Experimental Gerontology (Jun 2023)
How does the body know how old it is?
Abstract
Based on the ideas of R. A. Fisher, neoDarwinism came to dominate evolutionary science in the first half of the wentieth entury, and within that perspective aging could never be an evolved adaptation. But as the genetic and epigenetic mechanisms of aging came to be elucidated in many species, the signature of an adaptation became clear. Simultaneously, evolutionary theorists were proposing diverse selective mechanisms that might account for adaptations that are beneficial to the community, even as they imposed a fitness cost on the individual. Epigenetic conceptions of aging gained currency with the development of methylation clocks beginning in 2013. The idea that aging is an epigenetic program has propitious implications for the feasibility of medical rejuvenation. It should be easier to intervene in the body's age-related signaling, or even to reprogram the body's epigenetics, compared to brute-force repair of all the physical and chemical damage that accrues with age. The upstream clock mechanism(s) that control the timing of growth, development, and aging remain obscure. I propose that because of the need of all biological systems to be homeostatic, we should expect that aging is controlled by multiple, independent timekeepers. A single point of intervention may be available in the signaling that these clocks use to coordinate information about the age of the body. This may be a way of understanding the successes to date of plasma-based rejuvenation.
