The three genetics (nuclear DNA, mitochondrial DNA, and gut microbiome) of longevity in humans considered as metaorganisms

Abstract

Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between nDNA/mtDNA and the environment is most likely involved in phenomena such as ageing and longevity. To this scenario we have to add another level of complexity represented by the microbiota, that is, the whole set of bacteria present in the different part of our body with their whole set of genes. In particular, several studies investigated the role of gut microbiota (GM) modifications in ageing and longevity and an age-related GM signature was found. In this view, human being must be considered as "metaorganism" and a more holistic approach is necessary to grasp the complex dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host during ageing. In this review, the relationship between the three genetics and human longevity is addressed to point out that a comprehensive view will allow the researchers to properly address the complex interactions that occur during human lifespan.

Figure 1

Schematic representation of the remodeling theory. The genetics-environment interactions as a function of age are represented as the fitness between the screwdrivers (genotype) and screw head shape (cross or cut). In particular, the different gene-environment interaction is represented by different ratio between the screw head shape. According to the remodeling theory, the interaction between the same genotype and time-related physiological conditions could result in different fitness, as shown in the three plots (fitness versus age). In particular, the highest fitness values for each genotype are coloured (red, blue, and green).