Daily Archives: February 5, 2022

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Rfrences

[1] Alexey A. Moskalev et al., The Role of DNA Damage and Repair in Aging through the Prism of Koch-like Criteria, Ageing Research Reviews 12, no. 2 (March 2013): 66184, doi:10.1016/j.arr.2012.02.001.

[2] Pter Bai and Carles Cant, The Role of PARP-1 and PARP-2 Enzymes in Metabolic Regulation and Disease, Cell Metabolism 16, no. 3 (September 5, 2012): 29095, doi:10.1016/j.cmet.2012.06.016.

[2] Nady Braidy et al., Age Related Changes in NAD+ Metabolism Oxidative Stress and Sirt1 Activity in Wistar Rats, PLOS ONE 6, no. 4 (avr 2011): e19194, doi:10.1371/journal.pone.0019194.

[3] Weihai Ying et al., NAD+ as a Metabolic Link between DNA Damage and Cell Death, Journal of Neuroscience Research 79, no. 12 (January 1, 2005): 21623, doi:10.1002/jnr.20289.

[4] Judith Campisi, Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors, Cell 120, no. 4 (February 25, 2005): 51322, doi:10.1016/j.cell.2005.02.003.

[5] Braidy et al., Age Related Changes in NAD+ Metabolism Oxidative Stress and Sirt1 Activity in Wistar Rats.

[6] Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak, Telomeres and Telomerase: The Path from Maize, Tetrahymena and Yeast to Human Cancer and Aging, Nature Medicine 12, no. 10 (October 2006): 113338, doi:10.1038/nm1006-1133.

[7] Jerry W. Shay and Woodring E. Wright, Senescence and Immortalization: Role of Telomeres and Telomerase, Carcinogenesis 26, no. 5 (May 1, 2005): 86774, doi:10.1093/carcin/bgh296.

[8] Mary Armanios and Elizabeth H. Blackburn, The Telomere Syndromes, Nature Reviews. Genetics 13, no. 10 (October 2012): 693704, doi:10.1038/nrg3246.

[9] Partial Reversal of Aging Achieved in Mice, Harvard Gazette, accessed September 2, 2016, http://news.harvard.edu/gazette/story/2010/11/partial-reversal-of-aging-achieved-in-mice/.

[9] S. Sayols-Baixeras et al., Identification and Validation of Seven New Loci Showing Differential DNA Methylation Related to Serum Lipid Profile: An Epigenome-Wide Approach. The REGICOR Study, Human Molecular Genetics, September 15, 2016, doi:10.1093/hmg/ddw285.

[10] Gianluca Pegoraro et al., Aging-Related Chromatin Defects via Loss of the NURD Complex, Nature Cell Biology 11, no. 10 (October 2009): 126167, doi:10.1038/ncb1971.

[11] Chunyu Jin et al., Histone Demethylase UTX-1 Regulates C. Elegans Life Span by Targeting the insulin/IGF-1 Signaling Pathway, Cell Metabolism 14, no. 2 (August 3, 2011): 16172, doi:10.1016/j.cmet.2011.07.001.

[12] Ibid.

[13] Susmita Kaushik and Ana Maria Cuervo, Proteostasis and Aging, Nature Medicine 21, no. 12 (December 2015): 140615, doi:10.1038/nm.4001.

[14] D. E. Feldman and J. Frydman, Protein Folding in Vivo: The Importance of Molecular Chaperones, Current Opinion in Structural Biology 10, no. 1 (February 2000): 2633.

[15] Stuart K. Calderwood, Ayesha Murshid, and Thomas Prince, The Shock of Aging: Molecular Chaperones and the Heat Shock Response in Longevity and Aging A Mini-Review, Gerontology 55, no. 5 (September 2009): 55058, doi:10.1159/000225957.

[16] Protein Modification and Maintenance Systems as Biomarkers of Ageing, n.d.

[17] Ryan Doonan et al., Against the Oxidative Damage Theory of Aging: Superoxide Dismutases Protect against Oxidative Stress but Have Little or No Effect on Life Span in Caenorhabditis Elegans, Genes & Development 22, no. 23 (December 1, 2008): 323641, doi:10.1101/gad.504808.

[18] Ana Mesquita et al., Caloric Restriction or Catalase Inactivation Extends Yeast Chronological Lifespan by Inducing H2O2 and Superoxide Dismutase Activity, Proceedings of the National Academy of Sciences of the United States of America 107, no. 34 (August 24, 2010): 1512328, doi:10.1073/pnas.1004432107.

[19] Michael T. Ryan and Nicholas J. Hoogenraad, Mitochondrial-Nuclear Communications, Annual Review of Biochemistry 76 (2007): 70122, doi:10.1146/annurev.biochem.76.052305.091720.

[20] Tamara Tchkonia et al., Cellular Senescence and the Senescent Secretory Phenotype: Therapeutic Opportunities, Journal of Clinical Investigation 123, no. 3 (March 1, 2013): 96672, doi:10.1172/JCI64098.

[21] Chunfang Wang et al., DNA Damage Response and Cellular Senescence in Tissues of Aging Mice, Aging Cell 8, no. 3 (June 2009): 31123, doi:10.1111/j.1474-9726.2009.00481.x.

[22] Isabel Beerman et al., Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging, Cell Stem Cell 12, no. 4 (April 4, 2013): 41325, doi:10.1016/j.stem.2013.01.017.

[23] Claudia E. Rbe et al., Accumulation of DNA Damage in Hematopoietic Stem and Progenitor Cells during Human Aging, PLoS ONE 6, no. 3 (March 7, 2011), doi:10.1371/journal.pone.0017487.

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Aging 101: Biological causes of aging - Work for human ...

Social isolation and loneliness were independently associated with a higher risk of incident cardiovascular disease (CVD) in a recent study of older women in the United States, suggesting the need for increased prevention in this cohort.

The study data show an 11.0% - 16.0% higher risk of CVD among postmenopausal women, while higher levels of social isolation and loneliness were associated with a 13.0% - 27.0% higher risk of CVD

Led by study authors Natalie M. Golaszewski, PhD and John Bellettiere, PhD, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, the study hypothesized fewer associations with risk of CVD would be found among women with greater social support.

The prospective cohort study was conducted from March 2011 - March 2019 and included women (65 - 69 years old) from the Womens Health Initiative Extension Study with no history of myocardial infarction, stroke, or coronary heart disease.

To obtain this population, investigators found two sets of data:

After exclusion of the latter group, 57,825 (94.5%) women were left for follow-up until the end of the study period of the first reported major CVD event.

Main outcomes were considered major CVD and the first reported occurrence of the event was physician adjudicated using medical records. Both social isolation and loneliness were evaluated utilizing validated questionnaires, including the UCLA Loneliness scale, while social support was assessed using 9 items from the 19-item Medical Outcomes Study Social Support Survey.

Additionally, hazard ratios (HRs) and 95% CIs for CVD were calculated for women with high social isolation and loneliness scores, compared lower scores using multivariable Cox proportional hazards regression models.

In the total cohort (n = 57,825), the mean age was 79.0 years and 89.1% identified as non-HIspanic White. A higher percentage of participants with above-median social isolation and loneliness had depression and diabetes and more likely report poorer self-rated health and less social support.

A total of 1599 major CVD events occurred over 186,762 person-years. Rates of CVD events among women with above-median loneliness was 11.5 per 1000 person-years and 7.4 per 1000 person-years among women with below-median loneliness.

Investigators observed the HR for the association of high versus low social isolation scores with incident CVD was 1.18 (95% CI, 1.13 - 1.23; 18.0% higher risk) and the HR for the association of high versus low loneliness scores with CVD was 1.14 (95% CI, 1.10 - 1.18).

Following additional adjustment for health behaviors and health status, the HR was 1.08 (95% CI, 1.03 - 1.12; 8.0% higher risk) for social isolation and 1.05 (95% CI, 1.01 - 1.09; 5.0% higher risk) for loneliness.

Then, the HRs for the association of both high social isolation scores and high loneliness scores versus both low social isolation scores and low loneliness scores were 1.27 (95% CI, 1.21 - 1.36; 27.0% higher risk) and 1.13 (95% CI, 1.06 - 1.20; 13.0% higher risk), after adjustment.

Lastly, social support was not found to be a significant effect modifier of the associations (social isolation x social support: r, -0.18; P = .86; loneliness x social support: r, 0.78; P = .48).

The mechanisms through which social isolation and loneliness are associated with incident CVD may partially involve health behaviors and changing health status, although in this study, the results suggest that the associations were not fully explained by these factors, investigators concluded.

The study, Evaluation of Social Isolation, Loneliness, and Cardiovascular Disease Among Older Women in the US, was published in JAMA Network Open.

Excerpt from:
Higher Risk of Incident CVD in Older Women Linked to Social Isolation, Loneliness - MD Magazine

Medical educators and the bodies that oversee medical schools have long been unenthused by publications that purport to rank the quality of medical schools. A recent shift in those rankings may be a step in the right direction, according to a Viewpoint column published in JAMA Health Forum, but theres still much work to be done.

Heres a look at why the contention that medical school rankings remain a beauty contest has some merit and why medical students advise pre-meds to look beyond the best-of lists to find the right fit.

Reputation still overweighted

The Viewpoint column, Increasing Transparency for Medical School Primary Care RankingsMoving From a Beauty Contest to a Talent Show, was written by Robert L.PhillipsJr,MD, MSPH,Andrew W.Bazemore,MD, MPH,and John M.Westfall,MD, MPH, who are affiliated with the American Board of Family Medicine (ABFM) and other organizations that promote primary care.

In the column, the authors noted how the well-known U.S. News & World Report rankings have evolved with regard to primary care.

The new overall Best Medical Schools for Primary Care rankings were modified in 2021 such that 30% of the score is now based on graduates practicing primary care after their residency training rather than those entering primary care training. Initial residency comprises 10% of the score, which still overestimates primary care, but this measure has been reduced from its previous weighting of 30%, the commentarys authors wrote. The remaining score (60%) is still largely based on reputation.

The reputation metric having such weight in the case study left schools that produce the most primary care physiciansbut may not have the name recognitionout of the rankings.

Learn more about why when it comes to the best medical schools, fit is more important than rankings.

Rankings are self-perpetuating

Nearly 80% of respondents to the 2020 matriculating medical student questionnaire, conducted by the Association of American Medical Colleges, stated that the general reputation of a medical school was an important or very important factor when selecting a medical school.

As highlighted in past critiques, the rankings themselves can be a flattering piece of marketing. A September 2019 commentary in the journal Academic Medicinecited in the JAMA Health Forum Viewpoint columncalled on several more important selection criteria that students should consider.

Quality education, community service, professional diversity, research excellence, health advocacy, interprofessional care, fostering of student resiliency and well-being, and other outcomes are better metrics of medical school quality than the currently flawed rankings, the authors wrote at the time.

The JAMA Health Forum commentarys lead author, Dr. Phillips, cautioned any use of rankings as a primary evaluation metric for selecting a medical school.

Students should be careful in using medical school rankings to inform their choices as many rankings are opinion-driven, said Dr. Phillips, who directs the Center for Professionalism and Value in Health Care at the American Board of Family Medicine Foundation.

He said the more data-driven U.S News rankings, developed with data from the Robert Graham Center, does offer pre-meds a better tool to consider as they decide where to apply or enroll.

We also hope that the new ranking heralds continued improvement of the information that help students make career decisions, Dr. Phillips said.

Importantly, the revised rankings add four new data-driven measures to account for student diversity, the proportion of graduates who practice in primary care, and those who practice in rural or medically underserved areas. What matters most, however, is going to be up the individual medical school applicant.

What really matters

Alec Calac is an AMA member and MD-PhD student at the University of California, San Diego School of Medicine and Herbert Wertheim School of Public Health and Human Longevity Science. As a pre-med, he felt that personal interactions were far more important.

Rankings really did not matter to me, Calac said. I wanted to train somewhere that valued not just what I had done, but who I was.

I knew that I would receive a great education wherever I went. But at the end of the day, it was not about rankings. It was about the interactions that I had with students, staff and faculty of color during revisit programs, added Calac, of the Pauma Band of Luiseo Indians.

Check out these four tips for choosing the right medical school.

More here:
Why pre-meds should think twice about medical school rankings - American Medical Association

Biohacking is, in a way, lifehackings bizarro-world twin. (Bio means life, after all.) Lifehacking isnt an organized movement or even really a word, never mind the name of the website youre reading right now; biohacking has cult status and people will identify themselves as followers of the practice. Lifehacking is just part of, you know, life; biohacking has its gurus and buzzwords.

But what is biohacking when you get down to it? The answer will depend on who you ask. There are grinders who implant devices under their skin; and then there are tech bros who will skip breakfast or take a cold shower and call it a biohack.

In the broadest sense, biohacking is any practice that changes the structure or function of the body. I once went to an anarchist-flavored biohacking conference where strength training and birth control were each brought up multiple times as examples of effective, well-accepted biohacks. (Much more out-there stuff was discussed, but these provided common ground everyone could agree on.)

When you look at it that way, almost anything can be a biohack. But that also means a lot of the trendier biohacks are simply new, unproven, potential solutions for problems that already have solutions.

Scrolling through biohacking forums or reading the blogs of prominent biohackers will reveal the problems theyre trying to solve are familiar ones. Biohackers want to get more sleep; reduce their risk of cardiovascular disease, cancer, and diabetes; focus better at work or while pursuing their hobbies; lose weight; and prevent or manage mental health issues like depression. Biohackers: Theyre just like us!

In the same sense that alternative medicine that works just becomes medicine, biohacks that actually work become, well, just stuff we do. So how do the trendy kind of biohacks stack up against more boring, established alternative practices?

Longevity is one of the biggest buzzwords in biohacking right now, and yet it all feels very off-the-mark to me. Much of the chatter is based on mouse studies and blood-based biomarkers, and the associated hacks include things like fasting and cold exposure.

I actually visited one of the blue zones famed for their populations of 100-year-old residents (Nicoya, Costa Rica, where centenarians arent common, but are less rare than in other parts of the world). The biggest thing I took away from that experience is that if you want to live a long time, it really helps to live in a place with near-universal healthcare that does a lot of outreach to older and rural populations.

You cant biohack your way into being born in 1920s Costa Rica. But people who idolize the blue zones end up hypothesizing that maybe its this about the food, or this about the water, or that about the type of exercise people get while doing farm work. (Fun fact: lard and fruit juice both figure heavily into the traditional diet; good luck getting any biohacker on board with both of those.) In truth, maybe its a combination of genetics and culture, and perhaps even a few-decades-long statistical luck of the draw.

In short, its impossible to thoroughly study human longevity in timeframes that are less than a human lifespan. What pass for longevity biohacks tend to be based on wishful thinking and a fear of disability or of growing old enough to get (gasp) wrinkles. And they mostly amount to confirmation bias: Whatever makes you healthier should help you live longer, right? So whatever you have already decided is a healthy habit (or biohack), thats what youll tell your biohacking buddies is a pathway to longevity.

Keto (low carb) diets and intermittent fasting are two dietary strategies most often used to lose weight, although sometimes the stated goal is to give you more energy or to promote health and boost longevity.

Both of these strategies can help a person to lose weight or to become healthier, sure, but not because either is a cheat code. For a while there was a hypothesis that putting your body into a state of ketosis from eating very little sugar or starch would change how hungry you feel, and thus how much fat you store. It was an interesting hypothesis, but research has repeatedly failed to find any such effect. (Take this recent study, for example.)

Intermittent fasting is in a similar place. Its definitely one of many effective strategies one can use when dieting. If you want to bring your weight down a few pounds, you might rather have no breakfast and a big lunch, than a small breakfast and a small lunch. But is the practice worthwhile? If you enjoy it, sure. But there isnt any compelling evidence a person who fasts frequently is going to be healthier in the long run than a person who eats a healthy diet at normal mealtimes.

Once again, were back to the reality that there is no best diet, but a broad set of principles (get some protein, eat your vegetables, create a calorie deficit if youre trying to lose weight) that you dont need special hacks to live by.

Biohackers love to talk about their mental state. Does this or that supplement help you focus? How can you be best primed to pay attention and learn things more quickly and understand them more deeply?

In a sense, self-experimentation on a subjective mental benefit is easy. Do the thing, and see if you feel more focused. But on the other hand, subjective mental outcomes are the most susceptible to the placebo effect. Maybe youre focusing better because you feel like youve created the optimal environment for you to focus better, and that in itself lets you focus better. One study on microdosing found results consistent with the idea that this may, in fact, be exactly whats happening.

Various drugs, supplements, and techniques (like taking a cold shower before you study) might help us focus. But I think its important to consider who has already asked this question, without calling it biohacking? In this case: students. How do you study more effectively?

Well, caffeine can definitely help. (Research shows the stimulant does seem to help you focus, even aside from its benefit in keeping you awake during your study session.) Creating an environment where you wont be distracted or disturbed can also be helpful. I can even look around me now, as Im writing this, to see a number of things I could rebrand as biohacks: Ive got a caffeinated beverage, noise-canceling headphones, and an exercise bike (since my workday goes better when I get exercise in the morning, even if only a few minutes). Theres also the notebook thats always within reach, since I find pen and paper brainstorming and to-do lists more effective than their digital counterparts.

Focus biohacks blur pretty seamlessly into study tips. Remember that, or else youll end up like the aspiring pianist who showed up on the biohackers Reddit looking for focus hacks while dismissing the idea that they should perhaps be asking piano Reddit about the best ways to practice.

Sleep is important, and we all need to get enough of it. Sleep-related biohacks are some of the most talked about (probably second only to those concerning diet) because sleep effects so many areas of our lives. If you dont get adequate sleep, youll be tiredmaking sleep also a biohack for focus.

But there arent really any shortcuts to getting enough sleep save for...getting enough sleep. Years ago there was an idea that you might be able to take six small naps a day and never need spend a whole night asleep; none of the people who sung its praises managed to stick with it, strongly suggesting that it was not, in fact, a sustainable alternative.

The rest of the sleep hacks tend to fall into two categories: youre either re-discovering ordinary sleep hygiene stuff (making your sleeping area a cool, dark, quiet place and getting to it on time each night), or youre obsessing over sleep stages and body functions detected by a smartwatch or a gadget like an Oura ring.

As much as I eschew most of the trendy biohacks, I do wear an Oura ring. I use it for two things: noticing how many hours I was in bed, and making sure my resting heart rate drops down to its usual baseline when I take a rest day from exercise. What I dont do is pay one iota of attention to how much REM or deep sleep it thinks Im getting, or scour biohacking websites for ways to improve my heart rate variability.

Even the best consumer gadgets just arent great at differentiating one sleep stage from another (my ring rarely credits me with more than an hour of REM sleep in a given night) and obsessing over whether youve got a good HRV score is not a worthwhile hobby. Do you feel well-rested? Have you been under a lot of mental or physical stress lately? You can answer those questions on your own. A sleep tracker just gives you a more precise way to say Im tired.

I feel the same way about biohacking as I do about gamifying health and fitness. You have to look at your real problems or goals, and decide on real solutions, instead of getting distracted with metrics or tweaks that ultimately dont make a difference. For any goal with broad appeal, others have been in the field finding solutions for far longer than anybody who has been calling it biohacking. Want to prevent cancer, for example? The American Cancer Society has plenty of tips for you.

The biohackers who show up on forums asking how to increase muscle protein synthesis (or even the grinder who tried to genetically engineer his own arm muscles) would be better served by consistently lifting some heavy shit. People have built huge muscles with nothing but weight training and a high protein intake. Those who do this, have great genetics, and also take steroids have built even bigger ones.

Steroids are a biohack by any definition, but their dangers and side effects are well-known. Part of the thrill of being into biohacking is that youre constantly digging up new ideas whose potential effectiveness is as big as your imagination, and whose downsides are not yet known. Reality is a lot more disappointing.

The rest is here:
What Is Biohacking, and Is Any of It Not Stupid? - Lifehacker

Amyotrophic lateral sclerosis (ALS) has a devastating trajectory, first manifesting as muscle weakness and slurred speech. From there, it steals progressively more motor function until sufferers are no longer able to breathe on their own. There is no cure, and treatments can only prolong the inevitable by months, at most.

Most patients die within two to five years, although there are exceptions: theoretical physicist Stephen Hawking famously lived more than 50 years with the disease. Another striking case: The Indigenous population of Guam in the years after World War II, which developed ALS in very high numbers for unknown reasons.

Unlike typical ALS patients, many Guamanians with the disease lived a long time without medical intervention 20 years or more. Reports indicate the more severe the symptoms at onset in the Guamanians, the longer they lived the opposite of modern patients.

Risana Chowdhury, a doctoral candidate in anthropology, is looking to discover why.

Risana Chowdhury, a doctoral candidate in anthropology, conducts an immune-assay to determine the levels of c-reactive protein in the sera of Guamanian ALS patients and matched controls. Image Credit: Provided photo.To that end, she is looking at a panel of immunoregulators in human serum from Guam that is part of Binghamton Universitys biospecimen archive, under the direction of Chowdurys mentor, Professor Ralph Garruto. Her focus is on c-reactive protein (CRP), a marker of inflammation produced by the liver, and cytokines, which regulate immune function. As with most diseases, elevated levels of inflammation are part of ALS.

I am interested in how serum inflammation may have been different in Guamanian ALS patients compared to modern ALS patients, and how these differences may have influenced the unusually long lifespan seen in some cases of Guamanian ALS, she said.

Born in Bangladesh, Chowdhury moved to the United States at the age of five; she grew up mostly in Missouri. Originally contemplating a career in dentistry, she came to Binghamton with her husband a resident in internal medicine at the time and decided to pursue a masters degree in biomedical anthropology. The field proved so interesting that she shifted gears during her masters program and decided to become an anthropologist herself.

I think biological anthropology is fascinating because it is the study of humans interacting with their environments. It observes how one affects the other and how human behaviors, on both individual and community levels, affect health outcomes, she said.

She completed her MS in 2009 and enrolled in the MA/PhD program in 2015, completing her MA in 2018. Life has been busy in other ways, too; she had three children during the course of her studies at Binghamton.

She has found the University to be a welcoming and supportive environment, from her professors and department staff to the undergraduate students who have assisted her research through the years; many of the latter have gone on to their own graduate programs or to medical school. Chowdhurys research also received a boost from internal grants, including one from Harpur Edge.

My female and BIPOC (Black, indigenous and people of color) professors have also inspired me. I know it sounds clich, but representation matters! she said.

Her advisor, Associate Professor Katherine Wander, helped Chowdhury formulate hypotheses for the project. The central premise is this: Because humans have co-evolved with parasites and infectious diseases, our ancestors immune systems learned to self-regulate based on these interactions. Intestinal parasites, for example, down-regulate the hosts immune response in order to survive. Higher-income countries have significantly reduced childhood exposure to such pathogens, which can result in a hyperactive immune system in turn leading to an increased risk for developing allergies and autoimmune diseases later in life.

ALS emergence on Guam is a mystery; when the Spanish ruled the island from the mid-1500s to 1898, they made no note of it. The incidence of ALS has also decreased since the modernization of the Pacific Island, with the last remaining cases affecting between 10 and 25 individuals occurring between 1980 and 1991.

Risana Chowdhury, a doctoral candidate in anthropology, explains one of the three pilot studies she conducted to ensure the integrity and reliability of her data. Image Credit: Provided photo.According to reports, the environment of post-World War II Guam was higher in parasitic and other infectious diseases. My question is: Did Guamanians with ALS live longer because their exposure to a higher-infectious disease environment made their immune systems stronger? Chowdhury said. Studying patterns of inflammation in Guamanian sera of ALS cases and non-cases may help us answer that question.

So far, she has uncovered surprising patterns in the data that support the findings of researchers from the 1950s, although its too early to come to meaningful conclusions.

In the Guamanian ALS cases, elevated serum levels of some pro-inflammatory cytokines appear to be associated with longer lifespan. This is different from modern ALS cases, where higher serum inflammation is associated with shorter lifespan, she said.

Chowdhury is currently in the process of writing her dissertation, which she plans to defend in May 2022. She hopes to continue teaching or conducting research in the field.

Weve lost several giants in anthropology these last few years, including our own Professor Gary James in 2020 and well as E.O. Wilson and Richard Leakey more recently. Those are enormous shoes to fill, but it would be incredible to carry on their legacy, while taking anthropology to broader and more inclusive horizons, she said.

Read more here:
Research explores longevity and ALS | Binghamton News - Binghamton University