Late‐In‐Life Treadmill‐Training Ameliorates the Decline in Cardiac Autophagy Associated with Aging in Mice

Abstract

Protein aggregates accumulate and organelles become damaged and/or dysfunctional during the process of aging. A progressive loss of the cellular quality control mechanism autophagy contributes to this age‐associated decline in cellular function in many organs. Evidence for an age‐associated repression in cardiac autophagy is not consistent. We hypothesized that 24‐month old (old) male C57Bl6/J mice exhibit repressed autophagosome formation in the heart, myocardial dysfunction, and reduced exercise capacity vs. 6‐month old (adult) mice. First, cardiac lysates from old mice displayed reduced (p<0.05) accumulation of LC3II/GAPDH and degradation of p62 vs. adult animals (n=12 per group). Second, the lysosomal acidification inhibitor chloroquine (CQ) induced accrual (p<0.05) of LC3II/GAPDH and p62 in hearts from adult but not old mice (n=7 per group). Third, left ventricular mass was greater (p<0.05), and indices of systolic, diastolic, and global left ventricular function (transthoracic echocardiography) were impaired, in old vs. adult animals (n=12 per group). Finally, maximal workload performed during a treadmill‐test was less (p<0.05) in aged (n=11) vs. adult (n=12) mice. To determine whether late‐in‐life exercise training induces cardiac autophagy, separate cohorts of male mice completed a progressive‐resistance treadmill‐running program (old‐ETR) or remained sedentary (old‐SED) from 21–24 months. Body composition, exercise performance during a maximal workload test, soleus muscle citrate synthase (CS) activity, indices of cardiac antioxidant enzyme activity, markers of cardiac autophagy, and indices of myocardial function, all improved (p<0.05) in old‐ETR (n=11) vs. old‐SED (n=12) mice. These data are the first to demonstrate that markers of cardiac autophagy are elevated, and indices of myocardial function are improved, in old mice that complete a treadmill‐training regimen that is sufficient to increase skeletal muscle CS activity and maximal exercise capacity. These data provide strong proof of concept to evaluate cause and effect relationships among exercise‐training, myocardial.Support or Funding InformationUU Research Fellowship (JMC); APS UGRF (CR); AHA17POST33670663 (SKP); NIHRO1DK098646‐01A1, NIHRO1DK099110, AHA16GRANT30990018 (SB); AHA16GRNT31050004, NIH RO3AGO52848, NIH RO1HL141540 (JDS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.