Short-term passive heat acclimation modulates autophagy and cellular stress responses in older active adults

Age-related impairments in thermoregulatory and cardiovascular function contribute to a heightened vulnerability to heat-related morbidity and mortality. While passive heat acclimation is highly effective at improving heat loss mechanisms in older adults, its effects on autophagic regulation remain unknown. Given autophagy represents a critical cellular survival mechanism and declines with advancing age, we sought to assess whether short-term passive heat acclimation via warm-water immersion modulates autophagic regulation and accompanying cellular stress pathways in older adults.

Twelve healthy older males (median interquartile range (IQR): 68 (64‒73) years) completed 7 days of passive heat acclimation via warm-water immersion (∼40°C), with core temperature maintained at 38.5°C for 60 min. Before and after acclimation, participants completed an exercise-heat stress test in 40°C (∼13% relative humidity) consisting of three 30-min cycling bouts (150, 200, and 250 W/m²), each separated by 15-min rest. Changes in protein content and gene expression were assessed in peripheral blood mononuclear cells (PBMC) before and after each exercise-heat stress test, as well as Days 1, 4, and 7 of the acclimation protocol.

Across acclimation days, microtubule-associated light chain 3B (LC3)-II, LC3-II/I ratio, and lysosome-associated membrane protein-2A proteins progressively increased (p ≤ 0.019), while sequestosome-1/p62 decreased (p = 0.003), consistent with enhanced autophagic activity. Conversely, apoptotic-related cleaved-caspase-3 progressively declined with acclimation (p = 0.004). Post-acclimation exercise-heat stress responses elicited greater elevations in protein and gene markers of autophagy, as well as reduced apoptotic responses.

Short-term passive heat acclimation increased PBMC markers associated with autophagy while reducing markers of apoptotic signaling in healthy, active older males.