Figure 6.

Senolytics extend both health- and life-span in aged mice. (a) Experimental design for physical function measurements in 20-month-old male mice treated with D+Q once every 2 weeks (bi-weekly) for 4 months. (b-h) Maximal walking speed (relative to baseline) (b), hanging endurance (c), grip strength (d), body weight change from baseline (e), treadmill endurance (f), daily activity (g), and food intake (h) of 20-month-old male C57BL/6 mice 4 mo after drug initiation (n = 20 for D+Q; n = 13 for V). (i) The relative mRNA abundance for target genes of visceral adipose tissue from 6-month-old non-treated (6m, n = 7), 24-month-old V-treated (24m-V, n = 8), and 24-month-old D+Q-treated (24m-DQ, n = 8) mice. (j) Experimental design for lifespan analyses. (k,l) Post-treatment survival curves (k) and whole-life survival curves (l) of C57BL/6 mice treated bi-weekly with D+Q (n = 71; 40 males, 31 females) or V (n = 76; 41 males, 35 females) starting at 24-27 months of age. Median survival is indicated for all curves. (m) Maximal walking speed and hanging endurance averaged over the last 2 months of life and lifespan for the longest living mice (top 40%) in both groups for both sexes. For male mice, n = 12 for D+Q and n = 12 for V. For female mice, n = 13 for D+Q and n = 13 for V. (n) Disease burden and tumor burden at death. For both sexes, n = 59 for D+Q, n = 62 for V. For males, n = 30 for D+Q, n = 29 for V. For females, n = 29 for D+Q, n = 33 for V. (b-i, m) Results are shown as box and whiskers plots, where a box extends from the 25th to 75th percentile with the median shown as a line in the middle, and whiskers indicate smallest and largest values. (n) Results are shown as mean ± s.e.m. *P <0.05; n.s., not significant; Two-tailed Student’s t-tests (b-i, m-n) and Cox proportional hazard regression model (k-l).