A Experimental scheme for animal studies. Three independent groups of mice at ages 2, 9–11, or 18–20 months old were examined in open field, grip strength, and hanging tests. Following tests, mice were euthanatized, then spinal cord and lumbrical muscle were collected for analyses shown in Figs. 2 and S3. Key behavioral tests are shown in B grip strength and C hanging tests. (2 months old, WT: n = 18, CKO: n = 15; 9–11 months old, WT: n = 15, CKO: n = 14; 18–20 months old, n = 16/groups). EchoMRI body composition analyses are shown in D body weight, and E lean muscle mass. F Illustration of in vivo muscle contractility measurement. Contractility of the anterior crural muscle was assessed by stimulating the peroneal nerve and recorded as isometric tetanic torque at the ankle of 20 months old mice. Muscle contractility tests determine G peak isometric torque, H TA muscle weight, and I normalized peak isometric torque. J Representative H&E images of a TA muscle from 20 months old mice (Scale bar is 20 μm). K Quantification of the cross-sectional area (CSA) of TA muscle fibers. Results are presented as means ± SD, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, compared with WT group. #p ≤ 0.05, ##p ≤ 0.01, compared with same genotype group at 2 months old.