Alu Polymorphisms of Autophagy and Apoptosis Regulatory Genes as Human Lifespan Factors

Abstract— To assess the contribution to survival of Alu insertions in the ACE, PLAT, COL13A1, LAMA2, CDH4, SEMA6A, PKHD1L1, STK38L, HECW1, and TEAD1 genes, which are candidates of aging and longevity, amid the senile physiological and pathological phenotype, an analysis of association with life expectancy was carried out. Survival and mortality data were obtained for 1382 elderly people who were selected from the sample of Tatars residing in the Republic of Bashkortostan (total 1790 people from 18 to 109 years). Mortality risk was higher among carriers of the STK38L Alu-insertion genotype (Ya5ac2145*II, HR = 2.07, P = 0.022). Alu insertion in the HECW1 and TEAD1 genes has demonstrated a survival protection effect (Ya5NBC182*II, HR = 0.71, P = 0.038 and Ya5ac2013*II, HR = 0.74, P = 0.035 respectively). The survival amid the persons with various clinical phenotypes was associated with the Alu polymorphism of the SEMA6A (Yb8NBC597*ID, HR = 0.54, P = 0.016 for the cerebrovascular diseases), TEAD1 (Ya5ac2013*II, HR = 0.57, P = 0.016 for the cardiovascular pathologies), and LAMA2 (Ya5-MLS19*ID, HR = 0.36, P = 0.03 for multimorbidity status) genes. Thus, the genes involved in the regulation of autophagy(definition) and apoptosis were associated with survival and longevity.