Caloric Restriction Could Mean a 20% Extension in Lifespan

Sinclair and several other prominent gerontologists are presently seeking human therapies based on the long-standing observation that lifelong restriction of caloric intake considerably extends both the healthy and total life span of nearly all species in which it has been tried, including rodents and dogs. Drugs that elicit the gene expression changes that result from caloric restriction might, these workers assert, extend human life span by something approaching the same proportion as seen in rodents—20% is often predicted—without impacting quality of life, and even when administered starting in middle age. They assiduously stress, however, that anything beyond this degree of life extension is inconceivable.

I agree with these predictions in two respects: that the degree of life extension achieved by first-generation drugs of this sort may well approach the (currently unknown) amount elicitable by caloric restriction itself in humans, and that it is unlikely to be much exceeded by later drugs that work the same way. In two other ways, however, I claim they are incorrect. The first error is the assumption of proportionality: I have recently argued (de Grey 2004), from evolutionary considerations, that longer-lived species will show a smaller maximal proportional life-span extension in response to starvation, probably not much more than the same absolute increase seen in shorter-lived species. The second error is the assertion that no other type of intervention can do better. In concert with other colleagues whose areas of expertise span the relevant fields, I have described (de Grey et al. 2002, 2004) a strategy built around the actual repair(not just retardation of accumulation) of age-related molecular and cellular damage—consisting of just seven major categories of ‘rejuvenation therapy’ (Table 1)—that appears technically feasible and, by its nature, is indefinitely extensible to greater life spans without recourse to further conceptual breakthroughs.