ИСТИНА

An increase in the probability of death is a defining characteristic of aging. Paradoxically, however, prenatal and early childhood mortality decrease with age. This observation and the notion that the force of natural selection declines with age are often interpreted as that organismal aging begins after the onset of reproduction. However, we find that mortality and/or incidence of diseases associated with aging, such as cancer and heart and infectious diseases, follow a U-shaped curve, with the minimum noticeably below the onset of reproduction. In addition, quantitative biomarkers of aging, including somatic mutations and age-dependent patterns in DNA methylation, change monotonously throughout lifetime, arguing against the relationship between early life mortality and aging. Analyses of gene knockouts, selection coefficients and expression patterns support decreasing lethality during development, pointing to the contribution of parental mutations to early mortality. The data indicate that early life mortality can be explained, in part, by negative selection against parental damaging mutations that start manifesting when the corresponding genes are first expressed. This selection allows populations to persist despite significant mutation rates and to alleviate an increase in genetic burden. Deconvolution of age-related patterns of mortality and deleterious changes points to conception as the beginning of aging. The work was supported by the Russian Federation grant №14.W03.31.0012.