Effect of daylong exposure to indoor overheating on autophagy and the cellular stress response in older adults

To protect vulnerable populations during heat waves, public health agencies recommend maintaining indoor air temperature below similar to 24-28 degrees C. While we recently demonstrated that maintaining indoor temperatures <= 26 degrees C mitigates the development of hyperthermia and cardiovascular strain in older adults, the cellular consequences of prolonged indoor heat stress are poorly understood. We therefore evaluated the cellular stress response in 16 adults (six females) aged 66-78 years during 8 h rest in ambient conditions simulating homes maintained at 22 degrees C (control) and 26 degrees C (indoor temperature upper limit proposed by health agencies), as well as non-air-conditioned domiciles during hot weather and heat waves (31 and 36 degrees C, respectively; all 45% relative humidity). Western blot analysis was used to assess changes in proteins associated with the cellular stress response (autophagy, apoptosis, acute inflammation, and heat shock proteins) in peripheral blood mononuclear cells harvested prior to and following exposure. Following 8 h exposure, no cellular stress response -related proteins differed significantly between the 26 and 22 degrees Cconditions (all, P >= 0.056). By contrast, autophagy-related proteins were elevated following exposure to 31 degrees C (p62: 1.5 -fold; P = 0.003) and 36 degrees C (LC3-II, LC3-II/I, p62; all >= 2.0 -fold; P <= 0.002) compared to 22 degrees C. These responses were accompanied by elevations in apoptotic signaling in the 31 and 36 degrees C conditions (cleaved-caspase-3: 1.8-fold and 3.7-fold, respectively; P <= 0.002). Furthermore, HSP90 was significantly reduced in the 36 degrees C compared to 22 degrees C condition (0.7-fold; P = 0.014). Our findings show that older adults experience considerable cellular stress during prolonged exposure to elevated ambient temperatures and support recommendations to maintain indoor temperatures <= 26 degrees C to prevent physiological strain in heat -vulnerable persons.