Sci. Aging Knowl. Environ., 19 December 2001
Vol. 2001, Issue 12, p. vp7
[DOI: 10.1126/sageke.2001.12.vp7]


Is Life-Span the Best Measure of Aging?

Douglas Crawford

The author is in the Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-0448, USA. E-mail: dcrawfo{at};2001/12/vp7

Key Words: gerontology • life-span • longevity assurance genes • longevity genes • biomarker

Aging is like pornography in that (and maybe only in that) you can't define it, but you sure do know it when you see it. Gerontologists have battled for years to find a suitable definition of aging; to date, the only quality that has remained universal and inseparable from aging is a progressive and irreversible increase in mortality. Thus, in order to predict how much longer an animal will live, the best information we have is its age.

But even age is a poor predictor at best. For instance, isogenic Caenorhabditis elegans raised in identical environments have life-spans that vary by a factor of 3. Furthermore, we'd like to know something about the quality of life and not just the probability of death. Aging can be described in terms of diminished capacity, and it is tragically true that some individuals live in a decrepit state for years. We are left then with the nagging doubt that biologists who study mortality as a function of time may not be studying "aging," because if they were, they would be able to provide both better predictions of life-span and better descriptions of the aging process at the molecular level.

Scientists have been trying to solve the problem of defining aging by searching for biomarkers of aging (see Miller Perspective). Such biomarkers would be traits that scale with life-span. Ideally, one could measure some attribute of an individual that would better predict their probability of death than does their age. The National Institute on Aging, for instance, has been encouraging the study of biomarkers since 1987, mostly through the use of calorically restricted rats. Identifying true biomarkers of aging will enable researchers to focus their attention on several interesting but currently frustrating areas of research, such as mutations that result in short-lived animals and aging in long-lived model organisms. In addition, biomarkers can aid in the identification of the salient causes of aging. When researchers find genetic and environmental changes that result in the extension of life-span, the results can be accepted without caveat as affecting processes that control longevity. However, the identification of genes that shorten life-span is problematic. How can we differentiate genes that cause disease from those that accelerate aging? Well, an excellent way to proceed would be to identify biological processes that scale with life-span and to ask whether these processes occur more quickly in a given mutant or under a given set of conditions. And for those brave souls who have taken up the study of aging in longer-lived species such as monkeys and humans, the use of biomarkers is essential. A researcher can hardly wait 40 to 60 years to determine whether caloric restriction, for example, extends the life-span of primates; rather, these scientists must make numerous physiological measurements along the way.

But even if we do find processes that scale with life-span, a further difficulty will be to identify the causes of aging as separate from its consequences. Is gray hair a cause or consequence of aging? What about dementia? For instance, we find that Jeanne Calment apparently retained her rather sharp wits until she died at 122. (She is reported to have said, "I have only one wrinkle, and I am sitting on it.") But she did age like everyone else (whatever that might mean). So we may be forced to drop, or at least more carefully define, mental decay as a fundamental part of aging.

The past decade has seen remarkable advances in our understanding of the mechanisms that control the life-spans of worms and yeast. These advances came in part from temporarily ignoring the common wisdom that aging is a quantitative trait that would be difficult to study using traditional genetics. By focusing on the irrefutable case of single-gene mutations that confer a substantial increase in life-span, great progress has been made. And by no means has the molecular genetic approach been exhausted. Thus, we have an example of how studying mortality, as opposed to aging itself, can give us great insight into the latter.

December 19, 2001 Citation: D. Crawford, Is Life-Span the Best Measure of Aging? Science's SAGE KE (19 December 2001),;2001/12/vp7

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