Sci. Aging Knowl. Environ., 29 June 2005
Will We Find Biomarkers of Aging?
Science's 125th anniversary special issue
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2005/26/nf48
Because aging takes a lifetime to study, answers about it can be slow in coming. Scientists have to wait for an organism to die to gain insight into its demise. Moreover, that requirement renders the study of aging in humans--and tests of interventions that might retard it--nearly impossible. However, physiological or molecular measures besides life span that would provide a more practical indicator of aging might exist (see Miller Perspective). Can we find such biomarkers?
Officials at the National Institutes of Health thought so in 1988, when they initiated a 10-year program to identify biomarkers of aging in mice. But the project failed to identify clear winners. That outcome engendered pessimism about biomarkers' potential, but scientists have continued the search for them.
The first challenge is defining a useful biomarker. Opinions vary, but some general principles emerge. A biomarker should reflect the underlying aging process rather than disease. It should vary as an individual ages, but not strictly chronologically; instead, its quantity should correlate with remaining life span and with the likelihood of acquiring multiple age-related conditions, such as cataracts or stiff arteries. The characteristic should be easily measured: Invasive procedures that complicate data collection or that compromise an individual's health would kill a biomarker's utility. And to facilitate validation of a biomarker's power, it should apply to at least several species.
Researchers have identified some potential candidates. For instance, hormone quantities, shifts in amounts of particular types of immune cells, concentrations of a tumor-suppressor protein, and lengths of telomeres--protective caps on the ends of chromosomes--are statistically associated with the mortality of an individual (see Dimri Perspective, Rikke Perspective, and "When Tips Disappear, the End Is Near"). Calorie restriction--a reduction in calorie intake that extends longevity in numerous species--slashes insulin concentration and cools body temperature in rodents and rhesus monkeys; both measures normally rise with age. Researchers have found that longer-lived people also tend to have abnormally small amounts of insulin and low body temperatures; moreover, they have elevated quantities of the hormone DHEAS, also matching the trend observed in dieting monkeys (see "Monkey in the Middle"). But none of the contenders has yet proven its mettle as a biomarker. For instance, many of these measures vary widely among individuals, independent of age or health. This spread clouds the potential link to biological age.
Some experts say that suitable biomarkers will eventually emerge--provided researchers screen sufficiently large numbers of subjects to compensate for the variation. But don't expect to get tested someday for such benchmarks at your doctor's office: Because of variability, they probably would not be useful for accurately determining how long an individual would live. The effort, however, might provide biomarkers for rapidly assessing the biological age of a population, which would help test whether a genetic change or a pharmaceutical treatment postponed aging.
In addition to random variation, other factors might complicate the use of biomarkers in screening humans. For instance, a particular biomarker might prove most powerful in people with a certain genetic makeup or environmental exposure: Marker X might reflect aging well in meat-eating smokers but not in vegetarian marathon runners. In addition, different organs within the body might decay at different rates, requiring unique biomarkers for distinct tissues. Still, if a central "aging clock" paces the decay of an entire creature, as some experts postulate, biomarkers that maintain stride with that clock would represent the ultimate timer for aging. Ultimately, scientists will likely need a set of numerous biomarkers--perhaps some that provide a window on particular tissues and others that give a glimpse of an entire organism--to replace life span as the best measure of aging. If researchers can uncover measures that fit the bill, the discovery could speed efforts to slow aging.
June 29, 2005 Citation: R. J. Davenport, Will We Find Biomarkers of Aging? Sci. Aging Knowl. Environ. 2005 (26), nf48 (2005).
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