The Effect Of Exercise- And Passive-induced Heat Stress On The Autophagic Response In Older Adults

Autophagy is vital for cell survival during acute physiological and environmental stress through the breakdown of damaged cellular constituents. In recent work, we showed that autophagy is activated in an intensity-dependent manner during aerobic exercise and passive heat stress in young adults, although older adults exhibit impaired heat-induced autophagic regulation. However, differences in autophagic activation associated with elevations in core temperature (Tco) induced by a passive (non-metabolic) and exercise-induced (metabolic) heat load remain unclear. PURPOSE: To assess the effect of equivalent elevations in Tco induced through exercise and warm-water immersion (WI) on autophagy in older males. METHODS: Nine older males (mean [SD] 70 [5] years) performed 30 min of vigorous semi-recumbent cycling at 70% of their pre-determined maximal oxygen consumption. Thereafter, on a separate day, participants were immersed to the clavicle in warm water for 30 min, with water temperature adjusted to induce an increase in Tco (indexed by rectal temperature) comparable to exercise. Proteins associated with autophagic activity (light chain 3 beta [LC3-II]) and autophagic initiation (Unc-51-like kinase 1 [ULK1]) were assessed before and after each respective exposure (exercise or WI) and during a 6-hour seated recovery in a temperate environment (~22 °C). Data were normalized to β-actin (expressed as a relative quantity [RQ] from baseline) and analyzed via a two-way repeated measures ANOVA with Bonferroni test (α=0.05). RESULTS: Tco increased similarly after 30-min (+0.77 [0.27] and +0.78 [0.35]°C, respectively; p=0.90) in both conditions, with both returning to baseline after 3 hours. End-exercise LC3-II was significantly higher than end-WI (2.43 RQ [0.97] vs 0.97 [0.52], respectively; p=0.01), as well as following 3h (3.38 RQ [2.15] vs 0.88 [0.49], respectively; p=0.02) and 6 h (3.86 RQ [3.00] vs 0.78 [0.44], respectively; p=0.02) of recovery. Conversely, ULK1 increased in response to exercise and WI, and remained elevated throughout the 6h recovery (time main effect: p=0.03). CONCLUSION: We showed that despite comparable elevations in autophagic initiation, exercise elicits greater activation of autophagy when compared to an equivalent increase in Tco induced by a passive heat stress in older males. Natural Sciences and Engineering Research Council of Canada and Mitacs