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How does the body know how old it is?

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EXPERIMENTAL GERONTOLOGY
卷 177, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2023.112182

关键词

Programmed aging; Methylation; Hypothalamus; Suprachiasmatic nucleus; Evolution of aging; Plasmapheresis

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Based on R. A. Fisher's ideas, neoDarwinism dominated evolutionary science in the first half of the twentieth century, and from that perspective, aging could never be seen as an evolved adaptation. However, as the genetic and epigenetic mechanisms of aging were elucidated, it became clear that aging has the signature of an adaptation. The development of methylation clocks since 2013 has further supported the idea that aging is an epigenetic program, which holds promise for medical rejuvenation.
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.

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