Nature, Nurture, and Chance: Their Roles in Interspecific and Intraspecific Modulations of Aging

Abstract

The constitutional genome, its environment, and a range of stochastic events all interact to produce virtually unique patterns of lifespan and health span. This is certainly the case for genetically heterogeneous organisms living in the wild, but there is growing evidence of considerable variations even among inbred organisms maintained in the laboratory. When one compares different species, it is clear that the dominant variable is the constitutional genome. I shall argue, however, that stochastic events are the dominant variables among members of the same species. Somatic mutations clearly play important roles. Leslie Orgel' s protein synthesis error catastrophe remains a potential mechanism because it has been insuffi ciently tested in vivo. The recent discovery of widespread random clonal monoallelic expression in the laboratory of Andrew Chess provides yet another layer of complexity. Perhaps the most cogent explanation of the growing phenotypic variations among aging cohorts, however, are increasing drifts in gene expression with age, presumably epigenetic in origin, but conceivably also driven by posttranscriptional mechanisms. I shall argue that such drifts evolved because they proved adaptive to groups of organisms in unpredictable environments, but that age-related expansions of such variegated gene expressions will have escaped the force of natural selection and are responsible for a wide range of quasi-stochastic geriatric pathologies, both proliferative and degenerative. ANNUAL REVIEW OF GERONTOLOGY AND GERIATRICS

Facilitation of environmental adaptation and evolution by epigenetic phenotype variation: insights from clonal, invasive, polyploid, and domesticated animals

“…For example, differences in adult body weight among identically raised littermates of inbred rat were shown to have their roots in stochastic events in the zygote and first cleavage stages [ 36 ], whereas in isogenic batch-mates of marbled crayfish such differences were more attributable to the adult life [ 24 ]. SPV-related differences in ageing and diseases of humans can have their origin in both early development and the later life [ 37 , 38 ]. Similar sensitive windows also exist for EPV [ 3 , 33 , 39 ].…”