Diverse aging rates in metazoans: targets for functional genomics.

Aging, or senescence, has typically been measured by demographic analysis, which has its merits but is blind to key aspects of functional development and deterioration. If one uses demographic analyses, however, the approach providing most insight is the analysis of age-specific mortality. The continuing increase in DNA sequencing power combined with emerging computational techniques will allow in the near future detailed investigation of mechanisms of aging in diverse species beyond the typical laboratory bestiary. A comparative approach of this sort needs to consider, in addition to simple longevity, the effects of phylogeny and body size on the species in question. Insight may be gained from the study of species exhibiting accelerated aging relative to more "typical" species. These naturally short-lived species, such as several small shrews and marsupials, avoid the worry inherent in "accelerated aging" genotypes of common models, which is that they are only short-lived because of some idiosyncratic pathology unrelated to general aging. A case of special interest that has yet to be seriously investigated is the domestic dog, in which selective breeding has produced phenotypes within the same species that age at two-fold different rates. Exceptionally long-lived species offer exceptional opportunities to discover whether there are few or many ways to create long-lived organisms. Slow-aging species with the most to offer include bats and naked mole-rats. Perhaps no fundamental question in biology is more intriguing that why and how nature has produced such a dazzling array of aging rates. The development of functional genetics over the next several decades promises to lead us toward an answer.