Researchers are turning up a great many human genetic variants associated with natural differences in longevity - a complex, patchwork array of them, each contributing a small amount to the whole: "Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-?) genes may influence human life-expectancy. ... SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes ... Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males ... a significant two-loci interaction occurs in females between ADA 22G>A and TNF-? -238G>A ... both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-? genes can influence life-expectancy in a gender-specific manner and that males and females follow different pathways to attain longevity."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21865054

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