Association of the K153R polymorphism in the myostatin gene and extreme longevity

Abstract

The myostatin (MSTN) gene is a candidate to influence extreme longevity owing to its role in modulating muscle mass and sarcopenia and especially in inhibiting the main nutrient-sensing pathway involved in longevity, i.e. mammalian target of rapamycin. We compared allele/genotype distributions of the exonic MSTN variants K153R (rs1805086), E164K (rs35781413), I225T and P198A, in Spanish centenarians (cases, n=156; 132 women, age range 100-111 years) and younger adults (controls, n=384; 167 women, age <50 years). No subject of eithergroup carried a mutant allele of the E164K, I225T or P198A variation. The frequency of the variant R allele was significantly higher in centenarians (7.1 %) than in controls (2.7 %) (P=0.001). The odds ratio of being a centenarian if the subject had the R allele was 3.48 (95 % confidence interval 1.67-7.28, P=0.001), compared to the control group, after adjusting for sex. The results were replicated in an Italian cohort (centenarians, n=79 (40 women), age range 100-104 years; younger controls, n=316 (155 women), age <50 years), where ahigher frequency of the R allele in centenarians (7.6 %) compared to controls (3.0 %) (P=0.004) was independentlyconfirmed. Although more research is needed, the variant allele of the MSTN K153R polymorphism could be among the genetic contributors associated with exceptional longevity. © American Aging Association 2013.