Category Archives: Human Longevity

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TEL AVIV, Israel--(BUSINESS WIRE)--Nucleai, a leader in AI-powered spatial biology transforming precision medicine by unlocking the power of pathology data, today announced the appointment of Kenneth J. Bloom, MD, FCAP as the companys new head of pathology. Dr. Bloom brings more than 35 years of clinical experience in pathology, oncology, telemedicine and bioinformatics to this critical role at Nucleai.

In his most recent role, Dr. Bloom was Chief Medical Officer of Advanced Pathology and Genetic Services at REALM IDx, including operating companies: Invicro and Ambry Genetics. Previously, he was President and Head of Oncology and Immunotherapy for Human Longevity Inc. In this role, Dr. Bloom was responsible for all sequencing products and for establishing and leading the Oncology program. Under his direction, the team developed and commercialized an industry-leading cancer exome product and commercialized a technique for validating neoantigens predicted from sequencing.

Earlier in his career, he spent 12 years as a top executive at Clarient Pathology Services where he led the development of hundreds of laboratory-developed tests, including those using IHC, ISH, Flow Cytometry and molecular methods. He has also served as a principal investigator in more than a dozen clinical trials and as an advisor to various pharmaceutical and biotech companies. Before his industry experience, Dr. Bloom spent 15 years at Rush Medical Center.

I am excited to welcome Dr. Ken Bloom, a world-renowned thought leader in pathology, to our team. His experience, knowledge and innovative ideas are an asset for Nucleai, said Avi Veidman, CEO of Nucleai. The appointment of Dr. Bloom as the Head of Pathology strengthens our ability to unlock the power of pathology data through our AI-driven spatial biology platform. As we have assembled a team of world-class physicians, scientists and technologists, Nucleai is uniquely positioned to help advance precision medicine more rapidly.

Nucleais state-of-the-art spatial biology and machine learning platform empowers researchers and pathologists to improve workflows and unleash data previously hidden within pathology slides, transforming the practice of pathology and improving patient outcomes, said Dr. Bloom. I look forward to working with Nucleais CEO and other visionaries within the company to make Nucleais approach pervasive in the medical field.

About Nucleai

Nucleai is an AI-powered spatial biology company with a mission to transform drug development and clinical treatment decisions by unlocking the power of pathology data. Nucleai provides pharmaceutical companies, contract research organizations, and diagnostics laboratories with a state-of-the-art AI platform to improve clinical trials and clinical decision-making. For more information, please visit http://www.nucleai.ai.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220802005702/en/

Anthony PetrucciBioscribe[emailprotected]512-581-5442

Source: Nucleai

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Nucleai Appoints New Head of Pathology to Support Expansion in Biopharmaceutical and Clinical Markets - StreetInsider.com

Healthy aging is a shared goal of most humans, but the body has a nasty habit of breaking down over time. Tantalizing research suggests it is possible to develop nutrition and lifestyle interventions that can delay aging and extend healthspan. In model organisms, including rodents and nonhuman primates, caloric restriction (CR) has proven to be an effective method for mitigating aging-related deterioration of biological functions and for extending healthspan and lifespan. But more than 80 years since its discovery, the underlying mechanisms by which caloric restriction extends either are still largely undefined.

Researchers have linked a number of biochemical pathways to longevity, including those involved with nutrient signaling, metabolism, growth, genome stability, and oxidative stress. Translating this knowledge, derived mostly from mouse studies, to humans is an additional barrier that must be overcome. For example, it is almost impossible for the majority of people to maintain severe dietary restriction over their lifetime. Thus, more viable solutions for promoting health- and lifespan in humans must be found.

We have been studying the behavioral effects of CR in mice and have found that it leads to dramatic changes in feeding behavior. In contrast to mice given continual access to unlimited food, which spread their daily food consumption over the course of the day and night, mice on caloric restriction adopt a stark feeding and fasting pattern in which they consume all of the food provided within a few hours each day. Thus, under CR, mice not only consume fewer calories, they voluntarily adopt a time-restricted feeding pattern with a long fasting interval. All these factors have been shown to have numerous health benefits, again primarily in animal models.

More than 80 years since its discovery, the underlying mechanisms by which caloric restriction extends lifespan are still largely undefined.

To disentangle the contributions to longevity of calorie restriction, periods of fasting, and alignment of eating with an animals circadian clock, we recently completed a comprehensive study that contrasts these three factors. We found that CR is sufficient to extend lifespan but that the pattern and circadian alignment of eating act synergistically to extend lifespan further. While CR alone increases lifespan by approximately 10 percent, eating that CR diet only at night, when mice are normally awake, extends lifespan by more than 35 percent compared to mice eating regular diets. We also found that circadian alignment of feeding enhances CR-mediated benefits for survival independently of fasting duration (2 vs. 22 hours) and body weight. Aging promotes increases in inflammation and decreases in metabolism in the livers of mice with constant access to food, whereas a CR diet fed at night ameliorates most of these aging-related changes. Thus, eating only at certain times of day appears to promote longevity in animals and could provide a new mechanism for the treatment and management of aging in humans.

A significant aspect of our study was that there were no significant effects of the pattern or time of eating on body weight in mice. In addition, body weight was not associated with lifespan. This finding is consistent with a recent report in the New England Journal of Medicine (NEJM) comparing weight loss in two groups of human subjects that were assigned to CR alone or CR with an 8-hour time-restricted eating window. The authors of this paper report no differences between these groups and conclude that there was no benefit of time-restricted eating for body weight. As we showed in our study, however, body weight does not serve as a good biomarker for longevity under CR conditions. So it would have been more useful in the NEJM study to have measured other endpoints besides body weight, such as inflammatory biomarkers associated with aging. In addition, previous studies that demonstrated health benefits of time-restricted eating were performed under conditions of overeating, not CR. Obviously, CR and overeating engage fundamentally different metabolic processes, and thus time-restricted eating of a CR diet should not be expected to yield the same results as time-restricted eating of a calorie-rich diet.

Our discovery that CR functions in concert with time-restricted eating and circadian alignment to optimally extend healthspan and lifespan is potentially transformative because it may yield a novel method for promoting healthy aging and lifespan increases in humans. Because lifespan in humans is primarily determined by lifestyle (less than 25 percent is genetically determined), these findings may be translated in future work to humans and are amenable to widespread adoption because they can be achieved by behavioral intervention: a CR diet eaten at the correct circadian time of dayi.e., when one is normally awake. This might involve, for example, a 12-hour eating window that begins at breakfast time.

A significant aspect of our study was that there were no significant effects of the pattern or time of eating on body weight in mice.

In addition, ongoing research in our labs seeks to test whether enhancing circadian clock function by behavioral (lifestyle), genetic, or pharmacological means can delay the aging process. Pharmaceutical agents were identifying in our labs that enhance circadian clock function may one day be used in humans as comprehensive therapies for aging. For now, were planning experiments for testing their anti-aging and pro-longevity effects in mice. Our lab and others have already provided evidence that the circadian clock system is an upstream regulator of all of the known anti-aging and pro-longevity pathways. So enhancing circadian clock function may rescue multiple aging pathways at the same time. We are testing this hypothesis by boosting Clock gene expression in genetically engineered mice. These animal studies can then lay the groundwork for the isolation of small molecules that target the Clock protein and the development of drugs that might safely modulate clock function and enhance health and longevity in people.

Joseph S. Takahashiis an investigator in the Howard Hughes Medical Institute and professor and chair of the Department of Neuroscience at the University of Texas Southwestern Medical Centers Peter O Donnell Jr. Brain Institute. He is also a member ofThe ScientistEditorial Advisory Board. Carla B. Green is a professor and Distinguished Scholar in the Department of Neuroscience at the same institution.

The rest is here:
Opinion: Changing When and How Much We Eat May Extend Health Span - The Scientist

Wards wry survey of the weird world of immortalism goes heavy on the early history of cryonics (freezing corpses until we work out how to revive them) but it is light on the science of what we actually know about ageing. To fill this gap, at least partially, I recommend Methuselahs Zoo () by the zoologist Steven M Austad.

Austads big beef and hes not alone in this is that too many experiments are done on mice. For anyone interested in ageing, the trouble with mice is that they dont live very long, even relative to their size. Which terrestrial mammals live the longest? The answer to this, funnily enough, is humans. As Austad points out, mice should really be experimenting on us.

The rationale of this smartly written book can be summed up by whats known as Orgels second rule, after the British chemist Leslie Orgel: namely, that evolution is cleverer than you are. So if you want to know how to extend the longevity of humans, one way might be to examine the superior longevity of other animals, then try to work out how they manage it.

As weve seen, this is tricky, since humans already have a high longevity quotient, yet there are animals that outdo us and this gives Austad his cue for an entertaining tour of the whole animal kingdom in all its mad variety. I had no idea I would so enjoy reading about the naked mole rat, or indeed the human fish, a type of salamander that lurks in Balkan caves.

The one disappointing thing about this urbane volume is that even though Austad knows more about his subject than anyone on the planet, on the key points he still doesnt know much. His chapters often end by asking rhetorically what lessons we have learnt from the exceptional longevity of such-and-such a beast only to conclude that, as yet, the answer is none. More research is needed.

Specifically, Austad recommends we trigger a Manhattan Project to uncover the longevity secrets of birds. Or bats, for that matter. In this, he brings to mind Nikolai Fedorov, the Russian philosopher and godfather of immortalism, who argued in the 19th century that the quest to combat death should be put on a war footing.

Now that Jeff Bezos and other multi-billionaires have put their financial heft behind the quest to understand ageing, this may be what were getting. For anyone with cash to spare, Id recommend channelling some of it towards the katabatic heroes at the London Institute for Mathematical Sciences. New technologies often originate in identifying and harnessing new scientific principles. In this case, the researchers would be descending into the unknowns of lifes thermodynamics and a theory of immortality.

Like the Greek hero Pirithous, who failed to make it back from hell, they might never be seen again. On the other hand, theres a chance they might return with quite a story to tell.

To order a discounted copy of either book call 0844 871 1514 or visit Telegraph Books

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Some species are immortal but dying of old age is humanity's secret weapon - The Telegraph

From a cup of caffeine to the exact shade of your vegetable, from how much and what kind of exercise you should do to whether broccoli is doing you more harm than good, the era of personalised food, fitness, and medicine is here.

That's the greatest thing that can happen and is a solution that will ultimately help people to live long, says Sajeev Nair, the Co-founder and Chairman of Vieroots Wellness Solutions.

Founded in 2019 by Sajeev and Co-founder Adityanarayan, Bengaluru-based healthtech startup Vieroots Wellness Solutions has pioneered the Artificial Intelligence (AI) powered and Personalised Epigenetic Lifestyle Modifications (EPLIMO) mobile app.

Our goal is to healthfully transform the lives of one crore people through EPLIMO by 2025, Sajeev says.

"As COVID-19 made people realise that they need to take charge of their own health, they started searching for tools and processes to do it. EPLIMO was on time in the market as a solution to their search," he adds.

With the option to store healthcare records for quick reference and locate nearby practitioners, EPLIMO puts everything at its users fingertips.

As COVID-19 altered the dynamics of health and healthcare, bringing several technological interventions in its wake, the pandemic also induced a long-term shift in consumer behaviour and attitudes, redefining relationships with the body and the mind.

The earlier approach of reactionary medicine, as Sajeev calls it visiting a doctor only in times of sicknesshas been steadily changing owing to a quick shift towards slow and sustainable living, and a holistic transformation in lifestyle choices.

The shift is towards long-term solutions and as Sajeev calls it, an early adoption of preventive medicine/preventative healthcare.

In fact, according to Indian market research firm, Numb Research, Indias 443 million millennials spend an average of Rs 4,000 per month on health and wellness services and products.

This is validated by the 5,000+ active user base of EPLIMO, a steadily growing tribe.

More than 200 lifestyle coaches and 500+ wellness consultants are on board with Vieroots.

At one point in time, I used to consume a lot of nutritional supplements and exercise a lot, but I soon learnt that not everything is for everyone. I learnt that some of these supplements can do more harm than good, while some of the exercises can actually kill you. And, that was a big revelation, Sajeev recalls.

In 2005, when I had gone to the US I came across a concept called nutrigenomics (also known as nutritional genomics, the term is broadly used to define the relationship between nutrients, diet and gene expression), which is to primarily decode nutritional aspects based on genomics, he says.

In 2003, the Human Genome Project was completed.

Sajeev soon learnt that one would be able to decode the diverse nutritional requirements of the body based on the DNA.

Hailing from Kerala, serial entrepreneur Sajeev, a well-known wellness evangelist and one of Indias first biohackers, was already working on his wellness business at that time.

The author of The Making of a Superhuman, Sajeev experimented on himself some of the DIY biohacks or personalised lifestyle modifications that he came to understand through his research.

As he started cultivating the space of long healthy fulfilling lives, he soon discovered how it was intrinsically connected with personalised health.

Typically, a customer is delivered a kit enabling them to take 2 ml of their saliva, and the sample is reverse-picked and dispatched to the genomic lab. The lab then decodes ones DNA and assesses it across the metrics of 250 different health conditions.

The DNA report card lets a user receive a host of information: from their risk to lifestyle diseases like diabetes as well as autoimmune diseases to how minerals and vitamins are getting absorbed in their cells and their musculoskeletal structure generativity.

However, Vieroots soon realised that it was not enough.

Imagine when you visit a good doctor for a certain condition or any illness. They sometimes ask seemingly unrelated questions regarding sleep cycle etc. To a lay person, it might seem unrelated, but Sajeev explains that these are deeper questions directly related to ones body and health. For example, whether one is getting good sleep or not is also a determinant of their digestive function.

Vieroots curated a questionnaire of 70 metabolism-related questions, pre-loaded onto their mobile app, EPLIMO. When a user visits the website they are directed to the app, and when they download the app, the user is directed to answer these questions.

Sajeev gives an example: Suppose if you look at a genomic report, an individual might genetically have a higher risk for lactose intolerance. To address the issue of lactose intolerance, the suggested recommendation must be in the nature of don't use dairy products. However, once you go read through the report further, maybe, you will find a higher risk for lower concentrations of calcium, and the stated recommendation would be consume more of calcium-rich foods like milk.

The correlation is missing; the report is only based on condition-to-condition parameters. EPLIMO claims to provide a highly accurate recommendation by correlating the various conditions using the power of ML and AI.

Sajeev describes the personalised health bulletin as an operating manual for the rest of your life as genomic data never changes.

The good thing is that our target group is very defined; they are health-conscious people. We are only targeting people who are already health-conscious, but making mistakes. For example, people who need to make informed choices, be it in exercise or diet, Sajeev explains.

So far, the number of app downloads stands at 5,500 with Tier I comprising 70-80% and the Northeast comprising up to 20%. The average age profile of the user base is between 25 and 55 years.

The entire EPLIMO process, including the counselling and coaching, costs Rs 30,000 plus taxes.

Vieroots has trained wellness or lifestyle coaches with a background in life sciences. Some of them are dieticians, and professionals who have pursued biotechnology courses. All work on a commission basis for generating and supporting sales.

The lifestyle coaches undergo a two-month course, for which Vieroots has affiliated with the Indian Association for Functional Medicine.

The entire process takes about four weeks to six weeks, starting from the delivery of the genomic kit through to the counselling session. The final virtual counselling session takes place in addition to the PDF-format epigenetic personalised lifestyle recommendation manual that the user receives on the app.

Talking about the challenges, Sajeev explains, The first name that comes to a users mind when we talk about healthcare is the doctor. And, yet, you normally visit a doctor when you are sick. Also, most doctors do not have the time or bandwidth to look into preventive healthcare, because they are too busy working on diseases.

In the case of autoimmune diseases, the only medicine available is immunosuppressants. Some genomic report findings have revealed that for some people, nightshade vegetables, the likes of tomatoes and potatoes, have an adverse effect. And interestingly, it was observed that when such people stopped consuming them, their autoimmune disease, for which they have been suffering for years, also subsided, he adds.

Sajeev says that there are no direct competitors or services like EPLIMO. However, he names some of the top players in the "personal genomics market" in India: MayMyGenome, Genebox, and Medgenome.

The bootstrapped startup follows the direct-to-customer revenue model.

We completed a full financial year this year on March 22, and locked in Rs 14.8 crore with a narrow profitability. We have two revenue streams: one is a service, and the second is our nutritional supplements, Sajeev states.

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Vieroots uses genome testing to win over a growing tribe of wellness enthusiasts - YourStory

The existence of the human body is incredibly intriguing and lovely. Many physical processes and defence mechanisms that keep the body safe and healthy are part of who we are naturally. Our skin is same, even.

Therefore, using natural products is the ideal method to enhance the natural properties of skin, and what better way to achieve it than by utilising the superpowers of the legendary Ayurveda! In India, Sri Lanka, and other South Asian countries, the ancient medical system known as Ayurveda is still used today.

The use of Ayurvedic cosmetics was intended to promote longevity and excellent health in addition to improving one's outward beauty. There are many Ayurvedic skin care formulae available today, but in order to get the best results, it's important to know the quality and ingredients of your products.

Haldi (Turmeric)

We all know the benefits of Haldi when it comes to our food but do you know it is also extremely good for our skin. Turmeric contains curcumin, which has anti-aging, anti-inflammatory and anti-bacterial properties. As a result it increases the natural glow and radiance of your skin.

Chandan (Sandalwood)

Sandalwood is an essential Ayurvedic plant that is utilised in many Ayurvedic herbal products. This ancient ingredient contains cooling properties as well as organic brightening components that help heal sun tans, black spots, and uneven skin tone.

Giloy (Heart-leaved Moonseed)

Giloy is an antipyretic herb loaded with antioxidants, which helps to reduce oxidative stress hence delaying skin aging. It also has anti-inflammatory properties that assist in skin tissue regeneration and inflammation reduction.

Amla (Indian Gooseberry)

Amla, or Indian gooseberry, is abundant in Vitamin C and antioxidants, making it a good anti-aging herb. It tightens your skin and gives it a healthy glow. Regular drinking of amla juice increases the collagen production in your skin. External use of Amla extracts in the form of face packs and washes helps to prevent acne, pimples, sunburn, and other skin disorders.

Neem

Neem is another beloved medicinal herb in South-Asian countries. The antibacterial, anti-inflammatory, antioxidant, and therapeutic effects of neem leaves and extracts are the reasons for its popularity. It can be used to treat acne and dry skin. Since it stimulates collagen production, it can also help reduce wrinkles and reduce scars.

Kumkumadi Tailam

KumkumadiTailam is an Ayurvedic natural oil with a bunch of brilliant medicinal properties. Its blessings for the pores and skin are extraordinary. It can lessen wrinkles and different symptoms and symptoms of aging, minimise zits and acne, or even deal with pores and skin situations like allergy and more. It additionally reduces melanin formation, lightening the general pores and skin tone and lowering darkish patches.

Since this Ayurvedic oil is antibacterial and anti-inflammatory, it may heal minor wounds at the pores and skin. Moreover, the lac gift as one of the components is an effective antifungal agent, which prevents a bigger variety of infections.

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Herbs radiate and give you youthful skin - The Hans India

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Everything in America is getting older these days. In practically every field of human endeavorpolitics, business, academia, science, sports, pop culturethe average age of achievement and power is rising.

Politics is getting older. Joe Biden is the oldest president in U.S. history. Remarkably, he is still younger than House Speaker Nancy Pelosi, House Majority Leader Steny Hoyer, and Senate Minority Leader Mitch McConnell. And they arent exceptions to the general rule: The Senate is the oldest in history.

Businesses are getting older. The average age of new CEOs at Fortune 500 companies is very likely at its record high, having gradually increased throughout the 21st century. And its not just the boss; the whole workplace is getting older too. Between the 1980s and early 2000s, Americans under 45 accounted for the clear majority of workers. But that's no longer the case, since the large Baby Boomer generation has remained in the labor force longer than previous cohorts.

Science is getting oldernot just in this country, but around the world. Discovery used to be a young persons game. James Watson was 24 when he co-discovered the structure of DNA, and Albert Einstein was 26 when he published his famous papers on the photoelectric effect and special relativity. But in the past few decades, the typical age of scientific achievement has soared. Nobel Prize laureates are getting older in almost every discipline, especially in physics and chemistry. The average age of an investigator at the National Institutes of Health rose from 39 in 1980 to 51 in 2008, and the average age of principal investigators receiving their first major NIH grant increased from about 36 in 1990 to about 45 in 2016. In fact, all of academia is getting older: The average age of college presidents in the U.S. has increased steadily in the past 20 years. From 1995 to 2010, the share of tenured faculty over the age of 60 roughly doubled.

In pop culture, the old isnt going out of style like it used to. The writer Ted Gioia observed that Americans have for several years shifted their music-listening to older songs. In film, the average age of movie stars has steadily increased since 1999, according to an analysis by The Ringer. So far this year, the seven highest-grossing American films are sequels and reboots. Sports such as tennis and football are dominated by superstars (Nadal, Djokovic, Brady, Rodgers) who are unusually old for the game. Incredibly successful young artists and athletes obviously do existbut older songs, older stars, and existing franchises are dominating the cultural landscape in a historically unusual way.

So, whats going on?

1. As rich Americans live longer and healthier lives, American power is aging.

The average American lives longer than they did in 2000, despite life expectancy flatlining in the past decade. Rich Americans have it even better: The wealthiest Americans live at least 10 years longer than the poorest Americans, and that gap is growing.

Since the rising ages of prominent politicians, CEOs, and Nobel Prize winners are whats at issue, a focus on the elite seems appropriate. For most of this century, the richest quartile of men have been adding about 0.2 years to their life expectancy each year. If we extrapolate that annual increase to the entire century, it would suggest that rich men have added roughly four years to their lifespans since 2000. The average age of U.S. senators did, in fact, rise from 59.8 in 2001 to 64.3 in 2021a roughly four-year increase.

But many positions and institutions are getting older much faster than that. A few years ago, Inside Higher Ed noted that for college presidents, 70 seems to be the new 50.

The average age of new CEOs at Fortune 500 and S&P 500 companies increased nine years since 2005from 46 to 55. The average age of leading actors in films increased about 12 years since 2001from about 38 to about 50 for male stars.

Maybe we should consider not just life spans, but health spans. In sports, for instance, a superior understanding of diet, exercise, and medicine has allowed stars to extend their careers. The tennis stars Novak Djokovic, 35, and Rafael Nadal, 36, are old for their sport, but theyve somehow won 15 of the last 17 Grand Slam mens tournaments. Three of the last five NFL Most Valuable Player Awards went to quarterbacks over the age of 36Tom Brady in 2017 and Aaron Rodgers in 2020 and 2021. In basketball, LeBron James recently became, at 37, the oldest NBA player to average 30 points per game in a season. The winningest pitcher in Major League Baseball is Justin Verlander, who is 39.

So the longevity factor is twofold. Not only are Americans overall living longer, but richer Americans are living even longer, and rich Americans with access to dietitians, personal exercise, and high-class medical care are extending their primes within the context of longer lives. As a result, we should expect older workers to vigorously contribute to their fields much longer than they used to.

2. As work becomes less physical and more central to modern identity, the old elite are spending more time at work.

Another way to frame the central question here: Why are the Boomer elite working so hard, so late into their lives?

One explanation for the rapid aging of our political leaders, academic faculty, and chief-executive class is that the Boomer generation is choosing to stay in the workforce longer than previous generations did. This has created what the writer Paul Millerd calls a Boomer blockade at the top of many organizations, keeping Gen-X and Millennial workers from promotions. As older workers remain in advanced positions in politics and business, younger workers who would have ascended the ranks in previous decades are getting stuck in the purgatory of upper-middle management.

If one wanted to frame things more generously, one could say that declining ageism has allowed older Americans to stay in jobs that they really like and dont want to leave. These folks could retire, but they love their work and draw an enormous amount of pride from their careers.

But 70- and 80-somethings loving their work so much that they never retire is awfully close to something Ive called workismthe idea that work has, for many elites, become a kind of personal religion in an era of otherwise declining religiosity. Workism isnt all bad; its nice that the economy has evolved from brawn to brainy labor that gives people a sense of daily enrichment and higher purpose. But workism isnt all good, either: The corner office was not designed to function as a temple, and a work-centric identity can lead to a kind of spiritual emptiness. Whats more, though this subject is complicated and sensitive, a lot of very elderly people in positions of great power are clinging to their jobs long after their cognitive and verbal capacities have peaked. This is not a good recipe for high-functioning institutions.

3. The burden of knowledge: Science is getting older, because were all getting smarter.

Longer lives and increasing workism could explain why our political and business leaders are quickly getting older. But they dont explain the biggest mysteries Ive highlighted in the field of sciencesuch as why the average age of Nobel Prize laureates has increased or why young star researchers are rarer than they once were.

The best explanation for both of these trends is the burden of knowledge theory. We are learning more about the world every year, but the more we learn about any subject, the harder it is to master all the facts out there and push the frontier of knowledge outward.

This theory is pretty obvious when you think about it for a few seconds. Lets imagine, for example, that you want to revolutionize the field of genetics. Three hundred years ago, before any such domain existed, you could have made a splash just by shouting, Ive got a strong feeling that genes are a thing! Two hundred years ago, you could have done it by watching some peas grow in your backyard and using your powers of observation to form a theory of inheritance. But now that we know that genes are a thing and have figured out dominant and recessive genes and have mapped the genome, the most groundbreaking research in the field is really, really complicated. To understand the genetic underpinnings of a complex disease such as schizophrenia, hundreds of people around the planet have to synthesize data on the infinitely complex interplay of genes and environment.

The burden of knowledge affects the average age of scientists in several ways. First, attaining mastery at a young age of an existing domain becomes harder. Since scientists have to learn so much in fields such as physics or chemistry, they take longer to become established, and the average age for achieving breakthrough work (or fancy prizes) goes up and up. Second, the knowledge burden necessitates large teams of researchers to make new breakthroughs, and these teams tend to be led by older principal investigators. Third, scientific-funding institutions, such as the National Institutes of Health and National Science Foundation, may be awarding a disproportionate amount of funding to older researchers precisely because theyre biased against younger researchers who they assume havent overcome the knowledge burdens of their field. Or perhaps, as academia and funding institutions get older, they develop an implicit ageism against younger researchers, who they assume are too naive to do paradigm-shifting work in established domains.

The burden of knowledge theory represents a double-edged sword of progress. It is precisely because we know so much about the world that it is getting harder to learn more about the world. And one side effect of this phenomenon is that science is rapidly aging.

4. Data dulling has made institutions risk-averse (and consumers obsessed with familiarity).

Pop culture in 2022 has been a warm bath of nostalgia. The song of the summer is quite possibly Kate Bushs Running Up That Hill, which was originally released 37 years ago. Its success was launched by the show of the summer, the 80s pastiche Stranger Things. The years biggest blockbuster, Top Gun: Maverick, is a sequel-homage to the 1986 original.

Okay, well, thats just one summer, you might be inclined to say. But its not. So many recent albums have fallen short of expectations that The Wall Street Journal has called it a new music curse. Every year in the last decade, at least half of the top-10 films in America have been sequels, adaptations, and reboots. (Even the exceptions are their own sort of franchise: The two biggest opening-weekend box offices for original films since 2019 were for movies directed by Jordan Peele.)

Is this about median longevity, or workism, or the burden of knowledge in physics and genomics? Uh, no. These are cultural stories, and they deserve a cultural explanation. The best Ive got is this: As the entertainment industry has become more statistically intelligent, entertainment products have gotten more familiar and repetitive.

In music, Ive previously called this the Shazam effect. As the music industry got better at anticipating audience tastes, it realized that a huge portion of the population likes to hear the same thing over and over again. Thats one reason why hit radio stations have become more repetitive and why the most popular music spends more time on the Billboard charts.

For the past few decades, the same statistical revolution that reshaped sportsa.k.a. moneyballhas come for entertainment. You could call it data dulling: In entertainment, greater algorithmic intelligence tends to ruin investment in originality. When cultural domains become more statistically sophisticated, old and proven intellectual property takes money and attention from new and unproven acts.

What does data dulling look like in art? It looks like music companies spending hundreds of millions of dollars buying the catalogs of old hitmakers when, in previous generations, that money would have gone toward developing new artists. It looks like movie studios spending significantly more on the production budgets of sequels than on originals. It looks like risk-averse producers investing more in familiar content, which amplifies consumers natural preference for familiaritythus creating a feedback loop that clusters new cultural products around preexisting hits. It looks a lot like what weve got.

***

Americas multidisciplinary gerontocracy is complex. It comes from a mix of obviously good things (were living longer, healthier lives), dubiously good things (an obsession with the music and tastes of the 1980s), and straightforwardly bad things (a stunning dearth of young political power and an apparent funding bias against young scientists).

Solving this problem is similarly complex. I would be very uncomfortable with laws that ban ambitious 74-year-olds from working. Im not very interested in forcing Bruce Springsteen fans to stop listening to him. But Im enthusiastic about new research organizations that specialize in funding young scientists.

Another matter worth investigating is that other countries dont share the gerontocracy problem across disciplines. In the U.K., for example, the public is getting older, but its leaders arent. I think we should be more open to asking hard questions, such as If the Democratic Party is the preference of Americas young people, why are so few young people represented in its leadership? and How do we balance a respect for the elderly with a scientific approach to evaluating the cognitive state of our oldest political and corporate leaders? In the end, this is about nothing less than how an aging country learns to grow up wisely.

Want to discuss more? Join me for Office Hours August 16 at 1 p.m. ET. This month, Ill discuss whether weve missed our chance to tackle climate change with my colleague Robinson Meyer. Ill continue to hold office hours on the second Tuesday of each month. Register here and reply to this email with your questions about progress or the abundance agenda. If you cant attend you can watch a recording any time on The Atlantics YouTube channel.

Original post:
How Pop Culture, Politics, Science, and Business Got So Old - The Atlantic

One of the consequences of writing a syndicated column on politics and public policy for more than a quarter of a century is that I am constantly told what I think and why I think it.

You may find this consequence perplexing. Isnt my job here to tell readers what I think and why I think it? Sure. But most readers arent passive recipients of information. They listen critically and answer back, even if only in their heads. Some go further. They write me, call me or send letters or comments to the newspapers that run my column.

A common theme in such correspondence, especially over the last several years, is that I dont mean what I say. Some accuse me of parroting someone elses beliefs instead of my own. Others ascribe opinions or goals to me that I dont have or would even find abhorrent.

I appreciate the entertainment value of armchair psychiatry, conspiracy theories, and political sophistry as much as the next person. But just in case there is any doubt, let me restate some basic facts about my beliefs, my work, and this column.

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First, I write whatever I like, about whatever I like. Naturally, the editors who run my column correct spelling and grammatical errors. They edit for length. And they ask for clarifications when I explain myself poorly or cite a statistic they find confusing or improbable. But thats it. No one is in a position to approve or disapprove of my work.

Second, I believe what I say I believe. Although my views have shifted over the decades on a few issues, in response to changing circumstances or different facts presented to me, my core beliefs are the same ones I espoused in my high school newspaper, the student magazine I founded in college, and the syndicated column I began writing for North Carolina newspapers in the summer of 1986.

I believe in personal freedom and in the personal responsibility that inevitably comes with it. I think human beings tend to be wealthier, healthier, and happier to the extent they are freer. I also think human beings have an inherent right to be free, simply because they are human beings. That is, I believe in and employ both consequentialist arguments (freedom is good for you) and natural-rights arguments (freedom is your birthright).

To say that freedom is my highest political value is not to say that I dismiss others. Nor does it mean that I oppose all government actions that inhibit freedom. Indeed, I recognize that government actions are inherently coercive. Im not an anarchist. In fact, I dont think anarchy is a coherent idea. Human beings crave freedom but are also, by nature, often tempted to be disagreeable, shortsighted, and violent. Thats just basic psychology and another inescapable fact of history.

So I believe government should (and always will) exist to protect individual rights and to finance certain core services that, because of collective-action problems, will not be adequately provided through purely voluntary means. At the state and local level, those services include public safety and health, education, and some infrastructure.

These views were traditionally described as liberalism in the tradition of John Locke, Adam Smith, and their intellectual progeny until the early 20th century. Thats when left-wing progressives successfully redefined the term. So today, my philosophy is considered conservative, libertarian, fusionist, or perhaps conservatarian, which is an unlovely but reasonably accurate term.

I firmly believe that maximizing freedom produces large, persistent social benefits. A steady stream of empirical research informs my belief. In recent years, academic studies have confirmed that economic freedom correlates with faster economic growth, higher living standards, more investment in developing countries, greater longevity, a freer press, greater public trust, and higher average levels of happiness.

I and others who espouse the virtues of smaller government and greater freedom may be mistaken. But our beliefs derive from logic and experience. Please structure your rebuttals accordingly, and thanks for reading.

John Hood is a John Locke Foundation board member. His latest books, Mountain Folk and Forest Folk, combine epic fantasy with early American history (FolkloreCycle.com). Follow Hood on Twitter @JohnHoodNC

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John Hood: How to read this column | Columnists | journalnow.com - Winston-Salem Journal

While there are generally three schools of thought around this topic, it's interesting to explore the idea that our life spans could be unlimited if we care for our bodies in a certain way. At the moment, there's limited data to depict the likelihood of living past the age of 110, but one study has found that your chance of death actually plateaus at that age. Patrick explains the researchers used "extreme value theory," which is a field of statistics focused on predicting incredibly rare events. According to the research, while your chances of dying (obviously) increase with age, they level out at 110, and your odds of living to the next year lands at about 47%. She likens this to flipping a coin.

"In the other study, researchers investigated whether people will likely surpass 120 years of age (the current records), or even older, in the next century," Patrick explains in her newsletter. "Their findings suggested that the current records will likely be broken in the next 80 years or so, but it's unlikely that anyone will live beyond 135 years."

Interestingly, in 110- to 115-year-olds, there were no statistically significant differences in sex, genetics, diet, and general lifestyle. Of course, the sample size of these findings is quite small (566 life spans were studied and only nine lived to the age of 115), so only time will really tell if we can continue to increase the average age.

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How Long Is The Human Lifespan? Here's What Studies Have Found | mindbodygreen - mindbodygreen

Consider this statistic about human longevity: 50% of 5-year-olds who live in the richest economies on the planetplaces like the United States or France or Japancan now expect to live to the ripe old age of 100.

Welcome to the era of the super-agers. Life expectancy in much of the developed world more than doubled last century. And, thanks to advances in medicine, public education and sanitation, human longevity will continue to blossom in the years ahead, demographers say, extending life for many of us into the triple-digit range. Maybe we wont need billionaires like Jeff Bezos, Peter Thiel or Larry Page to fund some kind offountain of youth breakthroughafter all.

The glass-half-empty take is a bit harder to swallow. People are regularly living 30 and 40 years beyond their retirement age at a time when birth rates are in decline. These defining and conflicting demographic trends lead to all kinds of concerns that privately- and nationally-funded pension systems, created in an age when life expectancy wasnt quite so rosy, will fall short of their promise to fully support us once we say goodbye to our careers. The age-old challenge of keeping publicly-funded retirement plans solvent boils down to the question: can society maintain a sufficient population of working-aged people to pay into a national pension plan, thus funding the monthly payouts to retirees?

In May,a surveyof pension fund managers from the United Kingdom bore out fears of a looming demographic time bomb tick, tick, ticking. Asked about the biggest threat to their funds performance, the fund managers No. 1 response was inflation. The second most cited concern? Longevity, or people living too long.

This kind of Malthusian thinking is corrosively misplaced, a growing contingent of retirement experts, economists, and researchers say. With people living longer and healthier lives, they counter, business leaders should nurture this phenomenon, and harness its potentialfor both the demographic on the brink of retirement and their younger cohorts.

This crisis mindset assumes that people will agein the future as they did in the past, that financing 100-year lives is a challenge made insurmountable by the projected insolvency of the Social Security trust fund, and that additional mechanisms for saving, investing, and supplementing income are beyond reach, argued an influential white paper published last year by theStanford Center on Longevity, aresearch collectivefounded by Stanford University professor Laura Carstensen, one of the foremost experts in aging and longevity.This static view of what it means to age distorts our perspectives about longevity in the future, and overlooks the opportunity to change the trajectory of aging and associated costs, by starting now to redesign institutions, practices, and norms so that they align with todays reality, rather than last centurys.

In thebefore times, back in 2018, the Stanford Center on Longevity started to work on this redesign challenge. For example, it developed what it calls a new map of life, a kind of framework for policymakers that sought to advance the longevity discussion towards the many benefits the white-haired population can bring to businesses and society at large. In place of the outdated assumption that older adults drag down productivity and drain societal resources, we take a forward-facing perspective on the economic potential of a more age-diverse population in which older adults contribute inincreasingly significant and measurable ways to thesocial good and to GDP.

Out is talk of the above-60 crowd as a burden on the public purse. In is a newfound understanding and appreciation for whats being called thelongevity economy.

In May, in Davos, Switzerland, the World Economic Forum convened a series of high-level discussions about how to harness and capitalize on the longevity economy. The focus was two-pronged: how to support the financial, physical, and mental wellbeing of the soon-to-retire crowd, and how to better leverage their experience and career wisdom for the benefit of their younger colleagues. It was a really outstanding discussion, Haleh Nazeri from the World Economic Forum, who was part of the team organizing the longevity track, toldFortune.

Nazeri, whose work at WEF focuses on longevity and financial wellbeing, has been talking with business leaders and policymakers for the years about the need to rethink retirement systems. In an era of super agers, she says, corporations and governments need to adapt. For starters, the one-size-fits-all retirement plans of the past, where money is saved up to be spent in the later years of life, is neither feasible nor practical, shesargued.

Instead, she offers a few ways todays leaders should be thinking about getting the most out of aging workforces, and how to support employees transition to a new life once their careers wind down.

For starters, employers should accommodate workers by building in so-called on-ramps and off-ramps throughout their working life. Its kind of an elegant way to say people might need breaks throughout their careers, she says. An employee may need a career hiatus to start a family, for example, or care for an elderly or sick loved one, or take a sabbatical to pursue an area of interest outside of work.

These off-ramps should be supported, and even encouraged by managers, she argues. And, when its time for a worker to come back, an on-ramp is needed to smooth out the transition. Many companies are beginning to see the need to allow for career pauses, which may ultimately push the standard retirement age for some workers well into their late 60s and beyond. Prudential Singapore, for example, recently scrapped its retirement age entirely to create a more age-friendly workplace and build in some flexibility for staffers who want to pad their pension nest-egg.

Plus, giving workers the space they need in their pre-retirement years could prove fruitful down the road. Nazeri gives the example of the worker who decides to take a sabbatical mid-career. The experience, she notes, may prove life-changing, opening up opportunities for the worker after she retires.

When it comes to retirement, some employees may find the prospect of leaving a secure career a major jolt. Thats why an organizational plan is needed. One suggestion that came up repeatedly at Davos was the need for phased retirements, Nazeri said. In a phased retirement program, senior staffers, those at or nearing the end of their careers, would begin transitioning to two- or three-day work weeks, she adds, instead of just retiring one dayyou hit 65, and that persons gone.

Executed well, the phased retirement would be minimally disruptiveto the employee, and to her colleagues. It would allow the company to continue to reap the social benefitsthink experienced workers mentoring and on-ramping younger staffof an inter-generational workforce. At the same time, the expectant retiree could maintain both a steady paycheck and hold onto that close bond she has with co-workers. Community is one of the more important thingsas people retire and leave their jobs, they lose that [sense of community], you know, and it can lead to all sorts of things like depression in older age, Nazeri notes.

Nazeri fully acknowledges that COVID has probably inalterably messed with office life and the workplace atmosphere we used to share with our colleagues. But she also sees how the new way of working could make phased retirement scheduling more palatable to managers. After all, the onset of hybrid working, where some of us come into the office two or three days a week, is not an unusual decision anymore, she says.

The practice of phased retirement is gaining traction with companies, and their employees. Earlier this year, the consultancy Mercer LLC, which is working with WEF on the retirement conundrum, found that nearly two in five (38%) of the firms it surveyed offered some kind of phased retirement package for employees.

The longevity discussion is also pushing companies and policymakers to confront the problem of inadequate pensions, particularly in an age of runaway inflation.

In the same survey, Mercer found that 84% of the employees it polled said they plan to work as long as they can for fear their pension is too meager to support them. This problem is particularly acute with women who continue to earn less than men, and therefore have accrued less savings. The focus on earnings shortcomings has given rise to the discussion about living pensions. Like a living wage, a pension should be designed equitably so that workers can actually live off of it.

One organization pushing companies to make employee compensation more generous and fairer is the British non-profit the Living Wage Foundation. Each November, it calculates a real living wage, one based on the cost of living. It challenges employers to adjust salaries according to this annual calculation. So far, scores of companies have signed on to the pledge, including KPMG, Aviva, Burberry, Nestl and Ikea.

One participant, Aviva, believes the living wage approach could be applied to pensions as well. The idea would be to adjust retirees payouts annually so as to ensure their real pension doesnt get clobbered by inflation.

Aviva calls the living pension a game-changer, particularly for women and low-income earners.

Nazeri, for one, applauds the recent flow of ideas to tackle the pension puzzle. Solving it starts with seeing pensioners and the soon-to-retire crowd as an asset to an organization, and to society.

I feel like we need to discuss this even more, she says, because its going to impact the entire world.

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Employees are livingand workinglonger. CEOs are introducing initiatives like phased retirements to harness the longevity economy - Fortune

Everybody gets older, although not everyone ages in the same way. For many people, late life includes a deterioration of health brought on by age-related disease. Yet there are also people who retain a more youthful vigor, and around the world, women typically live longer than men. Why is that? In this episode, Steven Strogatz speaks with Judith Campisi and Dena Dubal, two biomedical researchers who study the causes and outcomes of aging to understand how it works and what scientists know about postponing or even reversing the aging process.

Listen on Apple Podcasts, Spotify, Google Podcasts, Stitcher, TuneIn or your favorite podcasting app, or you can stream it from Quanta.

Steven Strogatz (00:03): Im Steve Strogatz, and this is The Joy of Why podcast from Quanta Magazine that takes you into some of the biggest unanswered questions in science and math today. In this episode, were going to be talking about aging. Why exactly do we age? Whats happening at the cellular level as our bodies get older?

(00:22) Scientists are still chasing many of the answers, but there have been some important advances in understanding the distinctive changes we call aging. Someday, that progress might not only help us live longer, but live better too. After all, living many years may not be much of a bargain if it means suffering from diseases like Alzheimers or Parkinsons. Well ask what role do our genes play in aging? And why do women tend to live longer than men on average? And also, what is research finding out about the ways we might slow down the process of aging?

(01:00) Later in this episode, well be hearing from Dr. Dena Dubal, associate professor in the department of neurology at the Weill Institute for Neurosciences at the University of California, San Francisco. But first, joining me now is Dr. Judith Campisi, a biochemist and cell biologist and professor at the Buck Institute for Research on Aging. Her lab there focuses on cellular senescence, a concept that well be unpacking very shortly. She is co-editor in chief of the Aging journal. Judy, thanks so much for joining us today.

Judith Campisi (01:34): My pleasure.

Strogatz (01:35): Im very excited to be talking to you about this. Well, of course, all of us are getting older, and we all feel it. It raises so many questions, though, like why is it happening? Is it something that nature is doing on purpose? Is it that our bodies are kind of wearing out like an old machine? Or how should we think about it?

Campisi (01:54): I think the way we have to think about it is in the context of evolution. If you think about humans, our lifespan, over the course of our evolution, aging never happened. There was no Parkinsons disease, no Alzheimers disease, there was no cancer. Everybody was dead by the age of 40 or 45. So evolution put into place ways of keeping young, reproductively fit organisms healthy for only a few decades, certainly not for the larger number of decades that were living through.

(02:35) Now, many of the processes that happen during aging really happen as a consequence of the declining force of natural selection. That is, there was no natural selection for these diseases. The process we study, cellular senescence, its now clear and certainly in mouse models that this process, the cellular process, drives a large number of age-related diseases, everything from macular degeneration, to Parkinsons disease, cardiovascular disease, and even late-life cancer, but it evolved to protect young organisms from cancer.

(03:19) So we certainly dont want to stop it when were young. It also helps fine-tune certain structures during embryogenesis. And it initiates labor in women in the placenta. So these are the things that evolution is selecting for. And this is why we have to be careful in how we intervene. And thats true for almost everything that happens with age. Evolution didnt try to make us old. Evolution tried to make us young and healthy. And sometimes that came at a cost.

Strogatz (03:56): Its a fascinating perspective, actually, that the things that are healthy for us when were young and that would be selected by evolution can have this inadvertent consequence. That as weve been able to extend lifespan I suppose through better diet or medicine, all kinds of things that now what used to help us can hurt us.

Campisi (04:15): Yes, this idea that whats good for you when youre young, can be bad for you when youre old. It was proposed in the 1950s by a guy named George Williams, an evolutionary biologist named George Williams. There was no molecular data at that time, you know. No genomes had been sequenced. He pointed out evolution never had to fine-tune the prostate. If you dont have a good prostate, you dont have good babies. You dont make good babies. On the other hand, almost inevitably with age, over the age of, say, 50 or so, the prostate begins to enlarge and of course it becomes a possibility of developing into cancer. Yet that didnt happen for most of our evolutionary history.

Strogatz (05:02): Wow. So lets go into cells because this its so rich and wonderful what you and your students and colleagues have been discovering at the cellular level. So could you please define what it means for a cell to be senescent?

Campisi (05:17): It is a state that the cell enters, in which it adopts three new traits. One of them is it gives up almost forever, almost forever, the ability to divide. It will tend to resist dying. And most important, it tends to secrete a lot of molecules that can have effects on neighboring cells, and also in the circulation. Not that many cells have been studied when they become senescent. And almost everything else we know about senescence is slowly changing as we learn more and more about different cell types and different ways that cells enter senescence.

(06:00) Okay, so they stopped dividing. And that makes sense that that would prevent cancer. The other thing is they become relatively resistant to cell death. That is they stick around. And this could explain why they increase with age, and they do. Many people now have looked in many, many vertebrate tissues. And it just seems that the older the tissue, the more senescent cells are present.

(06:29) The caveat to that statement is, there are still very few of them even in very old and very diseased tissue. A few percent at the most. So why do people think this has anything to do with aging? That has to do with the third thing that happens when cells become senescent is they begin to secrete a large number of molecules that have biological activity outside the cell. And that means that those senescent cells can call immune cells to the site where they are, it can cause neighboring cells to fail to function. And it basically causes a situation that is classically termed chronic inflammation. You know, and of course, chronic inflammation is also a great risk for developing age-related cancer. Not so much childhood cancers, but age-related cancers.

Strogatz (07:26): So a certain small subset of cells that stopped dividing hang around for a long time, dont dont die, and yet secrete molecules that call immune cells or other parts of the immune system to come. And what I mean, are they signaling come and kill me? Or whats going on? Why are they, what are they secreting for?

Campisi (07:50): Yeah, so theyre secreting a large number of molecules. So some of them are growth factors. And we reported some time ago, that at least on a mouse, if you make a wound, like a skin wound just a little punch biopsy on the back of the mouse at the site of that wound, senescent cells form within a few days, and they secrete growth factors that help the wound heal.

(08:17) This is why evolution selected for this phenotype. Its not all bad. On the other hand, if you have a pre-cancerous cell nearby, and those growth factors are now being secreted, and this cancer cell sees them, its possible that that cancer cell will wake up and start to form a tumor. So again, good for you when youre young, bad for you when youre old.

Strogatz (08:44): Well, let me ask some basics while were talking about senescent cells, because I think there are some things Im curious about. For instance, should I think of them as having started out like any other kind of cell and something set them on a pathway to become senescent? Or are we born with them? Or whats, whats the right way to think about this?

Campisi (09:04): I think where the field is right now is were beginning to realize that all senescent cells are not equal. And then the question is, why would what starts out as a normal cell so youre right, you start out with a normal cell. What would make it enter this strange state where it doesnt divide? And its got all these molecules it has to make and secrete. And the answer is, the kinds of stresses that we tend to associate with both cancer and aging. So for example, anything that damages the genome or even damages what we now call the epigenome. The way genes are organized within the nucleus, anything that damages that has the potential to drive a cell into this senescent state.

(09:51) On the other hand, there are also stresses that we dont think about as normally associate certainly, not associated with cancer. But things, for example, like advanced glycation end products, the chemical reactions that take place when glucose levels are too high. And so this is a big problem with people who have diabetes or pre-diabetic conditions. So those, those chemicals can also cause the cell to become senescent. So its more appropriate to call it a stress response, except not all stresses result in senescence.

Strogatz (10:30): Let us, if we could, talk about the mouse experiments that you and your, your group have done really pioneering experiments where youve used the technique in molecular biology of transgenic mice. Maybe first, you should tell us what they are, and then how you use them as a kind of testbed for how to get rid of bad senescent cells.

Campisi (10:49): So right now in biology, its pretty straightforward and easy to insert DNA into the genome of a mouse, and then have that mouse develop into a full-blown adult mouse and have that adult mouse make babies. And so the mouse that we made, this trans. So thats called a transgene, the transgenic mouse we made, carried a piece of DNA that had a foreign protein made when cells become senescent. And that foreign protein had three parts. A molecule that was what we call luminescent, meaning we could image the cells in a living animal. It had a fluorescent protein, which meant that we could sort senescent cells from the tissues of that mouse. But most importantly, it had a killer gene, a gene that would normally be totally benign. But if you feed a drug, which is also very benign, that drug and the presence of that foreign gene will cause senescent cells to die.

(12:01) So we made this mouse quite a while ago. And weve shared it with dozens and dozens of academic labs that are studying different diseases of aging: Alzheimers disease, Parkinsons disease, cardiovascular disease, age-related cancers, osteoporosis, osteoarthritis, et cetera. And the results are just astounding.

(12:27) If you eliminate senescent cells, it is possible to do one of three things to an age-related pathology: You either make it less severe, or you postpone its onset, or and this is, of course, the one we all love in a few cases, you can even reverse that pathology.

Strogatz (12:49): Oh wow.

Campisi: I know. Thats true for osteoarthritis so far. And so this has now sort of given meat to the idea that developing drugs that can do what our transgenes can do. Its too late for any adult to get their transgenes. But if you have an unborn baby, it may be possible.

Strogatz (13:09): Oh, I see where youre going with that. I mean, thats, of course, thats a big can of worms for us, isnt it to think that, you know

Campisi (13:15): I know, its too political. Its already been done.

Strogatz (13:17): Oh, really?

Campisi (13:19): Well, its been done. Its been done in China. Right?

Strogatz (13:22): Youre saying that fetuses or before fetuses

Campisi (13:25): Thats correct. Was engineered. Yeah. I dont know the guy who did it, the Chinese guy who did it was condemned by the community because there were not enough controls there. No oversight, et cetera, et cetera. But its possible. Theres no intellectual reason why we cant make transgenic people. And my guess is, its not just China.

Strogatz (13:45): Okay, in terms of what was actually we know that youve done in you and the other people doing transgenic mice, if I just make sure I got that. You said there were three parts to the transgene, two of which it sounds like were for detecting. So theres the luminescent and the fluorescent part. But the, the killer part is the part that is playing the role of in the future drugs, I suppose, that could kill off the bad senescent cells. You had this genetic mechanism

Campisi (13:46): Thats exactly right. So the drug that we use to kill senescent cells in the mouse would not work in humans because humans are not transgenic. But the idea would be now to develop new drugs. And they are being developed. There, there are already some that are being used in mice, and even a few in early-stage clinical trials in people with the idea that they would mimic what our transgene can do in the presence of this otherwise benign drug.

Strogatz (14:13): And so the punchline here is that if this really comes to pass, this gives us hope for, as you said, postponing, ameliorating or in some cases maybe again, were dreaming, but its like theres science behind this or possibly reversing some of these many age-related diseases. Just that you told us about. Yes. Wow.

Campisi (15:01): Youll die on the tennis court at 110. But youll be winning.

Strogatz (15:06): Thank you very much, Judy. This has been just a delightful conversation, my pleasure.

Announcer (15:14): Explore more science mysteries in the Quanta Magazine book Alice and Bob Meet the Ball of Fire, published by The MIT Press. Available now at Amazon.com, Barnesandnoble.com or your local bookstore. Also, make sure to tell your friends about The Joy of Why podcast and give us a positive review or follow where you listen. It helps people find this podcast.

Strogatz (15:39): Why we age and what happens to our bodies as we age are two of the biggest mysteries about aging. Another mystery has to do with sex differences. Women tend to live longer than men. Its often said that they live three to five years longer. But really, if you look at the global statistics, you see that in some places, women live more than 10 years longer. So what is it about being female that makes women more resilient? The body of a 70-year-old woman may be younger than her 70 years biologically when compared to that of a 70-year-old man. Researchers on aging say that an epigenetic clock runs differently for each.

(16:19) If we can understand why a womans brain might also age differently than a mans, we might be able to develop therapies to help everyone. Research into this question gets us into proteins and sex chromosomes and hormones. The goal is to understand all of this better. Can we slow down the aging process somehow?

(16:39) Joining me now to discuss all this is Dr. Dena Dubal. Shes an associate professor of neurology at the University of California, San Franciscos Weill Institute for Neurosciences. Her lab studies female longevity and the aging brain. What makes it resilient against cognitive decline? Dr. Dubal is also an investigator with the Simons Collaboration on Plasticity and the Aging Brain. Dena, thank you so much for joining us today.

Dena Dubal (17:06): My pleasure. Thank you for inviting me.

Strogatz (17:08): Well, Im really pumped up by this. You know, I think in my own family about how sharp some of the women were in their 90s, even. I recently had an aunt who just passed away just shy of her 100th birthday. She had smoked her whole life. But she was sharp. And I dont know how she could have managed to live so long. The men were all gone, the husbands had all died.

Dubal (17:32): Yeah, I noticed something similar in my family of origin, when I was very young, and that is that women live longer than men. And every summer growing up, my parents would take me back to India, their country of origin. Theyre immigrants from India. And we would spend time in a very small village in western Gujarat. And it was really remarkable that the elderly were, were really mostly women. And I had a great-grandmother, whose name was Rumba, who was just a remarkable woman, not educated, but really smart. And she lived almost to her 90s. And her husband, my great grandfather, despite being robust, tall, handsome and also very smart, he died in his early 40s. And so her lifespan was nearly double that of his. And this was seen really throughout my extended family, that the women live longer than the men and I always wondered why that was.

Strogatz (18:41): I mean, Im sure that many of our listeners are thinking the same thing. Its a pretty commonplace experience that the, the women outlive the men. Of course, its not universal. There are exceptions for all kinds of reasons, but, but its just an amazing general trend.

Dubal (18:55): So in every society that records mortality across the world, women live longer than men. From Sierra Leone, where lifespan is lower, to Japan and Sweden, where lifespan is much longer. But heres a really interesting piece of information: When we look historically across multiple countries and societies, at times of extreme mortality, like famine and like epidemics, the girls will live longer than the boys and the women will live longer than the men.

(19:34) And this, this really suggests to us that there is a biologic underpinning for female longevity, because even when there is very high and equal stress in the environment with very high mortality, the girls are outliving the boys and the women are outliving the men. Theres some very, very sad and really remarkable times that, that demonstrate this including the Irish famine and many, many other examples in our world history.

Strogatz (20:04): Its, its really fascinating to think that its somehow so intrinsic, that theres something you know, youve mentioned the cultural aspects, but it does feel like theres something purely biological also going on. And I wonder if we could get into that. I mean, is there something happening in the body itself that could account for these differences?

Dubal (20:26): There can be, really I would say, four main reasons. If we think about this, biologically, why there could be sex differences and human longevity. One has to do with sex chromosomes, our genetics, our genetic code, and every single one of our cells in our bodies. And that is that female mammals and certainly female human mammals have two X chromosomes in every cell. One of them is inactivated during development, but there are two X chromosomes, and that is the sex chromosome complement of women and girls. In contrast, boys and men have one X and one Y.

(21:12) And so here already at the outset, there is a very clear and striking difference in our genetics. And so with this difference, and XX in females compared to XY in males, there, there arises for biologic reasons, for sex differences in longevity. One is that in males, theres a presence of a Y. And it is thought, although not experimentally shown, that maybe there are toxic effects or deleterious effects of the presence of a Y chromosome.

Strogatz (21:48): Wow, what an idea. Well, why do living things get old at all? Why dont we live forever? What causes aging in the first place?

Dubal (21:56): Thats a very simple yet philosophical question. I would say that aging is what happens with the passage of time to the biology of cells. There is a change in biologic functions that leads to dysfunction and vulnerability to diseases. One major cause is genetic instability. So over time, our genetic code becomes more unstable. Some mutations will occur. Parts of our genes kind of jump around those are called transposons and disrupt other parts of our genetic code. There are changes that occur epigenetic, that means on top of our genes that ultimately change the way that our cells express themselves. And that becomes dysregulated and more dysfunctional over time with aging.

Strogatz (22:54): All right, well, so theres, the story of why we age then is a very multi-faceted one, apparently.

Dubal (23:01): Yeah, yeah, and the loss of what we call homeostasis. But really, what that is, is housekeeping of proteins. How theyre turned over, how theyre modified, how theyre folded, what is done with the proteins in our cells. And the housekeeping of these proteins declines with aging. And so then theres this buildup of essentially gunk, of like clutter, that really jams up cellular processes and contributes to aging as well. Mitochondria are the powerhouses of our cells, and they have more dysfunction with aging.

(23:40) This brings us back to another possible biologic reason for female longevity, it brings me to something called the mothers curse. So all the mitochondria in all of your cells, Steve, and all of mine, are inherited from our mothers. So in the process of, of cellular division and the creation of a zygote, mothers pass on their mitochondria, not fathers. And so this, this becomes really important because mitochondria can only undergo evolution in a female body. Males will never pass their mitochondria on.

(24:24) And so at the end of the day, what that predicts is that mitochondrial function is more evolved to female physiology, when compared to male physiology. And this may make a difference with aging when things begin to go awry. The female cells may be more fit because their mitochondria are more evolved to the female cells compared to male cells. For males, that would be a mothers curse.

Strogatz (24:50): And then a mothers blessing for females, maybe. Interesting. This is this is an interesting thing. Wow. So that gives me a very good big picture about whats happening. So living longer, though, is just one aspect of what well be discussing here. Theres also the issue of living better, right? In terms of not in the case of people, not experiencing the cognitive decline that we or reducing that, that we all associate with getting older.

Dubal (25:18): Yeah. So, lifespan is one thing, right? How, how long does one live? And right now the oldest recorded person in history has lived to approximately 122 years old. But then health span is really a measure of how many healthy years of life is one living. Thats what we really aspire to, is really good healthy health span, where we are not suffering from cancers, cardiovascular disease, neurodegenerative diseases, like Alzheimers, cognitive decline and more that happens with aging.

(25:58) So with a very good health span, one lives a healthy life without these chronic debilitating conditions until, lets say, 100 and then one dies peacefully in ones sleep from pneumonia, lets say. But that is health span. Its really life lived without diseases. And, you know, the reason that we are so interested in lifespan is that the things that help us to live longer tend to help us to live better.

(26:32) So if we can understand the molecules that work together to conspire toward longevity, we can harvest those molecules to help fight disease. And thats why were so interested in, Wow, why is it that women live longer than men? Is there some biology of aging that can be discovered, learned and then harvested toward better health span in males and females?

Strogatz (27:02): Well, let us start getting into that, then. I mean, I suppose our common sense would say that its got to be about sex hormones. That we associate testosterone with men, estrogen with women. Is it estrogen thats the secret here that, that thats somehow protective? Or lets, lets start with that. Is it, is this a story of estrogen?

Dubal (27:24): Yeah, its a golden question. So this brings me to the fourth biologic reason for sex differences in longevity. One was, could it be the presence of a Y that increases mortality? Is it an extra X in females that extends lifespan? Is it a mothers curse of mitochondrial inheritance from mothers only that works against males? And fourth, what about sex hormones? Could it be that testosterone is decreasing lifespan in males and estrogen is increasing it in females?

(27:58) I think this is a really important possibility and considering sex differences in biology and in longevity. And we have some very interesting clues from natural human experiments and experiments in animals.

(28:16) There is some support that removing testosterone prolongs life. The Korean Chosun dynasty had a population of Korean eunuchs, that were castrated. They were useful and respected members of the dynasty and of the imperial court. And they lived a very long life, a significantly longer life than men of the same socio-economic status that lived at the same time on average, 15 years longer.

Strogatz (28:49): This is amazing.

Dubal (28:51): Right?

Strogatz (28:52): Wow!

Dubal (28:52): It suggests that decreasing testosterone prolongs life. And we do see this, actually. There have been animal studies in which sheep are castrated and will live longer compared to those that are not. And some very robust studies in dogs. Of course, we spay our dogs and castrated male dogs will live longer than non-castrated male dogs.

(29:16): But, Steve, I have to tell you that this question that you asked was burning me for many, many years. Could it be the hormones that contribute to female longevity? Is it estrogen, or could it be sex chromosomes that contribute to longevity? And to that point, we did a really neat experiment to be able to dissect out those two causes, and Id love to explain it if this is a good time.

Strogatz (29:42): Its perfect and, and I like that you, you describe it as neat because I read in reading about it to prepare for our conversation. I thought this was such an elegant and you know, this is like primo science. This is the scientific method, to ask this tricky question and find a way to get a good approximation to an answer to it.

Dubal (30:04): It was a really exciting experiment to do. And it mattered not what the results were, we were to follow the science and the science would tell us something about the cause of sex differences in longevity.

(30:18) And so to be able to dissect out whether female longevity was driven by hormones, or by sex chromosomes, we used a really elegant, as you said, animal model, called the FCG model, the four core genotypes model. And in these mice, theres, theres a genetic manipulation, theres a genetic engineering thats taken place. And that is on the Y chromosome, there is this SRY, or a testis-determining factor, theres a gene that causes male differentiation and the production of testes and testosterone.

(30:58) So in this model, SRY is taken off of the Y chromosome and added to any other autosomes, the non-sex chromosomes. And what this allows is the inheritance of this testicular determining factor, the SRY, the inheritance of it by males that are XY or by females that are XX. So at the end of the day, this genetic engineering enables the creation of mice that have four sexes: XX mice with ovaries, that is the typical female biologic genotype and phenotype. XX mice that have developed as male with testes. And thats again, because they inherited the testicular determining factor SRY and they have differentiated as males and they, they cannot be distinguished from other male mice, except that theyre XX. So they have testes, they have male reproductive behaviors, they ejaculate. They fight in their cages. They are male mice, except theyre XX.

Strogatz (32:10): Hmm. So Ive got it. I want to make sure everyone listening has got it because its so incredible this way of doing things that the, you can make. I mean, let me put it crudely I think its approximately right phenotypically, on the outside, they look like males but inside, in terms of their chromosomes, they look like females.

Dubal (32:29): Thats right. Thats right. And then we do the same in males, in that we produce XY males that lack the testis determining factor and have developed by default as females that is, that they are indistinguishable from other female mice. They have ovaries, they have a uterus, they cycle, they have female reproductive behaviors, they are female mice, except their genetics are XY. And then we have the typical male, that is XY male that has developed a male phenotype.

(33:08) So this model produces four sex genotypes with males and females, XX and XY that developed with either ovaries or testes. And this allows us to really track which mice will live longer. Is it the mice that have ovaries regardless of being XX or XY? Or is it the mice that are XX, that have female genetics, regardless of growing up with ovaries or testes?

Strogatz (33:37): Before you reveal the answer? Let me ask the question a different way because I want everyone to mull this question over in their head, and guess what the answer is. So the question is, youve created this thing thats a little hard to wrap our minds around, but I think weve got it. These four sexes, a traditional male, a traditional female, a male genetically, but I dont know which one you call the male. Do you call you call, you refer to male as anything thats XY, is that right?

Dubal (34:07): I do. But its, its a matter of taste and, and style.

Strogatz (34:11): Okay, but so its an, its an organism thats XY but has ovaries, yes. Or you can have an organism thats X. Its not an organ. Its a mouse that has XX, but has testes.

Dubal (34:24): Its, its sudoku. Its like this is scientific sudoku.

Strogatz (34:30): Thats great.

Dubal (34:30): Yeah, we actually didnt have a specific hypothesis, we were going to follow the science. And what we found very clearly, is that the mice with two X chromosomes lived longer than those that were XY. So the XX mice, regardless of growing up with ovaries and having lots of estrogen, or regardless of having testes and lots of testosterone, it was the XX mice that lived longer compared to the XY. So this was a decisive genetic experiment that showed us really for the first time that sex chromosomes contribute to female longevity.

(35:14) Now, there was more that the experiment taught us too. The mice that lived the longest of all the groups, or the mice that had ovaries combined with the XX chromosomes, those lived to maximal longest lifespan, suggesting that the hormones produced by the ovaries, that ovaries and the hormones also contribute to female longevity. And that maybe testosterone is deleterious. So the answer was, the main statistical effect was that sex chromosomes contribute to female longevity. However, the hormones did have an effect in there as well.

Strogatz (35:56): So of the four sexes that we could choose from in this sudoku that you created, the traditional female, if I can keep referring to it as that, seems to be the winner?

Dubal (35:56): In living the longest. Yes.

Strogatz (36:12): What about the worst? What about the one living the shortest is what I would guess?

Dubal (36:16): The XY with testes? The XX mice, whether they grew up with ovaries or testes, lived longer than the XY mice that grew up with ovaries or testes. XX mice lived about 15 to 20% longer than XY mice.

Strogatz (36:33): Thats an enormous difference. It really, I mean, I assume by any statistical measure was considered significant. Your statisticians must have said, is that right?

Dubal (36:41): Absolutely. Very, very clearly significant, a very clear sex chromosome effect.

Strogatz (36:47): Well, thank you on that very inspiring and thoughtful note, Dena. You know, this was a really just an outstanding discussion. Thanks so much for joining us today.

Dubal (36:55): My pleasure.

Announcer (36:58): Wants to know whats happening at the frontiers of math, physics, computer science and biology? Get entangled with Quanta Magazine, an editorially independent publication supported by the Simons Foundation. Our mission is to illuminate basic science and math research through public service journalism. Visit us at quantamagazine.org.

Steve Strogatz (37:22): The Joy of Why is a podcast from Quanta Magazine, an editorially independent publication supported by the Simons Foundation. Funding decisions by the Simons Foundation have no influence on the selection of topics, guests, or other editorial decisions in this podcast or in Quanta Magazine. The Joy of Why is produced by Susan Valot and Polly Stryker. Our editors are John Rennie and Thomas Lin, with support by Matt Carlstrom, Annie Melchor and Leila Sloman. Our theme music was composed by Richie Johnson. Our logo is by Jackie King, and artwork for the episodes is by Michael Driver and Samuel Velasco. Im your host, Steve Strogatz. If you have any questions or comments for us, please email us at quanta@simonsfoundation.org. Thanks for listening.

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Why Do We Get Old, and Can Aging Be Reversed? - Quanta Magazine