Fig. 1: SIRT6 regulates lifespan and healthspan of C57BL/6JOlaHsd mice of both sexes.

a Kaplan–Meier survival curves for male, female, and combined sexes of WT (n = 52 males, n = 50 females), SIRT1-tg (n = 47 males, n = 30 females), SIRT6-tg (n = 51 males, n = 41 females), and SIRT1 + 6-tg (n = 47 males, n = 44 females) mice. p-values for SIRT6-tg vs. WT mice are shown and were derived from two-tailed log-rank calculations. Median lifespan for each genotype is shown in parentheses. b–d Neoplasia (b), cancer (c), and gastrointestinal adenoma (d) incidence at the age of 25 months. For (b–d), n = 16 mice per genotype, a mixture of both sexes. Two-tailed Fisher’s exact test; *p < 0.05 vs. WT. Exact p-values are reported in Supplementary Table 1. e Respiratory exchange ratio (RER) averaged over 3 days in young and old WT and SIRT6-tg mice from either sex measured every half-hour. Three-way ANOVA with repeated measures with age, genotype, and time as variables. Sidak’s post hoc; young WT (* in blue) or old SIRT6 (* in green) vs. old WT. n = 8 mice per group, except for young SIRT6 where n = 7 mice. f Spontaneous wheel running activity of males at the ages of 8 months (n = 8 mice per genotype) and 15 months (n = 9 mice for WT, SIRT1, SIRT6, n = 7 mice for SIRT1 + 6). Two-way ANOVA with time and genotype as variables. g Exercise ability on treadmill in young and old males. Two-way ANOVA with Sidak’s post hoc. n = 6 mice per group, except for young WT where n = 5 mice. *p < 0.05, **p < 0.01, ***p < 0.001. In (e) and (f), values are shown as mean ± SEM. In (g), box extends from the 25th to 75th percentiles, line in the middle of the box is the median and whiskers go down to the smallest value and up to the largest. For (e–g), exact p-values are reported in the Source Data file.