Fig. 1: Rapamycin slows age-related decrements in whole-body muscle function and metabolism.

a Body mass for mouse groups receiving rapamycin (~4 mg kg⁻¹ day⁻¹) or control diet beginning at 15 months (CON-middle and RM-middle) or 20 months (CON-late and RM-late) of age; n = 18 (CON-middle), 17 (RM-middle), 5 (CON-late), and 9 (RM-late) mice. b Mean daily food intake for middle-aged groups; n = 18 (CON-middle) and 17 (RM-middle) mice. Bimonthly recordings of whole-body lean (c) and fat mass (d); n = 18 (CON-middle), 17 (RM-middle), 6 (CON-late), and 9 (RM-late) mice. e All-limb grip strength normalized to body mass; n = 19 (CON-middle), 18 (RM-middle), 6 (CON-late), and 9 (RM-late) mice. f Twenty-four hours of voluntary running-wheel distance; n = 16 (CON-middle), 15 (RM-middle), 6 (CON-late), and 9 (RM-late) mice. Note that improvements by rapamycin were similar, irrespective of the time of treatment onset. g Kaplan–Meier plot for the inverted grip-hang test performed prior to endpoint measures at 30 months of age for the middle-aged group; n = 11 (10mCON), 18 (CON-middle), and 18 (RM-middle) mice. h Gait analysis of forelimb- and hindlimb-stride length at 28 months of age for middle-aged groups; n = 8 (8mCON), 9 (CON-middle), and 10 (RM-middle) mice. i Whole-body metabolic analysis of energy expenditure normalized to body surface area reported every 2 h across one full day (white)/night (black) cycle in the month prior to endpoint measures and j mean day and night values recorded at 25 and 30 months of age for middle-aged groups; n = 12 (10mCON), 14 (25mCON), 13 (25mRM), 9 (30mCON), and 10 (30mRM) mice. Data are presented as mean ± SEM. For a, b, e, and f, both control groups (CON-late and CON-middle) and both RM groups (RM-late and RM-middle) were combined for statistical comparisons. Two-way repeated-measure ANOVA with Sidak or Tukey post hoc tests (a–f, i–j), Mantel–Cox log rank (g), and one-way ANOVA with Fisher’s LSD post hoc tests (h) was used to compare the data. *, **, and *** denote a significant difference between groups of P < 0.05, P < 0.01, and P < 0.001, respectively. # denotes a trend where 0.05 < P < 0.10. Colored asterisks refer to the group of comparison.