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We observe a synergy effect in individuals holding both the CC or CT rs4880 MnSOD genotypes and the TT or CT rs1050450 GPX1 genotypes, indicating that this genetic combination may influence human longevity in a positive direction. A synergy effect of the rs4880 MnSOD and rs1050450 GPX1 SNP genotypes has been reported once before; Cox et al. (2006) observed no association with breast cancer of the two SNPs independently, yet individuals holding both the rs4880 MnSOD CC and rs1050450 GPX1 TT genotypes showed increased breast cancer risk as compared to individuals holding both the rs4880 MnSOD TT and rs1050450 GPX1 CC genotypes. Finally, the sensitivity towards oxidative stress in Sod2+/(cid:3)/GPx1(cid:3)/(cid:3) mice has been found to be more than additive as compared to Sod2+/(cid:3) or GPx1(cid:3)/(cid:3) mice (Van Remmen et al., 2004), thus supporting a synergetic effect of MnSOD and GPX1 activities.

Finally, we investigated whether the two SNPs were associated with the functional and cognitive abilities of the elderly. Our results indicate that the SNPs may affect these age-related phenotypes in a modest manner.

Our data implies a moderate effect of the CC/CT rs4880 MnSOD SNP and TT/CT rs1050450 GPX1 SNP genotypes on good self rated health (yet, non-significant for rs1050450) and a moderate effect on increased ADL strength scores (yet, non-significant for rs4880). Looking at the CT and TT rs1050450 GPX SNP genotypes separately showed the same tendencies. These finding might indicate that the individuals holding the genotypes associated with decreased mortality might have had slightly better functional abilities.

The MMSE scores were used for evaluation of the cognitive functioning of the elderly. The values used were intake scores, since it has been shown previously that the MMSE scores at intake is heritable, while rate of change is not (McGue and Christensen, 2002). Wefound a moderateeffect of the rs4880MnSOD SNP CC/CT genotype on increase in MMSE, indicating that the individuals holding the genotypes associated with decreased mortality also had slightly better cognitive abilities. As mentioned earlier, the rs4880 MnSOD SNP CC/CT genotype might be the genotype with the highest activity. Notably, centenarians having the highest Cu/ ZnSOD activity have been found also to hold the highest cognitive capacity (Andersen et al., 1998). Our results indicate that this might also be the case for MnSOD.

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