Non negligible effects on physical functioning were also suggested for NDUFS1, which variability was found related to HG and WS in the whole sample. The strong association (p = 0.009) of the same gene with survival in the female subsample suggests that NDUFS1 gene, cod- ifying for the largest subunit of mitochondrial complex 1, and which mutations were correlated with inefficiency of oxidative phosphoryla- tion in Leigh Syndrome (Martín et al., 2005), can have a role also in the preservation of physical functioning at old age and lastly influence survival.

Supplementary data to this article can be found online at http:// dx.doi.org/10.1016/j.exger.2014.01.014.

Conflict of interest

Furthermore, very interesting is the association with MMSE levels (p = 0.005) observed in the whole sample for MT1A variability, overall found to be protective for cognitive functioning at SNP level. Consider- ing that the over expression of MT (metallothionein gene, member of a large family of proteins with anti-apoptotic effect) was the only dem- onstrated to increase mouse lifespan (Swindell, 2011), protecting against obesity and diet-induced oxidative damage, we may argue that these genes would deserve future attention for their relation with longevity and related phenotypes. Borderline effects on cognitive per- formances have been observed for NOS3 variability both in the male (p = 0.052 with MMSE) and female sample (p = 0.023 with CCS), in line with previous evidences indicating an association the gene with mild cognitive impairment (Solé-Padullés et al., 2004). Considering the recent evidence of association between the genetic variability of NOS1 and NOS3 genes with depressive symptoms and disability in a population from Southern Italy, finally influencing quality of aging and longevity (Montesanto et al., 2013), the present results suggest

Theauthorsdeclarenoconflictofinterestswhichcouldinfluencethe work.

Acknowledgments

This study was supported by the European Union's Seventh Frame- work Programme (FP7/2007–2011) under grant agreement no. 259679, the VELUX Foundation and the National Institute on Aging (P01 AG08761).

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