Empirical verification of evolutionary theories of aging

Abstract

We recently selected 3 long-lived mutant strains of Saccharomyces cerevisiae by a lasting exposure to exogenous lithocholic acid. Each mutant strain can maintain the extended chronological lifespan after numerous passages in medium without lithocholic acid. In this study, we used these long-lived yeast mutants for empirical verification of evolutionary theories of aging. We provide evidence that the dominant polygenic trait extending longevity of each of these mutants 1) does not affect such key features of early-life fitness as the exponential growth rate, efficacy of post-exponential growth and fecundity; and 2) enhances such features of early-life fitness as susceptibility to chronic exogenous stresses, and the resistance to apoptotic and liponecrotic forms of programmed cell death. These findings validate evolutionary theories of programmed aging. We also demonstrate that under laboratory conditions that imitate the process of natural selection within an ecosystem, each of these long-lived mutant strains is forced out of the ecosystem by the parental wild-type strain exhibiting shorter lifespan. We therefore concluded that yeast cells have evolved some mechanisms for limiting their lifespan upon reaching a certain chronological age. These mechanisms drive the evolution of yeast longevity towards maintaining a finite yeast chronological lifespan within ecosystems.

Time for the systems-level integration of aging: Resilience enhancing strategies to prevent Alzheimer’s disease

“…The discovery of an intrinsic (genetic) regulation of aging-related processes has raised the not yet unresolved intellectual conflict between evolutionary theorist which debate on whether aging may represent either an evolutionary adaptive response (adaptive aging ultimately called aging by design) or not (Goldsmith, 2008;Kyryakov et al, 2016). An adaptive aging counteracts the traditional evolutionary approach which rules out the possibility of an intrinsically determined selfdefeating biological program (in terms of survival and reproduction) that does not bring about any short-or long-term benefit (non-programmed aging theory).…”

Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae

“…of prolonging yeast CLS has identified lithocholic bile acid (LCA) as one of such geroprotectors (162). Yeast cells do not produce LCA or other bile acids, all of which are synthesized and released into an ecosystem by animals and humans (174)(175)(176)(177). If LCA is added exogenously to yeast cultured in a liquid medium, this highly hydrophobic bile acid enters the yeast cell, is delivered to mitochondria, accumulates mainly in the inner mitochondrial membrane (IMM) and also associates with the outer mitochondrial membrane (OMM) (178).…”

Mechanisms Underlying the Essential Role of Mitochondrial Membrane Lipids in Yeast Chronological Aging

“…Unlike animals and humans, yeast cells do not synthesize bile acids [ 130 – 133 ]. Thus, a mechanism through which exogenously added LCA delays yeast chronological aging may or may not involve its entry into the yeast cell and, perhaps, a delivery of this highly hydrophobic bile acid to some specific location(s) within the cell.…”