Listening to Resveratrol
Could the famous ingredient of red wine herald a new era in medicine?
There are many who would argue that significant extension of the human lifespan remains a pipe dream. Aging, they argue, is an over-determined process of cellular entropy, a ubiquitous force with so much empirical evidence that it has its own law of thermodynamics. There are too many cellular pathways that would have to be halted or reversed in order to alter aging. But if we were mice, this inevitable process would culminate in two years, not 85 years; if we were dogs in about 12 years. The extreme elasticity of aging is evident in the range of lifespans among our mammalian cousins.
Indeed, the plasticity of lifespan across species is not mere accident, but a consequence of one of the central levers of evolution. In his 1977 book Ontogeny and Phylogeny, Steven J. Gould provides a persuasive account of how changes in the timing of developmental events have manifold consequences on size, form and life history, such that small alterations in the regulatory genes governing these processes may be a central mechanism of evolution. Seen in this way, lifespan is a fundamental part of the identity of an organism. It is a well-accepted rule that natural selection among complexly social animals favors delayed development; this delay permits the expansion of the central nervous system necessary for complex social life and a prolonged apprenticeship before sexual maturation. Such trends among social animals have reached an extreme in humans: we exhibit delayed sexual maturation, long gestation, reduced number of offspring and long and intense parental support.
As social complexity has increased through cultural evolution, our need for increased differentiation and specialization has outstripped even our extreme biological adaptations. In my own field of medicine, it is typical for training and apprenticeship to extend well into the fourth decade of life. Recently, in vitro fertilization has been enthusiastically adopted into our culture to allow women to defer childbearing beyond their natural period of fertility, permitting women to more fully participate and compete in the workplace. Among most people I know, technology-assisted pregnancy in one's fifth decade is seen as more normal than pregnancy in one's late teens, a time where natural fertility is near its peak. Given their early, yet unmistakable, signs of talent and ambition, and the ever-increasing complexity of the global society and market in which they'll need to find their place, my own daughters (ages two and six) might well opt to defer childbearing until well after they are 40. Indeed, should they choose to do so, I am certain that they will have the technology to enable this choice, and perhaps also anti-aging agents that would still permit them to dance at their own grandchildren's weddings.
In this way, resveratrol-like agents may truly be medicines for the 21st century, permitting humans to tinker with the clock of our own development. Through such means we may be able to adjust our life history to meet the demands of an emerging society that changes in ways that seem beyond our control. Judging from our past behavior, it is hard to imagine that science or the marketplace will pause very long to consider the important questions raised by the possibility of life-prolonging pharmaceuticals. It seems hardly a fair fight when the potential and uncertain consequences to society are pitted against the urgent, deeply rooted, biologically programmed desires and demands of the individuals of which it is composed.
- Fries, J. F. 1983. The compression of morbidity. The Millbank Memorial Fund Quarterly 61:397-419.
- Fries, J. F. 1980. Aging, natural death and the compression of morbidity. The New England Journal of Medicine 303:130-135.
- Wood, J., et al. 2004. Sirtuin activators mimic calorie restriction and delay aging in metazoans. Nature 430:686-689.