Endurance training attenuates loss of bone strength in the polymerase gamma mutator mouse model of aging

A causal role for mtDNA mutagenesis in aging‐associated bone loss is supported by recent studies demonstrating that the polymerase gamma (PolG) mutator mouse, harbouring a proofreading‐deficient copy of PolG, exhibits a significant reduction in whole‐body bone mineral content and density. Physiological aging is accompanied by kyphosis, osteoporosis and an increased incidence of fractures. Anecdotal evidence from human and rodent studies suggests that endurance training prevents loss of bone mineral density, mobility and posture, and is recommended to reduce the likelihood of falling and associated morbidity and mortality. We investigated whether endurance training can prevent bone strength decrements in PolG mice. At 3 months of age, 24 PolG mice (♀ = ♂) were randomly assigned to a sedentary (SED) or forced‐endurance training (END; 15m/min for 45 min, 3x/week for 5 months) group. PolG‐SED mice exhibited a marked decrease in maximal load (33%), maximal energy (39%) and stress (33%) vs. wild‐type (WT) controls (P<0.01) with a trend toward decreased stiffness (19%) in the femur (P<0.07) and bone area (9%) at the mid‐diaphysis (P<0.08). PolG‐END showed an improvement in all structural parameters (P<0.01) returning to WT levels. We found no differences in femur length, periosteal and endosteal area at the mid‐diaphysis. Five months of endurance training rescued the loss of femur strength in PolG mice. (Funded by CIHR)