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Aging: To Treat, or Not to Treat?

The possibility of treating aging is not just an idle fantasy

David Gems

Is Aging a Disease?

One argument against treating aging is that it is not a disease. To an extent, this view stems from the fact that the word aging refers to different things. One is the experience of the passage of time. Another is the acquisition of experience and wisdom that can come from living long. To avoid confusion with these benign aspects, biologists use the term “senescence” for the increasing frailty and risk of disease and death that come with aging. Put more precisely, then, the question at hand is this: Is human senescence a disease?

One approach to defining illness has been to compare a given condition to good health. Is someone’s condition typical of a person of a given gender or age? For instance, the possession of ovaries is healthy for a woman, but not a man. Likewise, one might consider muscle wasting to indicate serious disease in a 20-year-old, but not a 90-year-old. Given that everyone who lives long enough will eventually experience senescence, I can appreciate the view that it is a normal condition and therefore not pathological. Still, from my perspective as someone working on the biological basis of aging, it is hard not to see it as a disease.

Senescence is a process involving dysfunction and deterioration at the molecular, cellular and physiological levels. This endemic malfunction causes diseases of aging. Even if one ages well, escaping the ravages of cancer or type II diabetes, one still dies in the end, and one dies of something. Moreover, in evolutionary terms, aging appears to serve no real purpose, meaning it does not contribute to evolutionary fitness. Why, then, has aging evolved? The main theory dates back to the 1930s and was developed by J. B. S. Haldane and, later, Peter Medawar—both of University College London—and by the American biologist George C. Williams of the State University of New York, Stony Brook. It argues that aging reflects the decline in the force of natural selection against mutations that exert harmful effects late in life. An inherited mutation causing severe pathology in childhood will reduce the chances of reproduction and so disappear from the population. By contrast, another mutation with similar effects—but which surfaces after a person’s reproductive years—is more likely to persist. Natural selection can even favor mutations that enhance fitness early in life but reduce late-life health. This is because the early-life effects of genes have much stronger effects on fitness. Consequently, populations accumulate mutations that exert harmful effects in late life, and the sum of these effects is aging. Here evolutionary biology delivers a grim message about the human condition: Aging is essentially a multifactor genetic disease. It differs from other genetic diseases only in that we all inherit it. This universality does not mean that aging is not a disease. Instead, it is a special sort of disease.

A different worry about redefining aging as a disease is that it would lead to stigmatization of the elderly. Perhaps, but the recognition of late-onset Alzheimer’s disease as a pathology created an ethical imperative for research to understand and treat the condition. One might expect the same to be true of aging. Such a redefinition would also help to counter the blight that is the wholesale swindling of the elderly by practitioners of so-called anti-aging medicine. In the United States, the Food and Drug Administration (FDA) assures the safety and efficacy of medical treatments. Yet because aging is not viewed as a disease, orally administered drugs marketed as treatments for aging (resveratrol, for example) are subject only to the much laxer FDA regulations that apply to dietary supplements. Redefining aging as a disease would not only energize research into treatments, it would shut down the snake-oil peddlers.

The possibility of treating aging is not just an idle fantasy. One of the most remarkable discoveries in biology in recent decades is one that surprisingly few people know about: It is possible to slow aging in laboratory animals. In fact, it is easy. Work in my own lab focuses on the tiny nematode worm Caenorhabditis elegans, which is widely used in genetic studies. Even under optimal culture conditions, these creatures age and die within two to three weeks. In the early 1980s the American geneticist Michael Klass first discovered that by altering their genes, one can slow aging in C. elegans. The result is that the worms live much longer and they remain youthful and healthy longer. The current record for enhancing C. elegans longevity is an astonishing tenfold increase in lifespan, produced by a group at the University of Arkansas. It has now been shown that genes that influence aging in the worms also influence aging in mammals (in mice, to be precise). Humans also carry these genes.

By identifying genes that control aging rates, we can also learn about the underlying biology of aging. We can explore the aging-related processes that the genes influence. Many aging genes are associated with a nutrient-sensitive signalling network that includes insulinlike growth factor 1 (IGF-1) and an intracellular protein called TOR. Dampening the signals that this network transmits slows growth, increases resistance to stress and increases lifespan. Work in my laboratory and others at the Institute of Healthy Ageing in University College London aims to understand how exactly this network works to control aging. Answering this involves addressing the big question: What produces aging? One theory attributes it to an accumulation of molecular damage. Another points to excess biosynthesis; many genes and pathways that influence aging are associated with control of biosynthesis and growth. Yet the truth remains unclear.

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