What the Latest Research Says about Adding Healthy Years to Your Life

Matt Fuchs wrote . . . . . . . . .

Death comes for us all. But recent research points to interventions in diet, exercise and mental outlook that could slow down aging and age-related diseases – without risky biohacks such as unproven gene therapies. A multidisciplinary approach involving these evidence-based strategies “could get it all right,” said Valter Longo, a biochemist who runs the Longevity Institute at the University of Southern California’s Leonard Davis School of Gerontology.

There’s a debate, however, about how much we can increase our longevity. All humans share 99.9 percent of their genes. This explains why even “super-agers,” born with tiny genetic differences that promote longevity, almost never surpass 110. (Jeanne Louise Calment of France was an outlier, living until the age of 122, the current record.) Some animals make it well beyond that mark, according to Jan Vijg, a molecular geneticist at the Albert Einstein College of Medicine. Scientists know just one way for humans to live 170 years like a giant tortoise: become a giant tortoise.

Some experts do find it likely that someone will set a record for our species by the end of this century. Statisticians have observed a “mortality plateau” for very old people; although the chance of dying in a given year goes up with age, the odds seem to stop increasing after 105. Beyond this plateau, it’s basically a coin toss every year: Heads you’ll see your next birthday, tails you won’t.

But the mortality plateau is often debated. Even if it’s true that the risk of death levels off, this won’t necessarily result in super-agers living longer than before. Susan Alberts, a Duke University primatologist, published a paper that compared the human rate of aging with other primates. The maximum human life expectancy has increased by about three months per year since the mid-1800s, but that can be explained by fewer early and midlife deaths. Alberts found that the rate of decline during old age has stayed the same, mirroring other species. She believes that maximum human life span could be extended by continuing to “avert early and midlife deaths,” which simply increases the pool of people who could live a really long time.

Time will tell who’s right regarding the life span of our species. What’s clear is that certain lifestyles help individuals live longer than they otherwise would – including the genetically blessed. Harvard researchers found that healthy habits add nearly 15 years of life expectancy. “That’s over $100 trillion in health-care savings,” said Harvard biologist David Sinclair.

Not enough Americans can access healthy lifestyles, however, and we’re getting sick and dying earlier across economic levels compared with other countries. People under 65 in the richest areas of the United States have higher mortality than those in the poorest areas of Europe, according to a study published in September. “We’re going to pay if we don’t do something about this rising tide of disabled people,” said Judith Campisi, a biochemist at the Buck Institute for Research on Aging.

Findings from longevity research could support better health in old age, with fewer age-related diseases and disabilities. And interestingly, many scientists believe that a certain amount and type of stress can help, thanks to evolution. As Sinclair wrote in his 2019 book, “Lifespan”: “Our genes didn’t evolve for a life of pampered comfort. A little stress to induce hormesis once in a while likely goes a long way.”

“Hormesis” is a process in which various stressors — such as those related to diet and exercise — seem to activate genes that slow down cell growth and aging.

Using food to trick yourself

Stress that’s good for longevity can be caused by nutrition. Ideally, our ancestors enjoyed protein-rich red meat for peak energy and performance. But when hunting expeditions failed, people resorted to eating hardy plants. Today, our bodies still infer a state of scarcity if we consume lots of vegetables, switching on the longevity genes. Indeed, such a diet is associated with longer lives, according to the Harvard study. Becoming a full-fledged vegetarian probably isn’t necessary, but, to maximize what longevity experts call “healthspan,” at least 50 percent of protein should come from vegetable sources, Longo said.

He advises getting other proteins mostly from fatty fish while moderating your intake of starchy carbohydrates, such as pasta and potatoes. Research has shown that older people who routinely devour such carbs may be more likely to become cognitively impaired. Try to replace them sometimes with foods such as lentils or extra vegetables, which have more fiber and minerals than refined carbs, said Kris Verburgh, a nutrigerontologist and author of “The Longevity Code.”

Another signal of scarcity that seems to switch on longevity genes is the restriction of all foods, which has been shown by decades of animal studies to lengthen life span. Although water-only fasting over several days can be dangerous, “fasting mimicking” diets — very low-calorie five-day eating plans that trick the body into thinking it’s fasting while allowing some foods and nutrients — have been shown to be safer. Longo believes such diets “will play a major part in maximizing longevity.”

Research continues on various fasting regimens. In a preprint review, Matt Kaeberlein, a biogerontologist at the University of Washington, found limited evidence that avoiding food during specific windows of the day, without dropping overall calorie intake, increases life span in mice. When calories are reduced, some genetic strains of mice seem to benefit, but others actually die faster. Calorie restriction “could enhance longevity in some people while shortening lifespan in others,” Kaeberlein wrote.

“We’re beginning to find faults with some extreme diets,” Campisi said. The best approach, she said, “is dietary restriction without malnutrition.” The real benefit of fasting, she added, might simply come from losing weight. “Obesity is a risk factor for inflammation,” and chronic, low-grade inflammation can accelerate aging in a process known as inflammaging.

Sinclair eats just once per day, at dinnertime. “When you eat is perhaps more important than what you eat,” he said, referring to animal studies. “It’s easy to say mice aren’t humans, but there are some broad lessons.”

Exercising, but in moderation

Exercise can further simulate our ancestors’ stressful environments, some experts say, which can dupe your genes into extending your span of health. Just don’t do too much.

In August, the Mayo Clinic published research suggesting an optimal amount of exercise: People who played sports for 2.6 to 4.5 hours per week since the 1990s were about 40 percent less likely to have died than those who exercised less often. Cardio workouts may extend longevity by multiplying mitochondria, the “powerhouses” within cells. When scientists damage mitochondria in mice, the animals die faster, and mitochondrial dysfunction results in inflammaging in humans, Campisi said.

High-intensity interval training, or HIIT, may be particularly effective in adding to longevity. K. Sreekumaran Nair, a Mayo endocrinologist, found that 12 weeks of HIIT reversed many age-related differences in how older people synthesize proteins, buffering their mitochondria. Strength training may also partially reverse aspects of aging.

As with fasting, just don’t go overboard. “Some young guys want to do too much of everything,” Nair said. “There’s no data that working out beyond a certain level gives you better mitochondria.” Being very aerobically fit may reduce mortality risk, but the August paper suggests a Goldilocks sweet spot; exercising more than 10 hours per week was linked to shorter life spans. Previous research has shown an association between extreme exercise and health problems, such as premature aging of the heart.

Nair suggests doing 35 minutes of HIIT three days per week; doing two nonconsecutive days of strength training, focusing on core muscles, arms and legs, with three sets for each muscle group; and taking walks of 7,000 to 10,000 steps on the other two days. He also recommends trying to get at least three minutes of movement after every hour of sitting.

But keep in mind that these diet and exercise regimens can’t magically undo a lifetime of mistakes. A young person’s lifestyle “will echo for decades,” Sinclair warned.

Beyond diet and exercise

Sinclair noted another driver of longevity: long-term, loving relationships. In a nearly 80-year study, researchers found that the most important factor in a long, healthy life was having a close partner. Lynne Charnay, a 96-year-old actress who still performs onstage, attributes her longevity to marital bliss — a double dose of it. “I’ve had not one fabulous husband, but two!” Boxing regularly with her personal trainer in New York doesn’t hurt, either.

Another protective factor: optimism. In 2019, Boston University psychologist Lewina Lee found that optimism was associated with exceptional longevity. Take heart, Debbie Downers: Optimism can be cultivated through interventions. “While optimism is about 25 percent heritable,” Lee told me, “the rest is attributable to environmental influences.” That may partly explain why people entrenched in poverty, with little reason for optimism, die at much younger ages.

But residents of lower-income areas also have limited access to the heathy foods and opportunities cited above. That’s why experts on aging have called for policies that improve access to healthy lifestyles, especially as findings about exercise, nutrition and other anti-aging interventions continue to evolve, promising more years of health to those who can afford them.

“We’re still in the Wright brothers’ days of flight when it comes to longevity,” Sinclair said. “We still have a 747 and a Concorde to come, I hope, within our lifetimes.”

Source: Anchorage Daily News

New Research: Humans Could Live up to 150 Years

Emily Willingham wrote . . . . . . . . .

A study counts blood cells and footsteps to predict a hard limit to our longevity.

The chorus of the theme song for the movie Fame, performed by actress Irene Cara, includes the line “I’m gonna live forever.” Cara was, of course, singing about the posthumous longevity that fame can confer. But a literal expression of this hubris resonates in some corners of the world—especially in the technology industry. In Silicon Valley, immortality is sometimes elevated to the status of a corporeal goal. Plenty of big names in big tech have sunk funding into ventures to solve the problem of death as if it were just an upgrade to your smartphone’s operating system.

Yet what if death simply cannot be hacked and longevity will always have a ceiling, no matter what we do? Researchers have now taken on the question of how long we can live if, by some combination of serendipity and genetics, we do not die from cancer, heart disease or getting hit by a bus. They report that when omitting things that usually kill us, our body’s capacity to restore equilibrium to its myriad structural and metabolic systems after disruptions still fades with time. And even if we make it through life with few stressors, this incremental decline sets the maximum life span for humans at somewhere between 120 and 150 years. In the end, if the obvious hazards do not take our lives, this fundamental loss of resilience will do so, the researchers conclude in findings published on May 25 in Nature Communications.

“They are asking the question of ‘What’s the longest life that could be lived by a human complex system if everything else went really well, and it’s in a stressor-free environment?’” says Heather Whitson, director of the Duke University Center for the Study of Aging and Human Development, who was not involved in the paper. The team’s results point to an underlying “pace of aging” that sets the limits on lifespan, she says.

For the study, Timothy Pyrkov, a researcher at a Singapore-based company called Gero, and his colleagues looked at this “pace of aging” in three large cohorts in the U.S., the U.K. and Russia. To evaluate deviations from stable health, they assessed changes in blood cell counts and the daily number of steps taken and analyzed them by age groups.

For both blood cell and step counts, the pattern was the same: as age increased, some factor beyond disease drove a predictable and incremental decline in the body’s ability to return blood cells or gait to a stable level after a disruption. When Pyrkov and his colleagues in Moscow and Buffalo, N.Y., used this predictable pace of decline to determine when resilience would disappear entirely, leading to death, they found a range of 120 to 150 years. (In 1997 Jeanne Calment, the oldest person on record to have ever lived, died in France at the age of 122.)

The researchers also found that with age, the body’s response to insults could increasingly range far from a stable normal, requiring more time for recovery. Whitson says that this result makes sense: A healthy young person can produce a rapid physiological response to adjust to fluctuations and restore a personal norm. But in an older person, she says, “everything is just a little bit dampened, a little slower to respond, and you can get overshoots,” such as when an illness brings on big swings in blood pressure.

Measurements such as blood pressure and blood cell counts have a known healthy range, however, Whitson points out, whereas step counts are highly personal. The fact that Pyrkov and his colleagues chose a variable that is so different from blood counts and still discovered the same decline over time may suggest a real pace-of-aging factor in play across different domains.

Study co-author Peter Fedichev, who trained as a physicist and co-founded Gero, says that although most biologists would view blood cell counts and step counts as “pretty different,” the fact that both sources “paint exactly the same future” suggests that this pace-of-aging component is real.

The authors pointed to social factors that reflect the findings. “We observed a steep turn at about the age of 35 to 40 years that was quite surprising,” Pyrkov says. For example, he notes, this period is often a time when an athlete’s sports career ends, “an indication that something in physiology may really be changing at this age.”

The desire to unlock the secrets of immortality has likely been around as long as humans’ awareness of death. But a long life span is not the same as a long health span, says S. Jay Olshansky, a professor of epidemiology and biostatistics at the University of Illinois at Chicago, who was not involved in the work. “The focus shouldn’t be on living longer but on living healthier longer,” he says.

“Death is not the only thing that matters,” Whitson says. “Other things, like quality of life, start mattering more and more as people experience the loss of them.” The death modeled in this study, she says, “is the ultimate lingering death. And the question is: Can we extend life without also extending the proportion of time that people go through a frail state?”

The researchers’ “final conclusion is interesting to see,” says Olshansky. He characterizes it as “Hey, guess what? Treating diseases in the long run is not going to have the effect that you might want it to have. These fundamental biological processes of aging are going to continue.”

The idea of slowing down the aging process has drawn attention, not just from Silicon Valley types who dream about uploading their memories to computers but also from a cadre of researchers who view such interventions as a means to “compress morbidity”—to diminish illness and infirmity at the end of life to extend health span. The question of whether this will have any impact on the fundamental upper limits identified in the Nature Communications paper remains highly speculative. But some studies are being launched—testing the diabetes drug metformin, for example—with the goal of attenuating hallmark indicators of aging.

In this same vein, Fedichev and his team are not discouraged by their estimates of maximum human life span. His view is that their research marks the beginning of a longer journey. “Measuring something is the first step before producing an intervention,” Fedichev says. As he puts it, the next steps, now that the team has measured this independent pace of aging, will be to find ways to “intercept the loss of resilience.”

Source : Scientific American

Feel Younger Than Your Age? You Might Live Longer

Alan Mozes wrote . . . . . . . . .

Can feeling young at heart, or at least younger than your actual age, help older people live healthier, longer lives?

Yes, according to researchers in Germany.

“Individuals who feel younger than they chronologically are seem to benefit from their younger subjective age in various aspects,” explained study lead author Markus Wettstein.

Surveying more than 5,000 middle-aged adults and seniors, his team found that feeling younger seems to create a protective force field against stress. And the “connection seems to work via various pathways,” said Wettstein, who was a researcher with the German Centre of Gerontology in Berlin when the study was conducted.

On the one hand, he noted that stress reduction due to a youthful self-perception may translate into tangible physical benefits, including staving off the threat of systemic inflammation.

Having a youthful sense of self may also shape behavior in positive ways that help to keep physical and mental well-being intact.

“Individuals who feel younger [may] engage in health-protective behaviors,” Wettstein said. For example, they may be more physically active than those who don’t feel quite as young.

In addition, perceiving oneself to be younger might also be a motivating force behind self-improvement, giving folks a greater “health-enhancing” confidence in their ability to accomplish things successfully and effectively.

The study participants’ average age was 64. All were enrolled in a larger ongoing study on aging and physical and mental health.

Over three years, they were asked to indicate how old they felt, how much stress they experienced, and how well they could perform basic everyday activities, such as walking, dressing and/or bathing.

Overall, those who reported greater stress also indicated a greater decline in their ability to execute those routine tasks. And that association was generally found to be stronger as people aged.

But the link between stress and impairment was notably weaker among those who indicated they felt younger than their true age. In fact, feeling younger was found to be particularly protective the longer-toothed one actually got.

All of this suggests that interventions designed to help older adults feel younger than they are might help seniors stay healthier and live longer, Wettstein and his colleagues observed.

One U.S. researcher not involved in the study said that prior efforts to explore the question of “subjective age” seem to support the German team’s findings.

“I don’t find this surprising at all, given the considerable prior research that has shown that feeling younger than your actual age is associated with a wide range of indicators of better health,” said James Maddux. He’s a professor emeritus from George Mason University’s Department of Psychology, and a senior scholar with GMU’s Center for the Advancement of Well-Being, in Fairfax, Va.

“What this study tells us that’s new,” Maddux said, “is that there seems to be an indirect path from feeling younger and being healthier, in that feeling younger seems to protect people from the unhealthy effects of stress. And that this effect gets stronger as we get older.”

Maddux suggested that feeling young may ultimately give rise to a so-called “virtuous cycle,” causing people to take better care of themselves, and thereby refueling a youthful sense of self.

“I just lost the 10 pounds I gained during the pandemic,” Maddux volunteered. “And I certainly feel younger than I did three months ago now that I can see my abs again!”

Still, Wettstein and his team cautioned that prior research suggests the potential health benefits of youthful perceptions may evaporate if the gap between how young one feels and how old one actually is grows too large.

The debate, said Wettstein, is “whether too-optimistic perspectives on one’s own aging might have disadvantages, as those over-optimistic individuals might not anticipate certain potential age-related losses, and are thus unprepared when they set in.”

For now, more research is required to determine what degree of “positivity” in views on aging — and which subjective age — is most beneficial for health, longevity and well-being, he added.

The findings were published in the Psychology and Aging.

Source: HealthDay

Beyond Genes and Environment, Random Variations Play Important Role in Longevity

A new model of aging takes into account not only genetics and environmental exposures but also the tiny changes that randomly arise at the cellular level.

University Professor Caleb Finch introduced the “Tripartite Phenotype of Aging” as a new conceptual model that addresses why lifespan varies so much, even among human identical twins who share the same genes. Only about 10 to 35 percent of longevity can be traced to genes inherited from our parents, Finch mentioned.

Finch authored the paper introducing the model with one of his former graduate students, Amin Haghani, who received his PhD in the Biology of Aging from the USC Leonard Davis School in 2020 and is now a postdoctoral researcher at UCLA. In the article, they propose that the limited heritability of aging patterns and longevity in humans is an outcome of gene-environment interactions, together with stochastic, or chance, variations in the body’s cells. These random changes can include cellular changes that happen during development, molecular damage that occurs later in life, and more.

“We wanted to introduce a conceptual map and some new terminology that will motivate a more comprehensive understanding of what the limitations of genetic determinants in aging are, how important it is to consider the genetic variance in relationship to the environment, and include this new domain of stochastic variations, which is very well recognized by different fields,” said Finch, who holds the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School. “It hasn’t really been put in a formal context in which the complete package can be discussed, and that’s what I hope our article achieves.”

Expanding on the exposome

The new model is a natural extension of the idea of the exposome, which was first proposed by cancer epidemiologist Christopher Paul Wild in 2005 to draw attention to the need for more data on lifetime exposure to environmental carcinogens. The exposome concept illustrates how external factors, ranging from air pollution and socioeconomic status to individual diet and exercise patterns, interact with endogenous, or internal, factors such as the body’s microbiome and fat deposits.

The exposome is now a mainstream model, eclipsing previous characterizations of environmental factors as affecting risk “one by one.” Finch has previously expanded on the exposome concept with the introduction of the Alzheimer’s disease exposome. The gero-exposome now considers how genes and the environment interact over the lifespan to shape how we age.

The new model illustrates that cell-by-cell variations in gene expression, variations arising during development, random mutations, and epigenetic changes – turning genes “off” or “on” – should be explicitly considered apart from traditional genetic or environmental research regarding aging, Finch said. More detailed study into these chance processes has been enabled by cutting-edge research techniques, including the study of gene transcription within single cells as well as ChIP-sequencing, which can illustrate how individual proteins interact with DNA.

Effects of happenstance on health

In the paper, Finch and Haghani discussed several examples of how risks of age-related disease are poorly predicted by DNA alone but are heavily influenced by environmental exposures as well as the time and duration of the exposure, including during development or over the course of decades.

One well-known example of a gene that is associated with increased Alzheimer’s risk is ApoE-4; however, having the ApoE-4 gene doesn’t definitively mean someone will get Alzheimer’s. Studies in both mice and humans revealed that ApoE-4 and clusters of related genes interact with exposures such as air pollution or cigarette smoke to influence risk, and Alzheimer’s patients also show differences in their epigenetics as compared to individuals without the disease.

He added that the idea of environmental exposure can stretch farther than many people expect. Disease exposure earlier in life can affect health risks later in life – and across generations.

“The environment that we’re exposed to goes back to our grandmothers because the egg we came from was in our mother’s ovaries at the time of her birth,” he explained. “So that means, in my case, because my grandmother was born in 1878, I might very well carry some traces of the 19th century environment, which included much greater exposure to infectious disease because there were no antibiotics.”

Finch said that he hopes the more comprehensive model on how genes, environment, and random variations over time interact to influence aging prompt a new discussion of what the rapidly developing field of precision medicine needs to take into account to promote healthy aging.

“I think that there will be a much greater recognition in understanding individual patterns of aging,” he said. “We can only define it up to a certain point by knowing the genetic risks; we must have a more comprehensive understanding of the lifetime exposures, environments and lifestyles of an individual to have a better understanding of genetic risk for particular diseases.”

Source: EurekAlert!

Gut Microbiome Implicated in Healthy Aging and Longevity

The gut microbiome is an integral component of the body, but its importance in the human aging process is unclear. ISB researchers and their collaborators have identified distinct signatures in the gut microbiome that are associated with either healthy or unhealthy aging trajectories, which in turn predict survival in a population of older individuals. The work was just published in the journal Nature Metabolism.

The research team analyzed gut microbiome, phenotypic and clinical data from over 9,000 people – between the ages of 18 and 101 years old – across three independent cohorts. The team focused, in particular, on longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old), allowing them to track health and survival outcomes.

The data showed that gut microbiomes became increasingly unique (i.e. increasingly divergent from others) as individuals aged, starting in mid-to-late adulthood, which corresponded with a steady decline in the abundance of core bacterial genera (e.g. Bacteroides) that tend to be shared across humans.

Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. This gut uniqueness signature was highly correlated with several microbially-derived metabolites in blood plasma, including one – tryptophan-derived indole – that has previously been shown to extend lifespan in mice. Blood levels of another metabolite – phenylacetylglutamine – showed the strongest association with uniqueness, and prior work has shown that this metabolite is indeed highly elevated in the blood of centenarians.

“This uniqueness signature can predict patient survival in the latest decades of life,” said ISB Research Scientist Dr. Tomasz Wilmanski, who led the study. Healthy individuals around 80 years of age showed continued microbial drift toward a unique compositional state, but this drift was absent in less healthy individuals.

“Interestingly, this uniqueness pattern appears to start in mid-life – 40-50 years old – and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age,” Wilmanski said. For example, indoles are known to reduce inflammation in the gut, and chronic inflammation is thought to be a major driver in the progression of aging-related morbidities.

“Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health,” said microbiome specialist Dr. Sean Gibbons, co-corresponding author of the paper. “Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: 1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and 2) the maintenance of core microbes in less healthy individuals.”

This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood.

“This is exciting work that we think will have major clinical implications for monitoring and modifying gut microbiome health throughout a person’s life,” said ISB Professor Dr. Nathan Price, co-corresponding author of the paper.

This research project was conducted by ISB and collaborators from Oregon Health and Science University, University of California San Diego, University of Pittsburgh, University of California Davis, Lifestyle Medicine Institute, and University of Washington. It was supported in part by a Catalyst Award in Healthy Longevity from the National Academy of Medicine, and the Longevity Consortium of the National Institute on Aging.

Source: ISB