Genetics and Genomics of Human Longevity

摘要: Longevity is a complex trait which gene–gene, gene–environment, and environment–environment interactions all play important roles in regulating. Candidate gene-based case-control studies, longitudinal studies with long-term follow-up, genome/epigenome-wide association linkage contribute to accumulate current understandings toward human longevity. Up now, near 300 (3-fold increase within 4 years) potential genes are involved Based on their functions, these approximately categorised into lipid–lipoprotein metabolism, insulin/IGF1 signalling pathway, genome integrity, inflammation. Epigenetic regulation gene expression without changing the primary deoxyribonucleic acid sequence becoming aging Increasing evidence from genome-wide methylation pattern (methylome) small noncoding ribonucleic acids implies higher level of regulating mechanism control longevity genes. Yet lacking replicated result besides APOE FOXO3A among overwhelming explosion data still remains as concern. Nevertheless, advancing knowledge gives prevent age-related diseases, hopefully extend lifespan. Key Concepts: Healthy or people often defined population very late age at death survival extreme high physical cognitive functioning absence major chronic diseases. Several fundamental cellular processes integrity inflammations closely associated longevity. Hypothesis-driven (candidate studies) hypothesis-free (genome-wide association/linkage approaches used study longevity. APOE most extensively studied longevity-related genes, however, only variants consistently throughout using different recruiting various ethnic populations. The rise epigenetic suggests controlling genetic impact. The presence beneficial alleles contributes phenotype rather than diseases-associated alleles. Keywords: aging; genetics; epigenetics; human; longevity; polymorphisms