The efficacy of fan use on autophagy and the cellular stress response during prolonged exposure to extreme heat in older adults: a randomized trial

Recent guidance has advocated the use of electric fans as a simple and sustainable cooling strategy to safeguard older adults during exposure to extreme heat. While we showed that fans have negligible impacts on core temperature during daylong (8 h) heat exposure (36 °C, 45% relative humidity (RH)), their impact on cellular responses and potential contribution to heat-induced cellular vulnerability in older adults remains unknown. We assessed 18 participants (8 females, median age 72 (IQR, 67-76) years) exposed to three heat exposures (8 h, 36 °C, 45% RH) with either no fan (control), or with fans generating air speeds of 2 m/s, or 4 m/s directed at the front of the body. Rectal temperature was measured continuously, while proteins associated with autophagy, the heat shock response, acute inflammation, and apoptotic signaling were measured before and after each exposure in peripheral blood mononuclear cells. We observed signs of autophagic dysfunction as indexed via elevations in p62 and pULK1/ULK1 from baseline in each condition; however, responses were not different between conditions (<i>p</i> ≥ 0.077). Further, while fan use did not alleviate elevations in rectal temperature or prevent observations of autophagic dysfunction compared to control, fan use at 4 m/s elicited significant elevations in apoptotic protein cleaved-caspase-3 (mean difference: +0.69 relative quantity, <i>p</i> = 0.033), potentially attributed to elevated serum osmolality (+2.6 mOsm/L, <i>p</i> = 0.020). Therefore, fan use at high settings during heatwaves may be ineffective at alleviating autophagic dysfunction and can potentially incur greater cellular stress in older adults. ClinicalTrials.gov identifier NCT05695079.