We don’t have any idea why we age, or actually we have lots of ideas; we just don’t know if any of them are correct. Almost thirty years ago, Zhores Medvedev, a Russian biogerontologist, counted some three hundred serious scientific theories to explain why we age, and the number has not shrunk in the decades since. As Professor José Viña and colleagues from the University of Valencia put it in a summary of current thinking, the theories fall into three broad categories: the genetic mutation theories (your genes malfunction and kill you), the wear-and-tear theories (the body just wears out), and the cellular waste accumulation theories (your cells clog up with toxic by-products). It may be that all three factors work together, or it may be that any two of the above are side effects of the third. Or it may be something else altogether. No one knows.
In 1961, Leonard Hayflick, then a young researcher at the Wistar Institute in Philadelphia, made a discovery that nearly everyone in his field found impossible to accept. He discovered that cultured human stem cells—that is, cells grown in a lab, as opposed to in a living body—can divide only about fifty times before they mysteriously lose their power to go on. In essence, they appear to be programmed to die of old age. The phenomenon became known as the Hayflick limit. It was a milestone moment for biology because it was the first time anyone had shown that aging was a process happening within cells. Hayflick also found that the cells he cultured could be frozen and kept in storage for any length of time and when thawed would resume their decline from precisely where they had left off. Clearly something within them was serving as a kind of tallying device to keep track of how many times they had divided. The idea that cells possess some form of memory and can count down toward their own extermination was so wildly radical that it was almost universally rejected.
For about a decade, Hayflick’s findings languished. But then a team of researchers at the University of California at San Francisco discovered that stretches of specialized DNA at the end of each chromosome called telomeres fulfill the role of tallying device. With each cell division, telomeres shorten until eventually they reach a predetermined length (which varies markedly from one cell type to another) and the cell dies or becomes inactive. With this finding, the Hayflick limit suddenly became credible. It was hailed as the secret of aging. Arrest the shortening of telomeres and you could stop cell aging in its tracks. Gerontologists everywhere became very excited.
Alas, years of subsequent research have shown that telomere shortening can account for only a small part of the process. After the age of sixty, the risk of death doubles every eight years. A study by geneticists at the University of Utah found that telomere length may account for as little as 4 percent of that additional risk. As the gerontologist Judith Campisi told Stat in 2017, “If all aging was due to telomeres, we would have solved the aging problem a long time ago.”
Aging, it turns out, not only involves much more than telomeres, but telomeres are involved in much more than aging. Telomere chemistry is regulated by an enzyme called telomerase, which switches off the cell when it has reached its preset quota of divisions. In cancerous cells, however, telomerase doesn’t instruct the cells to stop dividing, but rather lets them go on proliferating endlessly. This has raised the possibility that a way to fight cancer would be to target telomerase in the cells. In sum, it’s clear that telomeres are important not just for understanding aging but also for understanding cancer, but unfortunately we are still a long way from fully understanding either.
Two other terms encountered commonly, if no more productively, in discussions of aging are “free radicals” and “antioxidants.” Free radicals are wisps of cellular waste that build up in the body in the process of metabolism. They are a by-product of our breathing oxygen. As one toxicologist has put it, “The biochemical price of breathing is aging.” Antioxidants are molecules that neutralize free radicals, so the thinking is that if you take a lot of them in the form of supplements, you can counter the effects of aging. Unfortunately, there is no scientific evidence to support that.
Most of us would almost certainly never have heard of either free radicals or antioxidants if a research chemist in California named Denham Harman had not, in 1945, read an article about aging in his wife’s Ladies’ Home Journal and developed a theory that free radicals and antioxidants are at the heart of human aging. Harman’s idea was never anything more than a hunch, and subsequent research proved it to be wrong, but nonetheless the idea has taken hold and will not go away. The sale of antioxidant supplements alone is now worth well over $2 billion a year.
“It is a massive racket,” David Gems of University College London told Nature in 2015. “The reason the notion of oxidation and ageing hangs around is because it is perpetuated by people making money out of it.”
“Some studies have even suggested that antioxidant supplements can be harmful,” The New York Times has noted. The principal learned journal of the field, Antioxidants and Redox Signaling, noted in 2013 that “antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death.”
In the United States, there is the additional, rather extraordinary consideration that the Food and Drug Administration exercises practically no oversight on supplements. As long as supplements don’t contain any prescription medications and don’t obviously kill or seriously harm anybody, manufacturers can sell pretty much whatever they want, with “no guarantees of purity or potency, no established guidelines on dosage, and often no warnings about side effects that may result when the products are taken along with approved medications,” as an article in Scientific American noted. The products might be beneficial; it’s just that no one has to prove it.
Although Dr. Harman didn’t have anything to do with the supplements industry and was not a spokesman for antioxidant theories, he did follow a lifelong regime of taking high doses of the antioxidant vitamins C and E, and eating large quantities of antioxidant-rich fruits and vegetables, and it must be said it didn’t do him any harm at all. He lived to be ninety-eight.
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Even if you enjoy robust health, aging has inescapable consequences for us all. As we age, the bladder becomes less elastic and cannot hold as much, which is why one of the curses of aging is being forever on the lookout for a restroom. Skin loses elasticity, too, and becomes drier and more leathery. The blood vessels break more readily and create bruises. The immune system fails to detect intruders as reliably as it once did. The number of pigment cells usually decreases, but those that remain sometimes enlarge, producing age spots, or liver spots, which of course have nothing to do with the liver. The layer of fat directly associated with skin also thins, making it harder for elderly people to stay warm.
More seriously, the amount of blood pushed out with each heartbeat falls gradually as we age. If nothing else gets you first, your heart will eventually give out. That is a certainty. And because the amount of blood being moved around by the heart falls, your organs get less blood, too. After the age of forty, the volume of blood going to the kidneys decreases by an average of 1 percent a year.