For the human longevity phenotype, it is well known that most common genetic variants are likely to have only small to moderate effects (Christensen et al. 2006; Deelen et al. 2011; Nebel et al. 2011; Newman Barrett JC, Fry B, Maller J, Daly MJ ( ) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics: Bell JT, Tsai PC, Yang TP, Pidsley R, Nisbet J, Glass D, Mangino M, Zhai G, Zhang F, Valdes A, Shin SY, Dempster EL, Murray RM, Grundberg E, Hedman AK, Nica A, Small KS, Dermitzakis ET, McCarthy MI, Mill J, Spector TD, Deloukas P ( ) Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet: e doi:/journal.pgen. Benzi G, Moretti A ( ) Are reactive oxygen species involved in Alzheimer's disease? Neurobiol Aging: Bokov A, Chaudhuri A, Richardson A ( ) The role of oxidative damage and stress in aging. Mech Ageing Dev: Brioukhanov AL, Netrusov AI, Eggen RI ( ) The catalase and superoxide dismutase genes are transcriptionally up-regulated upon oxidative stress in the strictly anaerobic archaeon Methanosarcina barkeri. Microbiology: Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME ( ) Stress-dependent regulation of FOXO transcription factors by the SIRT deacetylase. Science: Budovsky A, Craig T, Wang J, Tacutu R, Csordas A, Lourenco J, Fraifeld VE, de Magalhaes JP ( ) Longevitap: a database of human genetic variants associated with longevity. Trends Genet. doi:/j.tig.

Compared to the effects of genetic components on human longevity determinants of lifespan differences have not yet been identified (Deelen et al. 2013). Environmental factors appear to be one of the major determinants of human longevity. The number of novel genetic findings contributing to human longevity is limited, highlighting the need for a large sample size to detect longevity variants. Meta-analyses can also be performed to identify candidate genes with modest influence. Alternative approaches, such as investigating structural variation, gene-gene interactions, or epigenetic mechanisms (e.g., miRNA, methylation patterns), are likely to improve our understanding of the interplay of the various genetic and environmental factors that influence human longevity (Bell et al. 2012; Christensen et al. 2006; Collino et al. 2013; ElSharawy et al. 2012; Gentilini et al. 2012; Glessner et al. 2013; Heyn et al. 2012; Kuningas et al. 2011; Sebastiani et al. 2011; Tan et al. 2002).