BETHESDA, September 21 — The science of longevity has moved a long way from a Cornell University laboratory where, in 1935, Clive McCay and his colleagues showed that simply feeding laboratory rats less food could extend how long they lived. It was the first demonstration that diet can alter the rate of aging in mammals, and it opened a question researchers are still chasing: how much of our lifespan is fixed, and how much can be changed?
Decades later, in the 1990s, Cynthia Kenyon’s lab at the University of California, San Francisco delivered an answer that startled the field. A single mutation in the daf-2 gene doubled the lifespan of the nematode Caenorhabditis elegans.
Aging, it turned out, was genetically regulated rather than fixed. That work led researchers to the insulin/IGF-1 signaling pathway and the TOR pathway, both now recognized as conserved longevity regulators across yeast, worms, flies, and mice.
What the biology has shown
In 2009, Elizabeth Blackburn, Carol Greider, and Jack Szostak received the Nobel Prize in Physiology or Medicine for discovering how chromosomes are protected by telomeres and the enzyme telomerase. Telomere length has since been studied as a marker of cellular aging. The National Institute on Aging, part of the US National Institutes of Health, was established in 1974 and funds much of the basic research on aging biology.
Human evidence comes from long-running cohort studies. The Baltimore Longitudinal Study of Aging, begun in 1958, is one of the longest-running studies of human aging.
The Framingham Heart Study, launched in 1948, identified smoking, high blood pressure, and high cholesterol as cardiovascular risk factors that shape lifespan. Research on so-called blue zones—regions such as Okinawa, Japan; Sardinia, Italy; Ikaria, Greece; Nicoya, Costa Rica; and Loma Linda, California—has documented clusters of centenarians. But scientists including Saul Newman have questioned data quality and age-verification in some of these populations.
Two studies have sharpened the debate over whether there is a hard ceiling on human life. In 2018, a study published in Science by researchers at Yale and other institutions found that the mortality rate in humans plateaus after age 105, with the risk of death leveling at about 50 percent per year.
In 2021, a study in Nature Communications led by researchers at the University of Göttingen estimated that the human lifespan may be limited to about 120 to 150 years, based on blood markers and physical activity data.
Drugs, companies, and what is not yet approved
Pharmacological approaches under study include rapamycin, an immunosuppressant approved by the US Food and Drug Administration in 1999 for transplant patients, which has extended lifespan in mice; metformin, a first-line diabetes drug; and senolytics, drugs that clear senescent cells. None of these has been approved by the FDA for anti-aging use in healthy humans. The FDA has stated that aging is not an approved indication for any drug.
Companies such as Calico, founded by Google in 2013, and Altos Labs, launched in 2022 with backing from investors including Jeff Bezos, are pursuing basic research on aging. For all the molecular promise, the lifestyle factors with the strongest human evidence remain regular physical activity, a diet rich in plants and low in processed foods, avoidance of smoking, moderate alcohol consumption, and adequate sleep.
The stakes are global. The World Health Organization projects that the number of people aged 60 and older will double by 2050, reaching 2.1 billion, making healthy aging a global public health priority. What to watch next: whether any of the drugs now under study clears the FDA’s bar for healthy aging, and whether the cohort studies and blue-zone data can settle the question of how long a human life can run. Consult your doctor for medical advice.
