In yet another of its tedious campaigns, the World Health Organization established in 2021 that by 2030 it would be the Decade of Healthy Aging. Prolonging life without problems is the dream of gerontologists. But so far no one has reached 122 years of age. Is it possible to overcome this biological limit?
The aging of the world’s population is already becoming one of the greatest challenges of the 21st century: by 2050, one in five people will be over 60 years old. Increasing life expectancy is a success of human progress. Yet the vital advances of the last century are slowing. Now, the goal is to grow old without many problems.
In the year 2000, Steven Austad, then a professor at the University of Idaho, bet $150 that someone born that year would not only live to celebrate their 150th birthday, but would also be mentally sound. University of Chicago professor S. Jay Olshansky took the bet arguing otherwise. In 2016, both scientists doubled their bets. The winner will be determined in 2150: the money, with interest, will be received by the winner’s descendants, or even by Steven Austad himself, if he is still alive.
Prolonging life to the maximum without major deterioration, and without hibernation, of course, has been the greatest dream of human beings. Like Brandon Milholland, from the pharmaceutical research multinational IQVIA, and Jan Vijg, from Albert Einstein College of Medicine of New York, commented two years ago in the magazine Nature Aging, these desires were reflected in the immortal gods and were inspired by very long-lived legendary people, such as Noah or Methuselah. Mortality was a divine punishment.
The German biologist August Weismann, at the end of the 19th century, thought, in a more evolutionary way, that aging was programmed so that older people could give way to younger people. Once reproduced, they had no biological meaning. The fact is that to date no basis for an evolutionary advantage of aging has been identified. Some call it benign evolutionary neglect, whatever that means.
An insurmountable limit
Current scientific evidence indicates that breaking the biological limits of human life — 120 to 130 years — is impossible. Advances in healthy life expectancy were spectacular between the 1940s and 1980s, but began to show diminishing returns as early as the 1990s. Thus, in the 1950s, the oldest person recorded was 113 years old at the time of their death; In 1997, Frenchwoman Jeanne Calment broke the longevity record by reaching 122 years and 164 days, blind and deaf, but lucid. Since then, despite the huge increase in super seniors, progress has stagnated. No other documented person has lived past the age of 120.
Global life expectancy at birth and age 65 has increased from 47 and 76 years in 1950 to 73 and 82 years today, and is predicted to reach 77 and 84 years in 2050, not much beyond that. In other words, the advances of the last century, thanks to public health, food safety, vaccines, antibiotics and medical care, have mainly caused a huge reduction in infant mortality — which fell from 200 per 1,000 live births in the middle of the 19th century to less than 10 per 1,000 today — and a gradual increase in life expectancy, which is slowing. And there are cyclical factors, such as the opioid (fentanyl) crisis in the United States, wars or the coronavirus pandemic, which stagnate or reduce this increase.
Aside from breaking records — only one in every 100,000 people will live past 110 — the current goal is to achieve healthy longevity. At least that is the intention of the Decade of Healthy Aging (2021-2030), established by the World Health Organization in another of its campaigns, more theoretical than practical, that keep its employees busy. For the WHO, healthy aging means developing and maintaining, at advanced ages, the functional capacity — physical and mental — that enables well-being.
And how is that done? Very simple: Mediterranean or Japanese diet — places where life expectancy is higher —; exercise — at least half an hour a day —; two liters of water per day; eight hours of restful sleep; no toxins at work, at home, in the environment or addictions; constant brain activity — sudoku, languages and puzzles; Radiation-proof cockroach-like genetics, and a lot of luck.
Mechanisms of human expiry
As a precaution, some gerontologists and transhumanists, not convinced that there is a biological limit to death, avidly investigate to understand the mechanisms of human demise. They were euphoric when, in the nineties of the last century, it was demonstrated that in the nematode worm Caenorhabditis elegans — a classic research model — a single genetic mutation doubled your natural lifespan, specifically the insulin growth factor (IGF1) signal transduction pathway. Hence why many longevity researchers have decided to take metformin, a well-known antidiabetic drug. Rapamycin, an inhibitor of the mTOR protein, involved in cancer and aging and used against transplant rejection, is another of his favorite drugs.
Since then, new biomarkers, mutations and protective genes that extend the life of worms, flies and mice have been discovered. There are also promising trials with calorie restriction in monkeys: they coincide with the paradoxical observations of healthier societies after periods of famine or economic crises, as long as they are reversible. Overeating and food junk, on the other hand, accelerate inflammation and molecular oxidation, two conditions of rapid cellular wear. Other factors involved in biological aging are the shortening of telomeres — the ends of chromosomes —, DNA methylation and immunosenescence, a “wrinkled” immune system that brings infections and tumors.
Once retirement is reached and harmful habits — alcohol and tobacco, obesity, sedentary lifestyle and poor diet — have been avoided, instead of living 73 years, one can aspire to live 83, a decade longer. Crossing this threshold appears to depend primarily on individual genetics and a modern healthcare system.
Billionaires in search of “immortality”
The most recent advances have been mediated by improvements in the treatment of specific conditions. But the fundamental biology of aging has not changed, which has led to an exhaustion of options to continue improving. Despite promising molecular manipulations in worms, it has not been possible to increase the maximum lifespan of vertebrates.
“Our organism — Milholland and Vijg summarize — is a dynamic system, in a state of degradation and permanent repair. Aging means a disruption of this balance, when the accumulation of damage exceeds the capacity for repair. In the process, very varied factors intervene: influences genetic, behavioral and environmental, which could influence positively or negatively on each side of the scale”.
Breaking this biological limit, a recurring theme in science fiction, is the objective of some companies driven by billionaires in search of earthly immortality. The Methuselah Foundation, for example, created a series of awards to research longevity in rats; the SENS Foundation funds studies on aging and rejuvenation; Calico, a Google subsidiary, collaborates with universities and pharmaceutical laboratories; The Human Longevity, founded by geneticist Craig Venter, decoder of the human genome, advises on longevity genetics; The Altos Labs, owned by Jeff Bezos, owner of Amazon, has US$3 billion for scientific research; and the Foundation Hevolutioncreated by the Saudi Arabian royal family, plans to spend US$1 billion a year finding ways to slow down aging.
Everyone is trying to leverage some of the latest tools in biomedicine: CRISPR, artificial intelligence, Yamanaka factors, epigenetics, proteomics, metabolomics, etc. However, if in simple organisms, such as fruit flies, the gain was an extension of 60 to 100 days of life, which is not bad at all, mastering the immensity of human biological factors is presumably Promethean. And trying to imitate evolution and the mechanisms that made turtles or whales long-lived, which involves millions of genetic variants, becomes an impossible quest.
Live longer or live better?
A year and a half ago, science writer Jonathan Weiner, in an analysis of the search for eternal youth in Technology Review, concluded that, ultimately, older people “just want help to alleviate their osteoarthritis, their chronic kidney disease, their macular degeneration, their tumors, their deafness, their dementia, their diabetes and their osteoporosis.” The goal should be to “add good years to our lives without adding to the number of bad years at the end.”
And in a scenario where, at the end of the Decade of Healthy Aging (2030), the number of people aged 60 and over will have increased by 34% — from 1 billion in 2019 to 1.4 billion, and will be 2.1 billion in 2050 (one in every five people) —, with the costs and strain that this implies, this objective should be a priority.
We all aspire to a long life. But, programmed or not, aging, with its pains and afflictions, prepares us for death. Our ingrained survival instinct has difficulty recognizing, as so many philosophize, that the important thing is not how long you live, but how you live, and that a life well lived is worth it.
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