Brain-derived neurotrophic factor (BDNF) is a neuroprotective growth factor that increases in young adults during short, intense bouts of passive heat stress. However, this may not reflect the response in heat-vulnerable populations exposed to air temperatures more consistent with indoor overheating during hot weather and heatwaves, especially as the BDNF response to acute stressors may diminish with increasing age.We therefore evaluated the ambient and body temperature-dependent responses of BDNF inolder adults during daylong passive heating. Sixteenolder adults (6 females; aged 66-78years) completed 8-h exposure to four randomized ambient conditions simulating those experienced indoors during hot weather and heatwaves in continental climates: 22°C (air-conditioning; control), 26°C (health-agency-recommended indoor temperature limit), 31°C, and 36°C (non-airconditioned home); all 45% relative humidity. To further investigate upstream mechanisms of BDNF regulation during thermal strain, we also explored associations between BDNF and circulating heat shock protein 70 (HSP70; taken as an indicator of the heat shock response). Circulating BDNF was elevated by ~ 28% (1139 [95%CI: 166, 2112] pg/mL) at end-exposure in the 36°C compared to the 22°C control condition (P = 0.026; 26°C-and 31°C-22°C differences: P ≥ 0.090), increasing 90 [22, 158] pg/mL per 1°C rise in ambient temperature (linear trend: P = 0.011). BDNF was also positively correlated with mean body temperatures (P = 0.013), which increased 0.12 [0.10, 0.13]°C per 1°C rise in ambient temperature (P < 0.001). By contrast, serum HSP70 did not change across conditions (P ≥ 0.156), nor was it associated with BDNF (P = 0.376). Our findings demonstrate a progressive increase in circulating BDNF during indoor overheating in older adults.
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