modern world are disrupting our hormonal balance, causing various degrees of reproductive havoc."

According to the book, humans meet three of the five possible criteria used to define whether or not a species is endangered. "Only one needs to be met," writes Dr Swan, "the current state of affairs for humans meets at least three."

According to Dr Swan's research, this disruption is caused by phthalates, chemicals used in plastic manufacturing, which can impact how the hormone endocrine is produced.

This group of chemicals is used to help increase the flexibility of a substance. They can be found in toys, food packaging, detergents, cosmetics, and many more products. But Dr Swan believes that these substances are radically harming human development.

"Babies are now entering the world already contaminated with chemicals because of the substances they absorb in the womb," she says. Much of Dr Swan's recent work has focused on the effects of phthalates, initially looking at phthalate syndrome in rats.

In 2000, however, there was a breakthrough in the field, and it became possible to measure low doses of phthalates in humans.

Since then Dr Swan has authored papers on how these chemicals can pass between parents and their offspring, the impact on female sexual desire, and - most recently - on penile length.

One of her most famous studies examined the intersection between sperm count and pollution in 2017, in ground-breaking research which looked at men's fertility over the last four decades. After studying 185 studies involving almost 45,000 healthy men, Dr Swan and her team concluded that sperm counts among men in Western countries had dropped by 59 per cent between 1973 and 2011.

But there is some good news. Since the creation of the European Environment Agency, European citizens are exposed to 41 per cent less particulate pollution than we were two decades ago. It's believed that these regulations have gifted Europeans an extra nine months of life expectancy, on average.

A demand for change from citizens and subsequent strong policies have helped to clear the air in parts of Europe before, and can continue to do so to ensure that high pollution today does not need to be tomorrows fate," says Michael Greenstone, director of the Energy Politics Institute at the University of Chicago.

So if pollution reduction measures can be properly implemented, there is still hope for the future and humanity's fertility.

Read more here:
Environmental scientist warns that pollution is causing penises to shrink - Euronews

At age 96, Patricia Segal lives alone in an airy Sydney apartment with views of the sea. Time spent with her feels uplifting, invigorating, and when you ask for her secret Segal doesnt hesitate: her positive and curious attitude is the key to her longevity, she says.

And although scientists don't understand exactly why, research suggests she is correct.

As COVID-19 continues to expose the vulnerability of Australias elderly and an inquiry laid bare abuse in aged care homes Segal projects a dramatically different image of what it can mean to reach very old age.

She does not appear as a woman eyeballing 100. Segal looks years younger. Stylishly and carefully dressed, with her hair kept dark brown and cropped close, she radiates calm, upbeat confidence.

ABC News: Catherine Taylor

Our conversation roves across politics and sociology. The novel shes currently reading rests on her coffee table shes regular a member of two local libraries. Her apartment is decorated with original artwork the fruits of a painting hobby that she first took up aged 90-something.

"I just thought Id try it. I walked into the art class one day, everybody said 'hi!, everybody was smiling. The teacher was fantastic and it's just wonderful," she explains. "Sometimes when I look at the paintings I think 'did I really do that?'"

Researchers say Australians are entering an era in which remaining vital well into your 90s will be not just possible, but common. And your 80s may well deliver some of the best years of your life.

The average lifespan of an Australian woman is now about 85, packing on 25 additional years in a century, meaning one in two women will reach this age or beyond.

That's an ageDexter Kruger, Australia's oldest personbefore hepassed away this weekaged 111, reached with ease. Research suggests he's not alone:Centenarians are now Australia's fastest-growing demographic.

ABC News: Phoebe Hosier

Between 2000 and 2020 the numbers of Australians aged over 85 grew by 110 per cent, compared with national population growth of 35 per cent. A baby girl born today has an almost 40 per cent chance of reaching 100.

Life expectancy for men is increasing along a similar upwards curve, just behind the long-lived women.

Professor Perminder Sachdev, a neuropsychiatrist at the University of NSW, is leading the Sydney Centenarian Studythat is hunting for environmental and genetic determinants of successful ageing.He wants to know how the brain ages, and has enrolled around 450 study participants ranging in age from 95 into theirearly 100s.

Although the lifespan of Australians is increasing Sachdev says up to 50 per cent of people will suffer some kind of cognitive decline including dementia or Alzheimer's disease once they near 100.

It is a reality that concerns Segal, who says she does not want to reach a century if she is no longer in control. "Old people can get pretty useless," she says. "I've got a wonderful family but I don't want them to have to worry about me. I'm very, very lucky. I've had a wonderful life. I haven't missed anything."

ABC News: Catherine Taylor

Solving the riddle of what it takes to not just live longer, but do it with verve and enthusiasm and without mental impairment, is what Sachdev's team hopes to unravel.

There's no one pathway to a healthy long life, Sachdev says. It is a puzzle that is still being completed.

Increasing lifespans have paralleled improvements in healthcare, nutrition and education, as well as rising quality of life for most Australians that helps to ensure things like stable housing, another longevity indicator. Lifestyle improvements have also been significant particularly a successful campaign to reduce smoking. Even playing tennis has been pinged in one studyfor its associationwith greater longevity than other sports.

"All we have [to work with]are lifestyle factors," Sachdev says, and "we realise that these factors impact from birth. Ideally one wants a lifetime of good effort."

But researchers like Sachdev, and Professor Henry Brodaty who collaborates with him on the centenarian study, note growing evidence that successful ageing includes less tangible and more mysterious influences.

Segal's comment about her attitude to life was spot on. An optimistic personality, strong social connections and what the Japanese call "ikigai", a reason for being, are all core attributes of long lifers.

"We found people who are 100-plus and they are still volunteering in committees and other areas, engaged socially and with their great grandchildren, Sachdev says. It is this kind of physical and mental activity we tend to see repeated in different [ageing] studies around the world."

Quality education in childhood, and lifelong learning, is also key. Precisely how it impacts longevity and brain health is not fully understood.

Sachdev hypothesises that education may raise the likelihood of making sensible lifestyle choices, or offer socioeconomic benefits, like access to higher-paying job that puts a better standard of housing andhealthcare within reach andin turn predisposes these people to healthier bodies in old age.

He also argues that there are indications education builds "better cognitive reserves during the developmental period and you set yourself up for a lifetime of more complex cognitive activity".

"All the data points to the fact that if there is one thing we should do (to maximise healthy aging)it is improve the quality of education," he says. "Because people who had better education preserved their brains."

The lifestyle ingredients of longevity are so routinely effective as to feel almost predictive of long life. Could there be a "recipe"for successful ageing?

Regions around the world known as "blue zones" where the populations have unusually high numbers of centenarians offer clues.

The islands of Sardinia in Italy, Ikaria in Greece and Okinawa in Japan as well as Costa Rica's Nicoya Peninsula and California's community of Seventh Day Adventists in Loma Linda make up five zones where residents outlive the rest of the world.

Researchers have also distilled nine traits of these communities that are credited with underpinning each community's health.

They include:

Blue zones are less pronounced in Australia and pockets of longer-lived citizens tend to be linked to socioeconomic advantage. The ACT and Sydney's affluentsuburbs of Mosman, Hunters Hill as well as the Hills District,emerge as areas where residents have a slightly higher than average life expectancy.

In the Northern Territory, however, life expectancy is concerningly below the national average. Yet NT has also shown the greatest percentage growth in over 85s in Australia, suggesting disadvantage is slowing.

Longevity zones in Australia are also linked to retirement communities, Henry Brodaty notes, where higher concentrations of older people in turn creates a greater probability of encountering the 95-plus cohort. This is a quirk of internal migration rather than a true, blue zone.

In Segals case, as we talk, it's astounding how consistently her natural choices throughout life offer a real-world masterclass in hitting those longevity KPIs: never a smoker, a light and occasional drinker, Segal remains close to her two children, four grandchildren and 10 great grandchildren.

She's been active throughout life, a regular at the tennis club, and now walks everywhere ("I'm considering getting a walking stick not for stability but because it allows me walk even faster"). And she eats small, healthy meals that she cooks herself ("I've never cared about food").

And what about her self-acknowledged positive attitude to life?

One of the difficulties of living into very old age is that lifelong friends pass away, become ill or do not maintain the same attitude to living, Segal says. Her husband died four years ago at age 95, and Segal is matter-of-fact as she explains that loneliness can be one of the hazards of a long life.

Unwilling to slow down and give up her social nature, Segal enlisted her granddaughters to match her up with the grandmothers of their friends so she could expand and rebuild her friendship group as she aged.

"I've been lucky, I've made new friends," she says with trademark pragmatism. "I like to go out at least twice a week. I probably go out more than that but as long as I'm out twice a week I'm quite happy on other days to stay home and just read or write."

Even COVID lockdown hasn't slowed her down. Segal continues to swap books and the library and keep in touch with friends and family.

Segal also acknowledges how fate has worked in her favour. She fled Berlin with her Jewish family just before World War II, escaping the horrors that were to unfold in Europe. She grew up in a loving home and had a very happy marriage without financial pressure.

It's impossible to talk about longevity without considering the genetic lottery. Our DNA can protect or betray us no matter what healthy lifestyle choices we make.

Sachdev points out that genetics is an important part of the long-life puzzle, particularly for those who reach extreme old age, 100-plus, in great health. Hitting a century is where genes start to have real impact, and the limits of medical science begin to be felt, he says.

"The genetic factors are polygenic," says Sachdev, meaning that many genes are involved in predisposing someone to a long lifespan. Just how to manipulate these genes to deliver the same genetic advantage to everyone has not been solved.

"You notice that many people who reach 100 or above have been able to avoid illness altogether," he says.

"They have not developed the chronic illnesses that affect most of us, things like hypertension, diabetes or arthritis. Alternatively, if they do develop these problems, then they develop them at a later age, say their 80s or 90s rather than the 60s and 70s."

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When you look at global blue zones on a map two fascinating facts emerge: many are islands, and all lie in regions where the weather is warm and sunny for a good part of the year.

The warm weather may well encourage people to leave their homes and congregate in groups, building the social connections and optimism that are traits of those who age well.

These blue zone communities are also somewhat cut off from the outside islands, or peninsulas or closed religious communities: it is possible that generations of good genes were distilled within these groups and go some way to explaining why residents have such long lives.

In Segal's case it's debatable how much her genetics has influenced how well she has aged. Her father died at 72 and although her mother lived to 92, she was unwell from her late 80s but this would still have been beyond the life expectancy for women at that time.

Jim Hennington's job is to take one of life's biggest mysteries how long we might live and spin it into the kind of mathematical data that is so reliable hes willing to bet literally millions of dollars on it as part of his work in superannuation.

Hennington, a fellow of the Institute of Actuaries of Australia, says the data on human lifespan is remarkably predictable.

He points to a steady increase in average lifespan over decades and the smooth, comforting curves they produce when graphed mathematically. While the length of an individual life will always be unknown, he says, across a population the patterns are undeniable.

Those patterns hide even more interesting statistics, Herrington says, that influencing superannuation policy.

While the average life expectancy of an Australian woman is now 85, in reality, if an Aussie woman hits 65 in good health and with quality housing and lifestyle, she has as much chance of reaching 100 as dying before 86, Herrington says.

Reuters: Jean-Paul Pelissier

The remarkable lives of people like French woman Jeanne Calment, who lived to 122 and was assessed as cognitively sharp at age 121,raise hopes that years of healthy, active life can be further extended.

Sachdev believes that evidence humans can routinely survive to 110, 120 or even 150, is "not really that strong".

But surviving into your 90s, and staying mentally sharp and physically active, and more and more of us hitting the big 1-0-0, is a very real possibility, he says.

And as Patricia Segal knows, that's something to feel optimistic about.

See more here:
Australians are living longer but what does it take to reach 100 years old? - ABC News