Molecular footprint of Medawar's mutation accumulation process in mammalian aging.

ABSTRACT: Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging-related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults. Combining 66 transcriptome datasets (including 16 tissues from five mammalian species) with sequence conservation estimates across mammals, here we report that the overall conservation level of expressed genes is lower at old age compared to young adulthood. This age-related decrease i

SUBMITTER: Turan ZG 

PROVIDER: S-EPMC6612638 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature