Sunday, October 14, 2018

We discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life & enhance health under laboratory conditions; does this support George Williams’ 1957 paper aobut antagonistic pleiotropy hypothesis of aging?

Is Antagonistic Pleiotropy Ubiquitous in Aging Biology? Steven N Austad Jessica M Hoffman.  Evolution, Medicine, and Public Health, eoy033, https://doi.org/10.1093/emph/eoy033

Abstract: George Williams’ 1957 paper developed the antagonistic pleiotropy hypothesis of aging, which had previously been hinted at by Peter Medawar. Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge. No genes of the sort hypothesized by Williams were known sixty years ago, but modern molecular biology has now discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life and enhance health under laboratory conditions. Does this provide strong support for Williams’ hypothesis? What are the implications of Williams’ hypothesis for the modern goal of medically intervening to enhance and prolong human health? Here we briefly review the current state of knowledge on antagonistic pleiotropy both under wild and laboratory conditions. Overall, whenever antagonistic pleiotropy effects have been seriously investigated, they have been found. However, not all trade-offs are directly between reproduction and longevity as is often assumed. The discovery that antagonistic pleiotropy is common if not ubiquitous implies that a number of molecular mechanisms of aging may be widely shared among organisms and that these mechanisms of aging can be potentially alleviated by targeted interventions.

Topic: aging phenotype genes longevity molecular biology reproductive physiological process pleiotropism elderly

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