Treadmill Training for Old Mice Upregulates Autophagy and Improves Heart Function
It is well demonstrated that structured exercise programs improve function and reduce mortality in old humans, in part because the majority of people do not undertake anywhere near enough exercise. For mice, more activity takes place into later life, but how much is quite dependent on the environment in which they are housed. Looking at the study here, I would expect this to be a comparison of exercise trained mice with untrained mice that are less active than they would be if given options such as an exercise wheel. That may be a better match to the human situation than the other options. While looking at the results, it is worth recalling that past data shows that exercise interventions improve healthspan but not lifespan in mice. It isn't as effective as calorie restriction in this regard.
Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late-in-life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs. adult mice.
As expected, 24-month-old male C57BL/6J mice (old) exhibited repressed autophagosome formation and protein aggregate accumulation in the heart, systolic and diastolic dysfunction, and reduced exercise capacity vs. 8-month-old (adult) mice. To investigate the influence of late-in-life exercise training, additional cohorts of 21-month-old mice did (old-ETR) or did not (old-SED) complete a 3-month progressive resistance treadmill running program. Body composition, exercise capacity, and soleus muscle citrate synthase activity improved in old-ETR vs. old-SED mice at 24 months. Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced in hearts from old-ETR vs. old-SED mice.
This data provides the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts.