Searching for the longevity gene. Where are we heading?

Abstract Introduction: Human longevity is a complex phenotype with strong genetic components. Identifying the genetic factors which influence human longevity is a formidable challenge. The centenarian model provides us with a unique opportunity to face this challenge. The objective of the study was to diagnose the universality of applying studies on polymorphisms favouring longevity in people over 65 years of age. Materials and methods: Crucial articles were obtained by reviewing and analysing the PUBMED (MEDLINE) database by searching for the following entries: LEP/rs7799039, LEPR/rs1137100, FOXO1a/rs4943794, CETP/rs5882, TP53/rs1042522, IL6/ rs1800795, ACSL1 rs6552828, THRH/rs7832552, IL6/rs1800795, IGF- 1R/rs2229765, IGF-IR, IRS-1, FOXO1A, PI3KCB, testosteron (IGF-1) (DHEA-S), FOXO3 (MIM 602681), APOE, HRAS1, LASS1, CETP I405 V gene, CETP/rs9923854, APOE/rs769449, IL6/rs2069827, APOC3/rs2542052, MTP/rs2866164. Article selection was based on inclusion criteria set by the authors and the appointed Advisory Board. Results: Most of the identified gene variants are specific to a given population. Only a small group of genes consistently show up in various types of studies and in different populations. In humans, the influence of single genes on life expectancy is negligible. What gains significance is a set of genetic variants which favours longevity. There are numerous sets of such genes. Conclusions: The development of a new generation of sequencing techniques makes it possible to comprehend the genetic and epigenetic background of aging. Many researchers believe that aging is inevitable, but to some extent modifiable. Understanding the mechanisms responsible for aging may, in turn, indicate essential avenues of health promotion and disease prevention in middle age, so that elderly people could enjoy good health. Searching for polymorphisms specifically related to longevity enables the identification of new biological pathways connected to the control of life expectancy. Further research in this field could also help in developing more effective ways of treating age-related diseases.