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 (all p < 0.05). 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 (all p < 0.05). Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced (all p < 0.05) in hearts from old‐ETR vs. old‐SED mice. These data provide the first evidence that a physiological intervention initiated late‐in‐life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts.

Introduction This study explores perceived stress and experience with bruxism among veterans with Gulf War Illness (GWI). Stress may manifest physically as bruxism, a parafunctional oral activity that consists of teeth grinding and/or clenching. Materials and Methods An online survey of GWI veterans (n = 28, 27.7% response rate) assessed perceived general stress and self-reported behaviors, symptoms, and outcomes associated with bruxism. Survey questions also collected basic demographic data and past military experience. The appropriate Institutional Review Board approved this study (IRB-300001376). Statistical analyses utilized both analysis of variance and linear regression techniques in addition to descriptive statistics. Results This sample of GWI veterans reported higher levels of perceived stress (M = 20.2, SD = 7.0) than general population males (M = 12.1, SD = 5.9). A majority of GWI veterans reported both grinding (77.8%) and clenching (85.2%) teeth on a weekly or daily basis. Grinding frequency did not predict perceived stress scale values (F = 2.38, P = .11). Clenching frequency did significantly predict perceived stress scale values (F = 4.07, P = .03). Those who reported daily clenching had significantly higher perceived stress scores (M = 22.17, SD = 5.87) than did those who reported never clenching (M = 12.00, SD = 5.35). Length of military service did not significantly predict perceived stress or bruxism experience. Conclusions GWI veterans reported higher levels of perceived stress in comparison with that of general population males. Both the high frequency of teeth grinding and clenching in these patients is a potential physical manifestation of the high perceived stress levels reported. It is imperative that both military and civilian dentists and physicians are aware of the potential for increased stress and consequently bruxism in this patient population as it can have negative impacts on oral and mental health. Treatment of these patients can include but is not limited to behavior modification, stress reduction training, and the fabrication of mouth guards. The dental and medical implications of bruxism and stress in veterans with GWI should be further investigated.

There is evidence for a progressive decline of protein quality control mechanisms during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy (referred to as autophagy) 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 : (i) repressed autophagosome formation and protein aggregate accumulation in the heart; (ii) systolic and diastolic dysfunction; and (iii) reduced exercise capacity, vs. 8-month old (adult) mice (all p< .05). Separate cohorts of 21 month old mice completed a 3-month progressive resistance treadmill-running program (old-ETR) that improved (all < .05) : (i) body composition; (ii) exercise capacity; and (iii) soleus muscle citrate synthase activity, vs. age-matched mice that did not train (old-SED). Importantly, (iv) protein expression of autophagy markers indicated trafficking of the autophagosome to the lysosome increased, (v) protein aggregate clearance improved, and (vi) overall function was enhanced (all p<0.05), in hearts from old-ETR vs. old-SED mice. Dietary maneuvers and pharmacological interventions shown to elevate basal autophagy are reported to mitigate / reverse age-associated cardiac dysfunction. Here we show the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and overall function in mouse hearts.

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.