Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species

Abstract

Accumulating animal and human data indicate that environmental exposures experienced during sensitive developmental periods may strongly influence risk of adult disease. Moreover, the effects triggered by developmental environmental cues can be transgenerationally transmitted, potentially affecting offspring health outcomes. Increasing evidence suggests a central role of epigenetic mechanisms (heritable alterations in gene expression occurring without changes in underlying DNA sequence) in mediating these effects. This review summarizes the findings from animal models, including worms, insects, and rodents, and also from human studies, indicating that lifespan and longevity-associated characteristics can be transmitted across generations via non-genetic factors.

Keywords: Age-associated disease; Aging; DNA methylation; Epigenetics; Longevity; Transgenerational inheritance.

Fig. 1

Distinction between intergenerational and transgenerational inheritance in mammals. In the case of intergenerational inheritance, parental exposures directly influence not only embryos and/or fetuses (F1 generation), but also already developing germ cells, giving rise to the F2 generation. Thus, F1 and F2 phenotypes may be directly exposed to external developmental cues, and F3 generation is the first one where the phenotype is not through primary triggering exposure. Therefore, true transgenerational effects include those that persist into the F3 generation [8]

Fig. 2

Genome-wide demethylation and de novo DNA methylation processes in the mammalian germline and in preimplantation embryos. The levels of global DNA methylation are indicated on the y-axis and are shown by a blue line for the paternal genome and a pink line for the maternal genome. The top bar schematically presents waves of demethylation followed by de novo methylation in F0–F3 generations

Fig. 3

Potential mechanisms of transgenerational transmission of environmentally induced effects through both maternal and paternal lines (black letters) or only the maternal line (red letters). The figure is based on hypothetical mechanisms suggested by Heard and Martienssen [90] to explain transgenerational inheritance of acquired information