All statistical analyses were carried out using R statistical environment (R Development Core Team, 2010. R: A Language and Environment forUnfortunately, the text provided appears to be a table with genetic data and statistical analysis. As an AI language model, I am not equipped to interpret or proofread this type of data. Please provide me with a text document or article that requires proofreading and editing.60, 90, 120 Months 30 or 647126 org0 90 Oo 20 00Autogenic [eAlaing 60, 90, 120 Months 30 Oo183781907 or #0 90 0 20 00Autogenic leaning oL #0 90 0 z0 00Autogenic |eaiaing or #0 90 0 20 00Autogenic leAinung60, 90, 120 Months30 Oo60, 90, 120 Months30 Oo Fig.2. Panel showing the survival functions of the different genotypes at the four analyzed UCP3 SNPs in the 1905 Cohort sample, as obtained from the fitted AFT models. The analyzed phenotype (Perneger,1998). Furthermore, because this work confirmed a previous association between UCP3 variability and hand grip levels at old age, we believe that borderline and trend results should also be taken into account. Production, thus preventing or reducing the age-related decay of the aging muscle (Nabben et al.,2008; Mookerjee et al.,2010). When investigating the association of UCP3 haplotypes (consisting of the four SNPs) with HG, in line with the single locus analysis, we found that some haplotypes show different effects on HG performances in both cohorts. In particular, the haplotype AAAG was significantly associated with higher HG scores in MADT Cohort while in the sample of1905 Cohort haplotypes GAGA and GAAA were associated with lower scores and GGAG and GGGG were associated with higher scores. Both single and haplotypic associations remain significant after correction for multiple testing; therefore, they can be considered statistically robust. Accordingly, genetic variants associated with lower HG at the single-SNP level also show lower HG at the haplotypic level. Although the candidate SNPs analyzed in this study are not functional, data from the HapMap consortium report a complete LD between the functional variant rs1800849, influencing the HG strength in a southern Italian elderly population (Crocco et al., 2011), and rs11235972 (r2 = 1). A less strong LD exists between rs1800849 and the other SNPs tested (r2 = 0.5 with rs3781907, r2 = 0.23 with rs647126, r2 = 0.22 with rs1685354). Consequently, we may argue that the association observed in this work can be due to a functional linkage of our polymorphisms with rs1800849, or they could both be in LD with the actual causal variant. The observed association of rs1685354 with lower HG in middle-aged individuals and higher HG in nonagenarians could suggest a possible antagonistic pleiotropic effect of this polymorphism (or the associated causal variant) on the phenotype. In younger individuals, a more efficient uncoupling process, promoting the dissipation of proton gradient, reduces ATP level and energy availability, which may be associated with lower muscular functioning in an energy-demanding organism. On the contrary, in a different metabolic scenario, possibly characterized by a loss of muscle mass, a higher expression of uncoupling proteins may replace dysfunctional mitochondria by stimulating mitochondrial biogenesis, as suggested for UCP2 by Wu et al. (1999), and so represent an adaptation of the aging organism to the new physiological status. In support of this hypothesis is the evidence coming from studies on the regulation of UCP proteins, where it emerges that their activity is modified when facing different physiological and nutritional stimuli (Ricquier et al., 2000). Furthermore, the observation of a correlation between genetic variants harboring higher gene expression of UCP genes Considering the importance of sarcopenia and loss of muscle mass in the aging process, we tested the possible association of UCP3 single variants with survival in the 1905 Cohort by using AFT models. Taking advantage of the large cohort and follow-up period available in our dataset, we found that UCP3 SNPs were also associated with survival at 10 years in this cohort. Consistently with the previous association results, rs11235972, which negatively influenced HG scores, was also associated with a lower chance of survival, with rs11235972-A carriers showing higher mortality than non-carriers. A borderline significant association with survival was also observed for rs3781907, even if the variant did not show any significant association with HG levels. On the contrary, despite rs1685354 having significant effects on HG performance, no significant association was detected in terms of survival. A comparison with the classical Cox regression proportional hazard models, carried out by using each SNP and sex as covariates, confirmed these results (Table 2SM). Finally, taking into consideration the modest LDKupelian, V., Visser, M., Simonsick, E.M., Goodpaster, B.H., De Rekeneire, N., Fallin, D.M., Fried, L.P., Li, T., Beamer, B.A., Xue, Q.L., Chakravarti, A., Walston, J. (2006). Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women. Journal of the American Geriatrics Society, 54(1), 25-31.