Physiological responses to 9 hours of heat exposure in young and older adults. Part II: Autophagy and the acute cellular stress response

Abstract

With rising global temperatures, heat-related mortality is increasing, particularly among older adults. While this is often attributed to declines in thermoregulatory function, little is known regarding the effect of age on the cellular processes associated with mitigating heat-induced cytotoxicity. We compared key components of the cellular stress response in 19 young (19-31 years; 10 female) and 37 older adults (61-78 years; 10 female) during 9 hours of heat exposure (40°C, 9% relative humidity). Mean body temperature (Tbody) was calculated from core and skin temperatures. Changes in proteins associated with autophagy, apoptotic signaling, acute inflammation, and the heat shock response were assessed via Western blot in peripheral blood mononuclear cells harvested before and after exposure. Tbody increased 1.5 (SD 0.3)°C and 1.7 (0.3)°C in the young and older adults, respectively. We observed similar elevations in autophagy-related proteins (LC3-II and LC3-II/I) between young and older adults (both P≥0.121). However, the older adults displayed signs of autophagic dysfunction, evidenced by a 3.7-fold [95% CI: 2.4, 5.6] greater elevation in the selective autophagy receptor p62 (P<0.001). This was paired with elevations in apoptotic responses, with a 1.7-fold [1.3, 2.3] increase in cleaved caspase-3 in the older relative to young adults (P<0.001). Older adults also exhibited diminished heat shock protein 90 responses (0.7-fold [0.5, 0.9] vs young, P=0.011) and, at any given level of thermal strain (Tbody area under the curve), elevated tumor necrosis factor-α (1.5-fold [1.0, 2.5] vs young, P=0.008). Attenuated autophagic responses may underlie greater vulnerability to heat-induced cellular injury in older adults.

Effects of Daylong Exposure to Indoor Overheating on Thermal and Cardiovascular Strain in Older Adults: A Randomized Crossover Trial

“…Supporting this postulate, we recently observed that although type 2 diabetes is associated with reduced heat loss during moderate exercise in the heat, 96 physiological responses did not differ between older adults with or without well-controlled type 2 diabetes during a resting 3-h exposure to 44°C and 35% relative humidity 97 conditions exceeding those measured indoors during heat waves. 20 , 21 , 34 Likewise, we recently showed no differences in body temperature 98 or cellular strain 99 between older adults with and without well-controlled type 2 diabetes and/or hypertension during 9-h of exposure to 40°C, 9% relative humidity. Furthermore, although maintaining high levels of aerobic fitness has been shown to prevent the age-related decline in thermoregulatory function during exercise heat-stress, these effects are considerably reduced at lower levels of heat stress like those that might be experienced by vulnerable groups indoors during hot weather.…”