Reviewing Epigenetic Inheritance of Longevity

Natural variations in longevity can be inherited to some degree, but one of the more interesting findings in recent years is that induced longevity as a result of environmental circumstances such as calorie restriction or gene therapies applied to adults only, and thus not inherited, can also produce extended longevity in offspring. Researchers were initially quite surprised to find that even limited forms of Lamarkian inheritance could exist. The proposed mechanism is inheritance of epigenetic markers, decorations to DNA that control the degree to which specific proteins are produced from their genetic blueprints. This open access paper reviews what is known on this topic.

Until recent years, a basic assumption in biology was that mutations in the DNA sequence were the only source of heritable phenotypic variation. It is commonly believed that genetic information may be transmitted to the next generations by germ cells only, while somatic cells do not have any inheritance function. The core of this theory is the idea that information is not capable of being transferred from somatic to germline cells and, respectively, to the next generations. This concept is commonly referred to as the Weismann's barrier. According to this concept, a strict distinction exists between innate and acquired characters. There is, however, significant empirical evidence to suggest that the Weismann's barrier is not entirely impermeable and can be crossed.

Examples for non-DNA sequence-based inheritance across generations have been obtained in a variety of species, including microbes, plants, worms, flies, fish, rodents, pigs, and humans. Many recent papers highlight the role of epigenetic mechanisms in mediating these effects. These processes include modified patterns of DNA methylation and histone posttranslational modifications, replacement of canonical histones with histone variants, as well as altered noncoding RNA expression causing changed local accessibility to the genetic material and modified gene expression. In several recent studies, the potential importance of non-genomic transgenerational effects in the inheritance of age-related characteristics has been highlighted. However, the transgenerational effects on longevity have been reported only rarely to date. Most of the papers reviewing and discussing such effects are focused solely on data obtained from the nematode Caenorabditis elegans, although similar findings were obtained in other species as well.

In evolutionary terms, the transmission of the adaptive transcriptional patterns acquired throughout the parental life course in subsequent generations via the mechanism of epigenetic memory can enable the organism to better survive in potentially adverse environments. In particular, it has been repeatedly reported that offspring of parents exposed to nutritional stresses exhibit altered expression of genes related to metabolic functions including those implicated in pro-longevity metabolic pathways. The mechanisms potentially responsible for such inter- and transgenerational effects are currently the subject of active investigation. In most studies on short-lived models such as nematodes and flies, the role of histone modifications in transgenerational transmission of epigenetic information was highlighted, while in rodent models changes in DNA methylation have been mainly detected.


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