Genetic, Environmental, and Stochastic Components of Lifespan Variability: The Drosophila Paradigm.

Lifespan is a complex quantitative trait involving genetic and non-genetic factors as well as the peculiarities of ontogenesis. As with all quantitative traits, lifespan shows considerable variation within populations and between individuals. Drosophila, a favourite object of geneticists, has greatly advanced our understanding of how different forms of variability affect lifespan. This review considers the role of heritable genetic variability, phenotypic plasticity and stochastic variability in controlling lifespan in Drosophila melanogaster. We discuss the major historical milestones in the development of the genetic approach to study lifespan, the breeding of long-lived lines, advances in lifespan QTL mapping, the environmental factors that have the greatest influence on lifespan in laboratory maintained flies, and the mechanisms, by which individual development affects longevity. The interplay between approaches to study ageing and lifespan limitation will also be discussed. Particular attention will be paid to the interaction of different types of variability in the control of lifespan.

Drosophila as a Model Organism to Study Basic Mechanisms of Longevity.

The spatio-temporal regulation of gene expression determines the fate and function of various cells and tissues and, as a consequence, the correct development and functioning of complex organisms. Certain mechanisms of gene activity regulation provide adequate cell responses to changes in environmental factors. Aside from gene expression disorders that lead to various pathologies, alterations of expression of particular genes were shown to significantly decrease or increase the lifespan in a wide range of organisms from yeast to human. Drosophila fruit fly is an ideal model system to explore mechanisms of longevity and aging due to low cost, easy handling and maintenance, large number of progeny per adult, short life cycle and lifespan, relatively low number of paralogous genes, high evolutionary conservation of epigenetic mechanisms and signalling pathways, and availability of a wide range of tools to modulate gene expression in vivo. Here, we focus on the organization of the evolutionarily conserved signaling pathways whose components significantly influence the aging process and on the interconnections of these pathways with gene expression regulation.