Top banner


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.


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.

Why One Threat at a Time?

2011-07MacroGemsFB.jpgClick to Enlarge ImageThe realization that aging can be manipulated has profound implications for people. Controlled reduction of food intake (dietary restriction) can improve late-life health and increase lifespan in mammals, from rodents to rhesus monkeys. Whether it might do the same in humans is currently under investigation. One aim of aging research is to develop drugs that can reproduce the effects of dietary restriction and also of genetic alterations that slow aging. One approach could be to use drug therapy to target the nutrient-sensitive pathways that regulate aging (for example, TOR) and that seem to mediate the effects of dietary restriction on aging. The ultimate goal would be a pill that one could take regularly from midlife onward. This pill would theoretically slow aging with minimal side effects. Its predicted impact would be to reduce the incidence of aging-related disease at all ages—although not to remove them altogether. This would lengthen good health later into life and extend our lifespan—possibly without expanding periods of disability and dependency.

Such an approach could revolutionize the ways that diseases of aging are combated. Currently they are, by and large, tackled individually. One scientist studies heart disease, another Alzheimer’s disease, another macular degeneration and so on. Yet such ailments are symptoms of a larger underlying syndrome: aging. It is for this reason that there is a law of diminishing returns when it comes to treating diseases of aging. The battle with aging is akin to that between Heracles, the hero of Greek mythology, and the multiheaded Hydra. Each time Heracles hacked off a head, two more would sprout in its place. Likewise, the old man successfully treated for prostate cancer may not long afterward stagger back into the physician’s office with macular degeneration and dementia. Such piecemeal approaches to treating age-related illness have undoubtedly improved late-life health to an extent and they have increased life expectancy. This, again, is something to celebrate. Yet in the long run a more powerful way to protect against age-related disease would be to intervene in the aging process itself. This would provide protection against the full spectrum of age-related illnesses. Returning to our classical illustration, to really defeat the diseases of late life we need to strike at the heart of the Hydra of senescence: the aging process itself. But is this actually where biogerontology is headed?

After establishing my own research laboratory some years ago, I found myself brooding about the purpose of biogerontology. As a scientist working on aging, what exactly should I be trying to achieve? What was the big plan? I began asking other biogerontologists and soon discovered that there was no unified vision regarding what to do about aging once we understood it. I realized that I’d have to try to figure this out for myself. It helped that a few people had wondered about this before, particularly in medical ethics. In 2003 Eric Juengst at Case Western Reserve University identified three distinct goals for biogerontology. One he called compressed morbidity. This entails improving late-life health while avoiding any major extension of lifespan. Another was arrested aging, that is to say, stopping aging altogether. And the third was decelerated aging, slowing down the aging process. Putting aside the question of the pros and cons of each goal, only decelerated aging seemed plausible to me, given recent developments in biogerontology.


New Ethical Challenges




comments powered by Disqus


Bottom Banner