Genomics of longevity: recent insights from research on centenarians

An ever larger portion of the world population survives into advanced old age, and that has been a steady trend for the last century. Despite some substantial advances in our understanding of the genomic basis of ageing in recent years, healthy ageing remains an increasingly important social task. Initially established in model organisms, many human orthologue genes and pathways associated with longevity have been identified. Ageing is a result from the declining ability of the human organism to maintain homeostatic balance and to regenerate damaged cells and tissues, and is the main risk factor for the prevalent diseases in developed countries. It could be imagined that the genome of very old individuals is purged of disease-causing variants, but recent studies have demonstrated that long-lived individuals carry the same number of disease alleles as young controls. Longevity may however also be explained by the presence of protective genetic factors against age-related phenotypes and diseases, and there is a pertinent need for these to be identified. Centenarians are the extreme phenotype of human longevity and their genomes undoubtedly contain clues about genes and pathways that are involved in longevity. Understanding the genomic basis of ageing, together with knowledge of population ecology and insights from evolutionary biology, will shed light on the biological mechanisms underlying human longevity and hence on the potential of extending healthy human life span.