Another interesting finding of our study was the association between the NOS3 rs10277237 and ADL scores. Subjects homozygous for the rs10277237-A allele had significantly better ADL performance compared with subjects with the other two genotypes. The inability of older adults to perform basic self-care independently is a consequence of a decline in physiological functions of multiple tissues. A contributor to this general decay is likely to be the reduction in endothelial cell function caused by the age-related impairment in the release of NO by NOS3. This reduces blood flow to all tissues in the body and thus the availability of nutrients for energy needs. Age-related changes in energy production and fuel utilization via mitochondrial dysfunction may also contribute to the decline in physical performance and disability among older adults. In this context, it is worth noting that recent studies have reported the existence of a mitochondrial NOS (mtNOS) isoform that seems to be both constitutive, mainly a post-translational isoform of NOS1, and inducible (Elfering et al. 2000; Lopez et al. 2006; Finocchietto et al. 2009). Because of its action on complex I and IV, NO in mitochondria may have important effects on oxidative phosphorylation and ROS/RNS production (Finocchietto et al. 2009). These effects may be amplified in a pro-oxidant environment such as in the case of aged individuals, with consequences particularly in tissues such as the brain and skeletal muscle, which are highly dependent on mitochondrial function.

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