Invited commentry on ‘The aging feline kidney: A model mortality antagonist?’

In the special (pages 363–371 of this issue) ‘New Perspectives’ feature by Lawler et al (2006) some ideas not often considered in clinical veterinary journals are presented. In a recent elegant and accessible review, Gavrilov and Gavrilova (2002) enlighten us that while theories of aging have long history, the logical foundations for modern evolutionary theories of aging were completed only in the 1950s. At present the most viable evolutionary theories are the ‘mutation accumulation’ theory and the ‘antagonistic pleiotropy’ theory, which are not mutually exclusive.

The Lawler et al (2006) paper concludes from the presented data that the kidney lesions they observed may have evolved to preserve fertile reproductive life through the elimination of dysfunctional renal tubular cells and nephrons, although the underlying explanation(s) for this phenomenon are not presently evident. This hypothesis appears to represent an example of the antagonistic pleiotropy theory, which is based on the two assumptions that (1) a particular gene may have an effect on several traits of an organism (pleiotropy), and (2) that these pleiotropic effects may affect individual fitness in opposite (antagonistic) ways (Gavrilov and Gavrilova 2002).

Although this is a reasonable hypothesis, it is not the only one. For example, as only animals that died were evaluated, one cannot know the extent, severity and distribution of lesions in the animals that did not die. Because only a limited number of organs were evaluated, it is possible that some unidentified lesion was exerting undocumented effects. It may be that the lesions identified were more benign than the other causes of death, and so less likely to be lethal (rather than antagonistic). Excluding the role of variable combinations of these (and other) alternative explanations will be a daunting task for the investigators (Platt 1964).

Despite these possible limitations of the study, the authors raise a number of provocative issues, and are encouraged to mold them into testable hypotheses. Aging is a phenomenon that affects us from the moment of birth until the instant of death, and theories of the underlying mechanism(s) have a long and fascinating history. In a 2000 review, Guarente and Kenyon (2000) concluded that:

‘The field of ageing research has been completely transformed in the past decade…. When single genes are changed, animals that should be old stay young. In humans, these mutants would be analogous to a 90 year old who looks and feels 45. On this basis we begin to think of aging as a disease that can be cured, or at least postponed…. The field of aging is beginning to explode, because so many are so excited about the prospect of searching for — and finding — the causes of aging, and maybe even the fountain of youth itself.’

Our fascination with aging thus appears forever young, even if we are not.