Persistence of developmentally programmed effects across generations: Impact on longevity

摘要

A number of recent studies have provided evidence that environmental exposures during early life may have profound consequences for the individual’s life-course health and aging trajectory. Several studies have also revealed that detrimental outcomes of early-life stresses may be transgenerationally transmitted via non-genomic pathways and thereby can influence the adult health status in subsequent generations. The programming effects of early-life adverse conditions may be mediated by epigenetic mechanisms, including DNA cytosine methylation, histone modifications and several RNA-associated regulatory systems. It is generally assumed that the global resetting of epigenetic marks takes place during gametogenesis and embryogenesis. In several cases, however, the epigenetic marks are not completely erased in germ cells, and transgenerational inheritance of epigenetic information can occur. Recent evidence has shown that several epigenetic marks are likely retained and reproduced in the offspring. The aim of this mini-review is to provide a summary of theoretical models and recent experimental and epidemiological findings that indicate that early-life conditions may program the late-life health status and longevity across generations.