Aging and Longevity between Genetic Background and Lifestyle Intervention

The search for the genetic and molecular basis of aging and longevity has blossomed over the past few decades. Many (correctly, in our opinion) consider that this scientific field started with the experiments of Tom Johnson in the 80s of the last century. Indeed, before then, most gerontologists not only proclaimed the lack of progress in the field, but also suggested that progress in the field was not possible because aging is ineluctable. In their view, aging occurs after reproduction, and then there is no need and also no opportunity for selection to act on genes that are expressed late in life. The analysis of hybrids obtained from different strains of C. elegans allowed estimating the heritability of lifespan to be between 20% and 50%. In addition, Johnson found that mutations in a specific gene, named Age1, were able to significantly increase lifespan. These experiments triggered a number of genetic studies in both humans and model organisms aimed at identifying the genes and the biochemical pathways that can modulate lifespan. This fruitful quest led to the identification of genes strictly correlated with the maintenance of the cell and of its basic metabolism. Indeed, mutations in genes encoding proteins involved in DNA repair, telomere conservation, heat shock response, and the management of free radicals' levels were found to contribute to longevity or, in case of reduced functionality, to accelerated senescence (cellular aging) and the consequent organism aging. Concurrent efforts also showed that genes implicated in lipoprotein metabolism (especially APOE), immunity, and inflammation play a role in aging, age-related disorders, and organism longevity. Overall, these observations led to the idea that longevity may arise from a particularly efficient process of maintenance of the cellular and organismal activities that could contrast the inevitable time related decline of the organism functionality, which in turn leads to death. In parallel to the studies mentioned above, a substantial number of findings in model organisms suggested that longevity could " directly " be promoted by some specific pathways. These studies were mostly driven by the finding that calorie restriction (which is a reduction in nutrient intake in the absence of malnutrition) leads to a significant lifespan increase in a variety of organisms. The identification of pathways involved in the molecular mechanisms modulated by calorie restriction has shown that this dietary regime induces an arrest of the start of cell division; consequently, the cell enters in a quiescent …