Researchers have discovered an explanation for why cerebral cavernous malformations (CCMs) — clusters of dilated blood vessels in the brain — can suddenly grow to cause seizures or stroke. Specifically, they found that a specific, acquired mutation in a cancer-causing gene (PIK3CA) could exacerbate existing CCMs in the brain. Furthermore, repurposing an already existing anticancer drug showed promise in mouse models of CCMs in improving brain-vascular health and preventing bleeding into the brain tissue.
Previous studies linked the initial formation of CCMs to various environmental factors, including differences in the gut microbiome, and inactivating mutations in three specific genes collectively known as the “CCM complex.” While these changes are enough to cause small malformations to form in the brain, they didn’t explain why some suddenly expand in size, resulting in seizures or stroke.
Using mouse genetic models of CCM formation, the researchers discovered that it is the additional “hit” that stimulates the known cancer-causing gene PIK3CA and leads to the rapid growth of existing CCMs. When they examined resected human CCM tissue, they saw the same genes were involved, which supports the idea of a “cancer-like” mechanism for accelerated blood vessel malformation growth in which small quiescent CCMs become “malignant” after a new gene mutation occurs.
In cancer, the PIK3CA mutation results in an increase in PI3K-mTOR signaling, which is a well-established drug target for the treatment of tumors. Rapamycin is an FDA-approved drug that inhibits that same signaling pathway and has been used to treat malformations in the veins and lymphatic system. Here, rapamycin significantly reduced CCM formation in genetic mouse models, suggesting it could be potentially used as a treatment.
The study was led by Mark L. Kahn, M.D. at the Perelman School of Medicine, University of Pennsylvania, Philadelphia. His team continues to study what causes CCM formation and growth, and proposes that further analyses of human CCM lesions and clinical testing of rapamycin and similar drugs is necessary to determine whether this mechanism can be a target for therapy.
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Even though more and more vaccines against the coronavirus are being administered all over the world, many countries are still battling with outbreaks and face difficulties providing help to those in need.
One of those countries is Brazil. Here, they are facing a massive second wave outbreak, many daily deaths and instances of the health care systems collapsing. In the city of Manaus things have looked exceptionally bleak from December and through to the early spring.
The city was hit so hard by the first wave in 2020 that it was actually thought to be one of the few places in the world to have reached herd immunity. An estimated 75 percent of the population in the city had been infected. But then the second wave hit in November and December.
Now, a new study published in Science with collaborators from Brazil, the UK and University of Copenhagen has shed a light on why Manaus is facing these difficulties again.
“Our main explanation is that there is an aggressive variant of the coronavirus called P.1 which seems be the cause of their problems. Our epidemiological model indicates that P.1 is likely to be more transmissible than previous strains of coronavirus and likely to be able to evade immunity gained from infection with other strains,” says corresponding author to the new study, Samir Bhatt, a researcher at the Department of Public Health at University of Copenhagen.
Emerged in November
The researchers used many forms of data from Manaus to characterize P.1 and its properties including 184 samples of genetic sequencing data. They find that genetically speaking P.1 is different from the previous strains of coronavirus. It has acquired 17 mutations including an important trio of mutations in the spike protein (K417T, E484K and N501Y).

Listen to This ArticleAudio Recording by AudmTo hear more audio stories from publications like The New York Times, download Audm for iPhone or Android.In 1990, not long after Jean-Marie Robine and Michel Allard began conducting a nationwide study of French centenarians, one of their software programs spat out an error message. An individual in the study was marked as 115 years old, a number outside the program’s range of acceptable age values. They called their collaborators in Arles, where the subject lived, and asked them to double-check the information they had provided, recalls Allard, who was then the director of the IPSEN Foundation, a nonprofit research organization. Perhaps they made a mistake when transcribing her birth date? Maybe this Jeanne Calment was actually born in 1885, not 1875? No, the collaborators said. We’ve seen her birth certificate. The data is correct.Calment was already well known in her hometown. Over the next few years, as rumors of her longevity spread, she became a celebrity. Her birthdays, which had been local holidays for a while, inspired national and, eventually, international news stories. Journalists, doctors and scientists began crowding her nursing-home room, eager to meet la doyenne de l’humanité. Everyone wanted to know her story.Calment lived her entire life in the sunburned clay-and-cobble city of Arles in the South of France, where she married a second cousin and moved into a spacious apartment above the store he owned. She never needed to work, instead filling her days with leisurely pursuits: bicycling, painting, roller skating and hunting. She enjoyed a glass of port, a cigarette and some chocolate nearly every day. In town, she was known for her optimism, good humor and wit. (“I’ve never had but one wrinkle,” she once said, “and I’m sitting on it.”)By age 88, Calment had outlived her parents, husband, only child, son-in-law and grandson. As she approached her 110th birthday, she was still living alone in her cherished apartment. One day, during a particularly severe winter, the pipes froze. She tried to thaw them with a flame, accidentally igniting the insulating material. Neighbors noticed the smoke and summoned the fire brigade, which rushed her to a hospital. Following the incident, Calment moved into La Maison du Lac, the nursing home situated on the hospital’s campus, where she would live until her death at age 122 in 1997. In 1992, as Calment’s fame bloomed, Robine and Allard returned to her file. Clearly, here was someone special — someone who merited a case study. Arles was just an hour’s drive from the village where Robine, a demographer at the French National Institute of Health and Medical Research, lived at the time. He decided to arrange a visit. At La Maison du Lac, he introduced himself to the medical director, Victor Lèbre, and explained that he wanted to interview Calment. Lèbre replied that it was too late; Calment, he said, was completely deaf. But he agreed to let him meet the grande dame anyway. They walked down a long concrete corridor and into a small and spare room.“Hello, Madame Calment,” Lèbre said.“Good morning, doctor,” she answered without hesitation.Lèbre was so shocked that he grabbed Robine by the arm and rushed him down the corridor back to his office, where he interrogated the nurses about Calment’s hearing. Apparently she could hear quite well at times, but experienced periods of near deafness; Lèbre had most likely mistaken one of those interludes for a permanent condition. Upon returning to Calment’s room, Robine saw her properly for the first time. She was sitting by the window in an armchair that dwarfed her shrunken frame. Her eyes, milky with cataracts, could distinguish light from dark, but did not focus on any place in particular. Her plain gray clothes appeared to be several decades old.During that first meeting, Robine and Calment mostly exchanged pleasantries and idle chatter. Over the next few years, however, Robine and Allard, in collaboration with several other researchers and archivists, interviewed Calment dozens of times and thoroughly documented her life history, verifying her age and cementing her reputation as the oldest person who ever lived. Since then, Calment has become something of an emblem of the ongoing quest to answer one of history’s most controversial questions: What exactly is the limit on the human life span?As medical and social advances mitigate diseases of old age and prolong life, the number of exceptionally long-lived people is increasing sharply. The United Nations estimates that there were about 95,000 centenarians in 1990 and more than 450,000 in 2015. By 2100, there will be 25 million. Although the proportion of people who live beyond their 110th birthday is far smaller, this once-fabled milestone is also increasingly common in many wealthy nations. The first validated cases of such “supercentenarians” emerged in the 1960s. Since then, their global numbers have multiplied by a factor of at least 10, though no one knows precisely how many there are. In Japan alone, the population of supercentenarians grew to 146 from 22 between 2005 and 2015, a nearly sevenfold increase. Given these statistics, you might expect that the record for longest life span would be increasing, too. Yet nearly a quarter-century after Calment’s death, no one is known to have matched, let alone surpassed, her 122 years. The closest was an American named Sarah Knauss, who died at age 119, two years after Calment. The oldest living person is Kane Tanaka, 118, who resides in Fukuoka, Japan. Very few people make it past 115. (A few researchers have even questioned whether Calment really lived as long as she claimed, though most accept her record as legitimate based on the weight of biographical evidence.)As the global population approaches eight billion, and science discovers increasingly promising ways to slow or reverse aging in the lab, the question of human longevity’s potential limits is more urgent than ever. When their work is examined closely, it’s clear that longevity scientists hold a wide range of nuanced perspectives on the future of humanity. Historically, however — and somewhat flippantly, according to many researchers — their outlooks have been divided into two broad camps, which some journalists and researchers call the pessimists and the optimists. Those in the first group view life span as a candle wick that can burn for only so long. They generally think that we are rapidly approaching, or have already reached, a ceiling on life span, and that we will not witness anyone older than Calment anytime soon.In contrast, the optimists see life span as a supremely, maybe even infinitely elastic band. They anticipate considerable gains in life expectancy around the world, increasing numbers of extraordinarily long-lived people — and eventually, supercentenarians who outlive Calment, pushing the record to 125, 150, 200 and beyond. Though unresolved, the long-running debate has already inspired a much deeper understanding of what defines and constrains life span — and of the interventions that may one day significantly extend it.The theoretical limits on the length of a human life have vexed scientists and philosophers for thousands of years, but for most of history their discussions were largely based on musings and personal observations. In 1825, however, the British actuary Benjamin Gompertz published a new mathematical model of mortality, which demonstrated that the risk of death increased exponentially with age. Were that risk to continue accelerating throughout life, people would eventually reach a point at which they had essentially no chance of surviving to the next year. In other words, they would hit an effective limit on life span.Instead, Gompertz observed that as people entered old age, the risk of death plateaued. “The limit to the possible duration of life is a subject not likely ever to be determined,” he wrote, “even should it exist.” Since then, using new data and more sophisticated mathematics, other scientists around the world have uncovered further evidence of accelerating death rates followed by mortality plateaus not only in humans but also in numerous other species, including rats, mice, shrimp, nematodes, fruit flies and beetles. In 2016, an especially provocative study in the prestigious research journal Nature strongly implied that the authors had found the limit to the human life span. Jan Vijg, a geneticist at the Albert Einstein College of Medicine, and two colleagues analyzed decades’ worth of mortality data from several countries and concluded that although the highest reported age at death in these countries increased rapidly between the 1970s and 1990s, it had failed to rise since then, stagnating at an average of 114.9 years. Human life span, it seemed, had arrived at its limit. Although some individuals, like Jeanne Calment, might reach staggering ages, they were outliers, not indicators of a continual lengthening of life.‘Could someone run a two-minute mile? No. The human body is incapable of moving that fast based on anatomical limitations.’While a few scientists from the more pessimistic tradition applauded the study, many researchers sternly critiqued its methods, in particular the bold generalization based on what one commentary called a “limited, noisy set of data.” Nearly a dozen rebuttals appeared in Nature and other journals. James Vaupel, the founding director of the Max Planck Institute for Demographic Research and a staunch critic of the idea that the human life span has reached its limit, called the study a travesty and told the science journalist Hester van Santen that the authors “just shoveled the data into their computer like you’d shovel food into a cow.”Robine remembers the furor well. He was one of several peer reviewers whom Nature recruited to evaluate the study by Vijg and his co-authors before publication. The first draft did not satisfy Robine’s standards, because it focused only on the United States and relied on data he considered incomplete. Among other changes, he recommended using the more comprehensive International Database on Longevity, which he and Vaupel developed with colleagues. Van Santen reported in a peer-review post-mortem that, based on the substantial criticism by Robine and one of the other reviewers, Nature initially declined to publish the study. After Vijg and his co-authors sent Nature a thoroughly revised version, however, Robine conceded that the study was sound enough to publish, though he still disagreed with its conclusions. (Vijg stands by the methodology and conclusions of the study.)Two years later, in 2018, the equally prestigious journal Science published a study that completely contradicted the one in Nature. The demographers Elisabetta Barbi of the University of Rome and Kenneth Wachter of the University of California, Berkeley, along with several colleagues, examined the survival trajectories of nearly 4,000 Italians and concluded that, while the risk of death increased exponentially up to age 80, it then slowed and eventually plateaued. Someone alive at 105 had about a 50 percent chance of living to the next year. The same was true at 106, 107, 108 and 109. Their findings, the authors wrote, “strongly suggest that longevity is continuing to increase over time, and that a limit, if any, has not been reached.” Many of the disputes over human longevity studies center on the integrity of different data sets and the varying statistical methods researchers use to analyze them. Where one group of scientists perceives a clear trend, another suspects an illusion. Robine finds the debate exciting and essential. “I’m not convinced by my colleagues’ suggesting that life is or is not limited,” he told me. “I think the question is still here. We don’t yet know the best kind of analysis or study design to use to tackle this question. The most important thing to do today is to keep collecting the data.”On their own, however, life-span statistics can tell us only so much. Such data have been available for centuries and have clearly not settled the debate. The number of supercentenarians may still be too small to support unequivocal conclusions about mortality rates in extreme old age. But in more recent decades, scientists have made considerable progress toward understanding the evolutionary origins of longevity and the biology of aging. Instead of fixating on human demographics, this research considers all species on the planet and tries to derive general principles about duration of life and timing of death. “I’m a little surprised that anyone today would question whether or not there is a limit,” S. Jay Olshansky, an expert on longevity and a professor in the School of Public Health at the University of Illinois at Chicago, told me. “It doesn’t really matter whether there is a plateau of mortality or not in extreme old age. There are so few people that make it up there, and the risk of death at that point is so high, that most people aren’t going to live much beyond the limits we see today.”Olshansky, 67, has argued for decades that life span is obviously limited and that the mathematical models of feuding demographers are secondary to the biological realities of aging. He likes to make an analogy to athletics: “Could someone run a two-minute mile? No. The human body is incapable of moving that fast based on anatomical limitations. The same thing applies to human longevity.”He is so thoroughly convinced of his position that he has backed it with an investment that may eventually grow to a sizable fortune for him or his heirs. In 2000, Steven Austad, a biologist now at the University of Alabama, Birmingham, told Scientific American, “The first 150-year-old person is probably alive right now.” When Olshansky disagreed, the two struck up a friendly bet: Each put $150 in an investment fund and signed a contract stipulating that the winner or his descendants would claim the returns in 2150. After the Vijg paper was published, they doubled their contributions. Olshansky originally invested the funds in gold and later in Tesla. He estimates the value will be well over $1 billion when it’s time to collect. “Oh, I am going to win,” Olshansky said when I asked him how he currently feels about the wager. “Ultimately, biology will determine which one of us is right. That’s why I’m so confident.”Photo illustration by Maurizio Cattelan and Pierpaolo FerrariEmbedded in the question of the human life span’s limits is a more fundamental enigma: Why do we — why does any organism — get old and die in the first place? As the eminent physicist Richard Feynman put it in a 1964 lecture, “There is nothing in biology yet found that indicates the inevitability of death.” Some organisms seem to be living proof of this claim. Scientists recently drilled into sediments deep beneath the seafloor and unearthed microbes that had probably survived “in a metabolically active form” for more than 100 million years. Pando, a 106-acre clonal colony of genetically identical aspen trees connected by a single root system in Utah, is thought to have sustained itself for as long as 14,000 years and counting.A few creatures are so ageless that some scientists regard them as biologically immortal. Hydra, tiny relatives of jellyfish and corals, do not appear to age at all and can regenerate whole new bodies when sliced into pieces. When injured or threatened, a sexually mature Turritopsis dohrnii, the immortal jellyfish, can revert to its juvenile stage, mature and revert again, potentially forever. Biologically immortal organisms are not impervious to death — they can still perish from predation, lethal injury or infection — but they do not seem to die of their own accord. Theoretically, any organism with a continual supply of energy, a sufficient capacity for self-maintenance and repair and the good fortune to evade all environmental hazards could survive until the end of the universe.Why, then, do so many species expire so dependably? Most longevity researchers agree that aging, the set of physical processes of damage and decay that result in death, is not an adaptive trait shaped by natural selection. Rather, aging is a byproduct of selection’s waning power over the course of an organism’s life. Selection acts most strongly on genes and traits that help living creatures survive adolescence and reproduce. In many species, the few individuals who make it to old age are practically invisible to natural selection because they are no longer passing on their genes, nor helping raise their relatives’ progeny.As the British biologist Peter Medawar observed in the 1950s, harmful genetic mutations that are not expressed until late in life could accumulate across generations because selection is too weak to remove them, eventually resulting in specieswide aging. The American biologist George C. Williams elaborated on Medawar’s ideas, adding that some genes may be beneficial in youth but detrimental later on, when selection would overlook their disadvantages. Similarly, in the 1970s, the British biologist Thomas Kirkwood proposed that aging was partly due to an evolutionary trade-off between growth and reproduction on the one hand and day-to-day maintenance on the other. Devoting resources to maintenance is advantageous only if an organism is likely to continue surviving and reproducing. For many organisms, external threats are too great and numerous to endure for very long, so there is not much evolutionary pressure to preserve their bodies in old age, resulting in their deterioration.But that still leaves the question of why there is such huge variation in life span among species. Biologists think life span is largely determined by a species’ anatomy and lifestyle. Small and highly vulnerable animals tend to reproduce quickly and die not long after, whereas larger animals, and those with sophisticated defenses, usually reproduce later in life and live longer overall. Ground-dwelling birds, for instance, often have shorter life spans than strong-winged, tree-nesting species, which are less susceptible to predators. Naked mole rats, which enjoy the cooperative benefits of tight-knit social groups and the protection of subterranean chambers, live five to 10 times longer than other similarly sized mammals. A few species, like stalwart clonal trees with resilient root systems, are so well protected against environmental hazards that they don’t have to prioritize early growth and reproduction over long-term maintenance, allowing them to live an extraordinarily long time. Others, like the immortal jellyfish and hydra, are potentially indefinite, because they have retained primordial powers of rejuvenation that have been relegated to pockets of stem cells in most adult vertebrates.Humans have never belonged to the select society of the everlasting. We most likely inherited fairly long life spans from our last common ancestor with chimpanzees, which may have been a large, intelligent, social ape that lived in trees away from ground predators. But we never out-evolved the eventual senescence that is part of being a complex animal with all manner of metabolically costly adaptations and embellishments.As the years pass, our chromosomes contract and fracture, genes turn on and off haphazardly, mitochondria break down, proteins unravel or clump together, reserves of regenerative stem cells dwindle, bodily cells stop dividing, bones thin, muscles shrivel, neurons wither, organs become sluggish and dysfunctional, the immune system weakens and self-repair mechanisms fail. There is no programmed death clock ticking away inside us — no precise expiration date hard-wired into our species — but, eventually, the human body just can’t keep going.Social advances and improving public health may further increase life expectancy and lift some supercentenarians well beyond Calment’s record. Even the most optimistic longevity scientists admit, however, that at some point these environmentally induced gains will run up against human biology’s limits — unless, that is, we fundamentally alter our biology.Many scientists who study aging think that biomedical breakthroughs are the only way to substantially increase the human life span, but some doubt that anyone alive today will witness such radical interventions; a few doubt they are even possible. In any case, longevity scientists agree, significantly elongating life without sustaining well-being is pointless, and enhancing vitality in old age is valuable regardless of gains in maximum life span.One of the many obstacles to these goals is the overwhelming complexity of aging in mammals and other vertebrates. Researchers have achieved astonishing results by tweaking the genome of the roundworm C. elegans, extending its life span nearly 10 times — the equivalent of a person’s living 1,000 years. Although scientists have used caloric restriction, genetic engineering and various drugs to stretch life span in more complex species, including fish, rodents and monkeys, the gains have never been as sharp as in roundworms, and the precise mechanisms underlying these changes remain unclear.‘Cells can clean themselves up, they can get rid of old proteins, they can rejuvenate, if you turn on the youthful genes through this reset process.’More recently, however, researchers have tested particularly innovative techniques for reversing and postponing some aspects of aging, with tentative but promising results. James Kirkland, an expert on aging at the Mayo Clinic in Rochester, Minn., has demonstrated with colleagues that certain drug cocktails purge old mice of senescent cells, granting them more than a month of additional healthy living. Their research has already inspired numerous human clinical trials. At the same time, at the University of California, Berkeley, the married bioengineers Irina and Michael Conboy are investigating ways to filter or dilute aged blood in rodents to remove molecules that inhibit healing, which in turn stimulates cellular regeneration and the production of revitalizing compounds. In a study published in Nature in December 2020, David Sinclair, a director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School, along with colleagues, partly restored vision in middle-aged and ailing mice by reprogramming their gene expression. The researchers injected the mice’s eyes with a benign virus carrying genes that revert mature cells to a more supple, stem-cell-like state, which allowed their neurons to regenerate — an ability that mammals usually lose after infancy. “Aging is far more reversible than we thought,” Sinclair told me. “Cells can clean themselves up, they can get rid of old proteins, they can rejuvenate, if you turn on the youthful genes through this reset process.”Known for his boyish features and sanguine predictions, Sinclair, 51, and several of his family members (including his dogs) follow versions of his life-prolonging regimen, which has, over the years, included regular exercise, sauna steams and ice baths, a two-meal-a-day mostly vegetarian diet, the diabetes drug metformin (which is purported to have anti-aging properties) and several vitamins and supplements, like the once-hyped but ultimately disappointing red-wine miracle molecule resveratrol. Sinclair has also founded at least 12 biotech companies and serves on the boards of several more, one of which is already pursuing human clinical trials of a gene therapy based on his recent Nature study. In a talk at Google, he envisioned a future in which people receive similar treatments every decade or so to undo the effects of aging throughout the body. “We don’t know how many times you can reset,” he said. “It might be three, it might be 3,000. And if you can reset your body 3,000 times, then things get really interesting. I don’t know if any of you want to live for 1,000 years, but I also don’t know if it’s going to be possible, but these are the questions we have to start thinking about. Because it’s not a question of if — it’s now a question of when.” Longevity scientists who favor the idea of living for centuries or longer tend to speak effusively of prosperity and possibility. As they see it, sustaining life and promoting health are intrinsically good and, therefore, so are any medical interventions that accomplish this. Biomedically extended longevity would not only revolutionize general well-being by minimizing or preventing diseases of aging, they say, it would also vastly enrich human experience. It would mean the chance for several fulfilling and diverse careers; the freedom to explore much more of the world; the joy of playing with your great-great-great-grandchildren; the satisfaction of actually sitting in the shade of the tree you planted so long ago. Imagine, some say, how wise our future elders could be. Imagine what the world’s most brilliant minds could accomplish with all that time. ‘We still don’t know how to avoid frailty.’In sharp contrast, other experts argue that extending life span, even in the name of health, is a doomed pursuit. Perhaps the most common concern is the potential for overpopulation, especially considering humanity’s long history of hoarding and squandering resources and the tremendous socioeconomic inequalities that already divide a world of nearly eight billion. There are still dozens of countries where life expectancy is below 65, primarily because of problems like poverty, famine, limited education, disempowerment of women, poor public health and diseases like malaria and H.I.V./AIDS, which novel and expensive life-extending treatments will do nothing to solve.Lingering multitudes of superseniors, some experts add, would stifle new generations and impede social progress. “There is a wisdom to the evolutionary process of letting the older generation disappear,” said Paul Root Wolpe, the director of the Center for Ethics at Emory University, during one public debate on life extension. “If the World War I generation and World War II generation and perhaps, you know, the Civil War generation were still alive, do you really think that we would have civil rights in this country? Gay marriage?”In her final years at La Maison du Lac, the once-athletic Jeanne Calment was essentially immobile, confined to her bed and wheelchair. Her hearing continued to decline, she was virtually blind and she had trouble speaking. At times, it was not clear that she was fully aware of her surroundings. By some accounts, those in charge of Calment’s care failed to shield her from undue commotion and questionable interactions as journalists, tourists and spectators bustled in and out of her room. Following the release of an investigative documentary, the hospital director barred all visitors. The last time Robine saw her was shortly after her 120th birthday. About two years later, in the midst of an especially hot summer, Jeanne Calment died alone in her nursing-home room from unknown causes and was quickly buried. Only a few people were permitted to attend her funeral. Robine and Allard were not among them. Neither was Calment’s family: All her close relatives had been dead for more than three decades. “Today, more people are surviving the major diseases of old age and entering a new phase of their life in which they become very weak,” Robine said. “We still don’t know how to avoid frailty.”Perhaps the most unpredictable consequence of uncoupling life span from our inherited biology is how it would alter our future psychology. All of human culture evolved with the understanding that earthly life is finite and, in the grand scheme, relatively brief. If we are one day born knowing that we can reasonably expect to live 200 years or longer, will our minds easily accommodate this unparalleled scope of life? Or is our neural architecture, which evolved amid the perils of the Pleistocene, inherently unsuited for such vast horizons? Scientists, philosophers and writers have long feared that a surfeit of time would exhaust all meaningful experience, culminating in debilitating levels of melancholy and listlessness. Maybe the desire for all those extra years masks a deeper longing for something unattainable: not for a life that is simply longer, but for one that is long enough to feel utterly perfect and complete.In Jorge Luis Borges’s short story “The Immortal,” a Roman military officer stumbles upon a “secret river that purifies men of death.” After drinking from it and spending eons in deep thought, he realizes that death imbues life with value, whereas, for immortals, “Nothing can occur but once, nothing is preciously in peril of being lost.” Determined to find the antidote to everlasting life, he wanders the planet for nearly a millennium. One day, he drinks from a spring of clear water on the Eritrean coast and shortly thereafter scratches the back of his hand on a thorny tree. Startled by an unfamiliar twinge of pain, he searches for a sign of injury. As a drop of blood slowly pools on his skin — proof of his restored mortality — he simply watches, “incredulous, speechless, and in joy.”Ferris Jabr is a contributing writer for the magazine. His January 2019 cover story on the evolution of beauty is featured in the latest edition of The Best American Science and Nature Writing.

Age may adversely affect women’s fertility by impairing levels of RNA molecules which in turn alter the function of genes involved in key biological pathways during the final maturation stage of a human egg cell, according to the findings of a new study published today in the journal Aging Cell.
Researchers from the Centre for Genomic Regulation (CRG), the Centro Nacional de Análisis Genómico (CNAG-CRG) and Clínica Eugin sequenced the RNA molecules, also known as the transcriptome, within oocytes to understand which genes are affected in their activity by age. They used single-cell sequencing to analyse the transcriptome of 72 individual oocytes from 37 donors between 18 and 43 years of age.
They found that the number of transcripts for genes involved in chromosome segregation and RNA processing increased progressively with age, while the number of transcripts related to mitochondrial metabolism decreased.
However, these age-related changes to the transcriptome only occurred when egg cells reached their final stage of development during in vitro maturation. The transcriptome was less affected by age in immature egg cells. According to the researchers, the findings suggest that age may influence an oocyte’s ability to process gene products critical for the last steps of their development.
Further analyses revealed a number of potential master regulator genes, which are genes that occupy the very top of a regulatory hierarchy, that are affected by age. Future work will test whether these genes play a critical role in oocyte aging.
“Here we show that the final step of oocyte maturation itself might be negatively affected by age, which is critical for reproduction because it provides the material early embryos need to develop normally and survive,” says Bernhard Payer, AXA Professor of Risk prediction in age-related diseases and Group Leader at the Centre for Genomic Regulation (CRG) and co-author of the study. “What we don’t know yet, is which of these changes are merely a consequence of the aging process and which may directly contribute to the quality drop in oocytes with age.”
The researchers also used donor height and weight information to assess the impact of body mass index (BMI) on the transcriptome. Unlike age, abnormal BMI mostly affected the transcriptome of immature oocytes. According to the authors, the finding suggests that the fertility decline caused by age might have different root mechanisms than the one caused by abnormal BMI.
Women’s fertility generally declines with age. One of the main reasons for this is due to depleted ovarian reserves, as baby girls are born with all the oocytes, from which mature eggs will develop, during their lifetime. Another reason is that the quality of eggs lowers with age, which is thought to be one of the main reasons for higher rates of infertility after the age of 35. Being overweight or underweight has also been associated with poor oocyte quality and reproductive outcome.
The authors conclude that though more studies are required, their findings may result in the future development of new diagnostic tools to better assess oocyte quality in reproductive medicine, as well as potential drug treatments that modulate the affected pathways to rejuvenate aged oocytes.
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More sleep could offset children’s excess indulgence over the school holidays as new research from the University of South Australia shows that the same decline in body mass index may be achieved by either extra sleep or extra exercise.
The striking new finding is part of a study that shows how children can achieve equivalent physical and mental health benefits by choosing different activity trade-offs across the 24-hour day.
Conducted in partnership with the Murdoch Children’s Research Institute, and supported by the National Heart Foundation of Australia, the team examined the optimal balance between children’s physical activity, sleep, and sedentary time across the 24-hour day to better inform tailored lifestyle choices.
On a minute-for-minute basis, moderate-to-vigorous physical exercise was shown to be 2-6 times more potent than sleep or sedentary time.
While exercise has a greater and faster impact on physical health and wellbeing, children may be able to achieve the same 7.4% reduction in body mass index (BMI) by either: exercising 17 more minutes (moderate-to-vigorous exercise) OR sleeping an extra 52 minutes OR reducing their sitting or sedentary time by an extra 56 minutes.Similarly, children may significantly improve their mental health by either: exercising 35 minutes more (moderate-to-vigorous exercise), OR sleeping an extra 68 minutes OR reducing their sitting or sedentary time by 54 minutes.The study assessed 1179 children aged 11-12 years, from the cross-sectional Child Health CheckPoint Study. Physical wellbeing was measured via BMI, waist girth and body fat; mental wellbeing was measured via self-reported responses on the Paediatric Quality of Life Inventory.

Whether you hanker for a hard hit of caffeine or favour the frothiness of a milky cappuccino, your regular coffee order could be telling you more about your cardio health than you think.
In a world first study of 390,435 people, University of South Australia researchers found causal genetic evidence that cardio health — as reflected in blood pressure and heart rate — influences coffee consumption.
Conducted in partnership with the SAHMRI, the team found that people with high blood pressure, angina, and arrythmia were more likely to drink less coffee, decaffeinated coffee or avoid coffee altogether compared to those without such symptoms, and that this was based on genetics.
Lead researcher and Director of UniSA’s Australian Centre for Precision Health, Professor Elina Hyppönen says it’s a positive finding that shows our genetics actively regulate the amount of coffee we drink and protect us from consuming too much.
“People drink coffee for all sorts of reasons — as a pick me up when they’re feeling tired, because it tastes good, or simply because it’s part of their daily routine,” Prof Hyppönen says.
“But what we don’t recognise is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic a mechanism.

Social medicine programs, which often encourage patients to engage with other people, can help address dementia, isolation and more.This article is part of our new series on the Future of Health Care, which examines changes in the medical field.Less than five years ago, Mary Albrecht was a professor of marketing at Maryville University in St. Louis. She gave lectures and led classroom discussions; she advised students; she interacted with her faculty colleagues. In 2017, Ms. Albrecht learned she had Alzheimer’s disease, and she retired that same year — losing a network of students, colleagues and friends that had nourished her for 31 years.As her Alzheimer’s advanced, Ms. Albrecht found herself — despite the best efforts of her husband, Jack, and their children — increasingly isolated. Then in 2019 a social worker told Mr. Albrecht about a cognitive stimulation therapy group at Saint Louis University’s Aging and Memory Clinic. The group follows a treatment protocol designed to help engage patients with moderate-to-severe levels of Alzheimer’s and Lewy Body dementia. Ms. Albrecht, 70, who lives with her husband in the St. Louis suburb of Chesterfield, Mo., has now been taking part in the weekly sessions with around eight other dementia patients for about a year and a half.Ms. Albrecht is one of 144 participants in the clinic’s 12 groups, which are funded by a research grant so there is no cost to the patients. During the hourlong group sessions, at first in person but now remote during the pandemic, Ms. Albrecht and the other patients listen to music and participate in group discussions led by a moderator. These discussions vary depending on the level of impairment and include topics such as what animals patients like at the zoo and what movies they’ve seen. The goal is to improve various aspects of cognition and memory in a stimulating, positive social environment where patients engage with one another.“The interaction,” said Mr. Albrecht, an engineer who retired last year from a career in the energy conservation field to help take care of his wife, “that’s the main benefit we see for Mary.”“She’s always been a people person,” he added. “So, this is really great for her.”She’s not alone. “Like all human beings, people with dementia continue to need social interaction,” said Aimee Spector, a professor of old age clinical psychology at University College London, who created the cognitive-stimulation program that the Saint Louis University group is based on. Although the program was originally designed to allow patients to interact in groups or one-on-one, “we’ve found that cognition and quality of life seems to improve significantly when they’re in a group.”As such, the program is an example of what may become part of the treatment for a wide range of issues: socialization, or, as it’s often being described, “a social prescription.”This is not just a case of physicians encouraging their patients to get out and see friends a little bit more. Social medicine is more systematic and often involves the use of structured group interactions.“I think it’s the way of the future,” said the U.C.L.A. neurologist Indu Subramanian, director of the Department of Veterans Affairs Southwest Parkinson’s Disease Research, Education and Clinical Center. “Social prescribing meets people in the community where they are, and links them to social support structures.”Dr. Subramanian said she had seen the value of social group interactions for her Parkinson’s patients: “Loneliness is a big issue for them. Any way we can develop connections can help.”Social prescriptions are already being written in Britain, where physicians can now direct patients to a “link worker,” a trained specialist who focuses on connecting patients to community groups and services for practical and emotional support. Link workers not only connect patients with existing groups but also help create new groups, working as needed with local partners.Britain’s National Health Service calls social prescribing a “key component” of the country’s health care system, and it has set a goal to have nearly one million patients referred for social-prescription interventions by 2024.“It’s now part of normal practice,” said Dr. Krishna Kasaraneni, a general practitioner in the Yorkshire city of Sheffield, and a member of the British Medical Association executive committee that helped lead the effort to implement social prescribing in 2019. “We use it for vulnerable older patients who live by themselves, for people with diabetes who are overweight, and we put them in touch with community groups that can help get them outside and exercising.”And, he added, it’s not just older adults who benefit. “I have young patients with other chronic conditions, people with mental health issues,” he said. “There are no age barriers, no limits on what social prescribing can support people with.”A social prescription may involve helping patients to get outside and exercise.Sean Gallup/Getty ImagesThat view appears to be shared by a growing number of individuals and organizations in the United States, including Surgeon General Vivek H. Murthy, who in his 2020 book “Together: The Healing Power of Human Connection in a Sometimes Lonely World,” wrote that social prescribing “reflects a recognition that loneliness affects our health, and we have a universal need to connect with one another.”Last year, the V.A. started “a new social prescription program,” called Compassionate Contact Corps. Originally a home visitation program, it was restarted as a teleservice for veterans experiencing loneliness and social isolation when the pandemic hit. About 1,000 veterans are participating in the program, which involves phone or video calls with trained volunteers and requires a referral from the veteran’s medical care team.“Veterans we weren’t able to reach with the in-home program, we are able to reach with the ‘phone buddy’ program,” said Prince Taylor, deputy director for the V.A.’s Center for Development and Civic Engagement. “Overwhelmingly, the veterans who have participated in this program tell us it is helping them.”But how, exactly? And can the outcomes of social prescribing be accurately measured? “I would not have any hesitation saying that socialization is an important aspect of health,” said the Cleveland Clinic neurologist Marwan Sabbagh, director of translational research at the clinic’s Lou Ruvo Center for Brain Health in Las Vegas. “But the quantification is something that needs to be done in a way that would be universally accepted. We can measure things like memory and cognition, but I’m not familiar with ways we can clinically capture or quantify social isolation.”He added that researchers in other disciplines — the social sciences, for example — might have tools to help with this and could play a role in the future of developing social prescription protocols in the United States.The authors of a recent New England Journal of Medicine article on the British social prescription model agree that better assessment methods are needed. While calling the implications of social prescribing “profound,” they noted that “physicians need reliable information on what interventions work best and for whom and how social prescription can best be integrated into conventional medical practice.”Some see this as linked to a larger shift in medicine toward a more holistic approach. “We have to remember,” said Dr. Kasaraneni, “people don’t come to us with a list of medical problems; they come with a life, and a life that may have medical issues but also social and emotional issues.”Other doctors say that social prescribing may become the norm in the United States sooner than later. “I think the pandemic has really opened up the door for this kind of thing,” said Dr. Malissa J. Wood, co-director of the Corrigan Women’s Heart Health Program at the Massachusetts General Hospital Heart Center. Dr. Wood has used structured support groups as part of community programs she designed to improve the cardiovascular health of low-income, high-risk women.“I think this will definitely become more of a structured part of the practice of medicine,” she said. “People recognize that it’s not that hard to log on to a virtual group meeting, and it can bring people together who wouldn’t have otherwise been able to.”That’s how Mr. Albrecht said he felt about his wife’s weekly group sessions at the Saint Louis University program. And his criterion for assessing its value is simple. “Any time she gets that social interaction, the smile is there,” he said. “I wish she could do it every day.”

Physical activity during pregnancy might have long-lasting benefits for a child’s health, new research suggests.The lifestyles of soon-to-be mothers and fathers could shape the health of their unborn offspring in lasting ways, according to a surprising new animal study of exercise, diet, genetics and parenthood.The study found that rodent parents-to-be that fatten on a greasy diet before mating produce offspring with sky-high later risks for metabolic problems. But if the mothers stay active during their pregnancies, those risks disappear.The study involved mice, not people, but does suggest that when a mother exercises during pregnancy, she may help protect her unborn children against the unhealthy effects of their father’s poor eating habits, as well as her own. The findings add to our growing understanding of the ways in which parents influence children’s long-term health, even before birth, and suggest how physical activity during pregnancy might help to ensure that those impacts are beneficial.Researchers have known for some time that parents, and especially mothers, begin influencing the health and behavior of their offspring well before conception. Studies involving both animals and people show that mothers with diabetes, obesity, insulin resistance or other metabolic problems before pregnancy tend to have babies with a predisposition to those same conditions as adults, even if the offspring follow healthy lifestyles. Mothers who are lean and physically active during pregnancy, meanwhile, tend to have children who, as adults, are active and metabolically healthy.A hefty percentage of these differences are a result, no doubt, of nurture, since children readily adopt the diet and exercise habits of their parents. But some proportion of babies’ metabolic futures seem hard-wired, built into them as they develop in the womb, through a process that scientists call metabolic programming.Metabolic programming is complex and still only partially understood, but involves the inner workings both of the womb and of parental DNA. Some aspects of the environment inside the womb can change, depending on a mother’s health and lifestyle, affecting the development of organs and biological systems in the fetus.Ditto for parental genetics. The operations of certain of our genes shift in response to our diets, exercise habits, metabolic health and other lifestyle factors. These shifts, which are known as epigenetic changes, become embedded in our DNA and can be passed along to the next generation by mothers or fathers.In this way, metabolic problems can be inherited, propagating across generations.But there are hints that physical activity snips this cycle. In past rodent studies, if the soon-to-be parents ran before mating, they typically produced offspring without heightened risks for diabetes or obesity, even if the parents themselves experienced those conditions.Most of these studies focused their attention on the impacts of the mothers’ health and habits, though. Less has been known about how a father’s metabolic health changes his children’s long-term metabolic prospects and whether a mother’s activities during pregnancy might counter any negative outcomes from a father’s way of life.So, for the new study, which was published in March in the Journal of Applied Physiology, scientists at the University of Virginia School of Medicine and other institutions first gathered a large group of mice. Some of the animals, male and female, were allowed to gorge on a high-fat, high-calorie diet, inducing obesity and metabolic problems, while others remained on normal chow, at their usual weight.Next, the mice hooked up, with obese animals of both genders mating with normal-weight mice, so that, in theory, one parent in each pairing could bequeath unhealthy habits and metabolism to the young. A few normal-weight animals without metabolic problems also mated, to produce control offspring.Finally, some mothers, including the obese, jogged on little running wheels throughout the resulting pregnancies, voluntarily covering up to seven miles a week in the early stages of their three-week gestations.Afterward, the researchers tracked the metabolic health and underlying genetic activity of the offspring, until they reached adulthood. This second generation ate normal chow and led normal, lab-mouse lives.Many, though, developed multiple metabolic problems as adults, including obesity, insulin resistance and other disruptions of their blood-sugar control. These conditions were most pronounced in the male children of obese mothers and in both the male and female children born to obese fathers.Interestingly, the underlying genetics of their conditions differed by parental gender. Mice born to obese mothers displayed unusual activity in a set of genes known to be involved in inflammation. Those born to obese fathers did not.In other words, the genetic legacies from mothers and fathers “operate through different biological pathways,” says Zhen Yan, a professor of medicine and director of the Center for Skeletal Muscle Research at the University of Virginia School of Medicine, who oversaw the new study.Perhaps most important, though, when the mothers ran during pregnancy, their children showed almost no undesirable metabolic outcomes as adults, whether the mother or father was obese. These offspring, metabolically and genetically, remained indistinguishable from animals born to healthy parents.Of course, this was a rodent study and we are not mice, so it is impossible to know if we — as mothers, fathers or offspring — respond similarly to diets and exercise, or if the effects are amplified when both parents are affected. The study also does not show if it is obesity or a high-fat diet that most drives intergenerational harms or what the ideal timing, types and amounts of exercise might be by either mom or dad, to combat those effects.Dr. Yan says he and his colleagues plan to investigate those questions in future experiments. But already, the current study and other research suggest, he says, that physical activity, before and during pregnancy, and by both the expectant mother and father, “should absolutely be encouraged.”

Here’s what parents need to know.As a psychologist who cares for adolescents I am well aware of the prevalence of eating disorders among teenagers. Even still, I am stunned by how much worse the situation has become in the pandemic.According to the psychologist Erin Accurso, the clinical director of the eating disorders program at University of California, San Francisco, “our inpatient unit has exploded in the past year,” taking in more than twice as many adolescent patients as it did before the pandemic. Dr. Accurso explained that outpatient services are similarly overwhelmed: “Providers aren’t taking new clients, or have wait-lists up to six months.”The demand for eating disorder treatment “is way outstretching the capacity to address it,” said the epidemiologist S. Bryn Austin, a professor at the T.H. Chan School of Public Health and research scientist in the Division of Adolescent and Young Adult Medicine at Boston Children’s Hospital. “I’m hearing this from colleagues all across the country.” Even hotlines are swamped. The National Eating Disorders Association helpline has had a 40 percent jump in overall call volume since March 2020. Among callers who shared their age over the last year, 35 percent were 13 to 17 years old, up from 30 percent in the year before the pandemic.What has changed in the pandemic?There are several possible explanations for this tsunami of eating concerns in teenagers. When adolescents lost the familiar rhythm of the school day and were distanced from the support of their friends, “many of the things that structured a teenager’s life evaporated in one fell swoop,” said Dr. Walter Kaye, a psychiatrist and the founder and executive director of the eating disorders program at University of California, San Diego. “People who end up with eating disorders tend to be anxious and stress sensitive — they don’t do well with uncertainty.”Further, eating disorders have long been linked with high achievement. Driven adolescents who might have normally poured their energy into their academic, athletic or extracurricular pursuits suddenly had too much time on their hands. “Some kids turned their attention toward physical health or appearance as a way to cope with anxiety or feel productive,” Dr. Accurso said. “Their goals around ‘healthy’ eating or getting ‘in shape’ got out of hand” and quickly caused significant weight loss.For some, an increase in emotional eating in the pandemic has been part of the problem. Attending school from a home where food is constantly available may lead some young people to eat more than usual as a way to manage pandemic-related boredom or stress. “Being at school presents a barrier to using food as a coping mechanism; at home, we don’t have that barrier,” noted Kelly Bhatnagar, psychologist and co-founder of the Center for Emotional Wellness in Beachwood, Ohio, a practice specializing in the treatment of eating disorders.In many households the pandemic has heightened food insecurity and its attendant anxieties, which can increase the risk of eating disorders. Research shows that, compared to teenagers whose families have enough food, those in homes where food is scarce are more likely to fast, to skip meals, and to abuse laxatives and diuretics with the aim of controlling their weight.The Instagram influenceWhat teens see on their screens is also a factor. During the pandemic, teenagers have spent more time than usual on social media. While that can be a source of much needed connection and comfort, scrutinizing images of peers and influencers on highly visual social media has been implicated in body dissatisfaction and disordered eating. Dr. Austin noted that teenagers can be prone to comparing their own bodies to the images they see online. “That comparison creates a downward spiral in terms of body image and self-esteem. It makes them more likely to adopt unhealthy weight control behaviors.”When adolescents take an interest in managing their weight, they often go looking for guidance online. Indeed, a new Common Sense Media survey found that among teenagers who sought health information online between September and November of 2020, searches on fitness and exercise information came second only to searches for content related to Covid-19 — and ahead of searches on anxiety, stress and depression.What young people find when they go looking for fitness information can be highly problematic. They are likely to come across harmful “thinspiration” and “fitspiration” posts celebrating slim or sculpted bodies, or even sites that encourage eating disordered behavior. Worse, algorithms record online search information and are “deliberately designed to feed harmful weight loss content to users who are already struggling with body image,” such as advertisements for dangerous diet supplements, Dr. Austin said.When to worryWith so many forces contributing to teenagers’ body dissatisfaction and eating disordered behavior, how do parents know when to worry?Parents should be alarmed, Dr. Kaye said, “if your child suddenly loses 10 to 20 pounds, becomes secretive about eating, or if you are seeing food disappear,” as becoming furtive about what, how and when one eats is a common occurrence in anorexia, bulimia and other eating disorders.Experts agree that adults should be on the lookout for behaviors that veer from previous norms, such as suddenly skipping family meals or refusing to eat food from entire categories, such as carbohydrates or processed foods. Worth concern, too, is the teenager who develops fixations such as carefully counting calories, exercising obsessively or hoarding food, which may be a sign of a binge eating disorder. Parents should also pay close attention, said Dr. Accurso, if adolescents express a lot of guilt or anxiety around food or eating, or feel unhappy or uncomfortable with their bodies.According to Dr. Bhatnagar, the view of eating disorders as a “white girls’ illness” can keep teens who are not white girls from seeking help or being properly screened for eating disorders by health professionals, even though eating disorders regularly occur across both sexes and all ethnic groups.“Boys are having the same troubles,” said Dr. Bhatnagar, “but heterosexual boys may talk about body image a little differently. They tend to talk in terms of getting fit, getting lean or being muscular.”Dr. Austin also noted that it is common to see elevated rates of eating disorders in lesbian, gay and bisexual youth of all genders as well as transgender and gender diverse young people.“Eating disorders,” Dr. Accurso said, “don’t discriminate.”How to helpResearch shows that early identification and intervention play a key role in the successful treatment of eating disorders. Accordingly, parents who have questions about their teen’s relationship with eating, weight or exercise should not hesitate to seek an evaluation from their pediatrician or family health provider. Trustworthy eating disorder information, screening tools and support can also be found online. And when necessary, online resources can provide guidance and support to those on treatment waiting lists. “It may not be ideal for many,” Dr. Kaye said, “but it’s the reality of the situation we’re in.”Parents can also take steps to reduce the likelihood that an eating disorder will take hold in the first place. Experts encourage adults to model a balanced approach to eating and to create enjoyable opportunities for being physically active while steering clear of negative comments about their teenager’s body or their own. Parents should also openly address the dangers of a ubiquitous diet culture that emphasizes appearance over well-being, creates stigma and shame around weight and links body size to character and worth. As Dr. Accurso noted, “We are not defined by a number on a scale.”Where to find helpThe National Eating Disorders Association, or NEDA, is a good starting place. It supports individuals and families affected by eating disorders.F.E.A.S.T. is an international nonprofit organization run by caregivers of those suffering from eating disorders, meant to help others.Maudsley Parents was created by parents who helped their children recover with family-based treatment, to offer hope and help to other families confronting eating disorders.The Academy for Eating Disorders offers many resources, as do the Eating Disorders Center for Treatment and Research at University of California, San Diego, and the Eating Disorders Program at Boston Children’s Hospital.

Inside this facility in Chesterfield, Missouri, trillions of bacteria are producing tiny loops of DNA containing coronavirus genes — the […]