Klotho polymorphisms and longevity: a systematic review - Calogero Caruso

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Nowadays is clearly evident that genetic background constitutes integral part of successful ageing and longevity. Many studies on long lived people have been conducted emphasizing the role of certain genes in long life. Classic case-control studies, genome wide association studies and high throughput sequencing have permitted to identify a variety of genetic variants seemingly associated to longevity. Over the years, ageing research has focused on insulin/IGF-1 signaling pathway because of its evolutionary conserved correlation with life-span extension in model animals. Indeed, many single nucleotide polymorphisms (SNPs), associated with longevity were identified in genes encoding proteins that take part in this metabolic pathway. Recently we have conducted a meta-analysis that has showed the association of IGF-1R and FOXO3A polymorphisms with longevity. Closely related to this pathway is the Klotho gene. It encodes a type-I membrane protein expressed primarily in the kidney in two forms, membrane and secreted. The last form acts suppressing oxidative stress and growth factor signalling and regulating ion channels and trasporters. Its overexpression seems to be able to suppress insulin/IGF-1 signaling extending life span as showed in transgenic mice.

Thus, our aim is to put together the results showed in literature concerning the association between SNPs of Klotho and longevity to quantify the possible effect of each single SNP and its magnitude. The results of our systematic review indicate that Klotho SNPs are associated with ageing.