group of cases, i.e. being all centenarians. Indeed, a well accepted approach for identifying those genetic factors that are associated with ‘longevity assurance’ is to study the genotype of centenarians. These people are the survival tail of population, and living 100 or more years is a rare phenotype, i.e. #1 every 10,000 people [1,2]. However, our results should be taken with caution due to the relatively low number of centenarians we studied. Indeed, a sample size of ,400 centenarians would have been needed in order to reach sufficient statistical power ($0.8). To note is that we only included males in the two athletic cohorts due to the higher competition success (at the international level) of Spanish male athletes compared to their women counterparts. This ensured that both cohorts were really in both end-points of the human performance continuum. With regards to this, it must be kept in mind that the X allele seems to be more influential to elite athletic status in women than in men [9]. It thus remains to be determined if our results can be corroborated with women’s athletic cohorts. Future studies are also necessary with larger samples of centenarian males in order to replicate the findings we obtained with our cohort of centenarians, which was mainly composed of women. On the other hand, longevity is likely a complex, polygenic trait, which could be influenced by numerous gene- environment and gene-gene interactions, including those interac- tions between genetic variants that might not influence longevity individually.

Author Contributions

Subject (centenarians) gathering: GR-R NG AC-N. Conceived and designed the experiments: AL CS JRR MM. Performed the experiments: CF-L GR-R CS FG-G TY. Analyzed the data: AL JRR. Contributed reagents/materials/analysis tools: AC-N NG. Wrote the paper: AL JRR MM.

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