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<\/strong>\nPurpose: With the advent of climate change, older adults are increasingly exposed to hot ambient temperatures that can lead to a state of heat-induced cytotoxicity contributing to heat-vulnerability. We assessed changes in serum proteins associated with indices of cellular stress in young and older adults exposed to extreme passive heat exposure.<\/p>\n
Methods:<\/strong> Responses were assessed in 19 young (23 \u00b1 2.9 years; 5 female) and 27 older (62 \u00b1 7.0 years; 2 female) adults exposed to a 3-h seated passive extreme heat exposure (44 \u00b0C, 30% relative humidity). Serum samples were assessed before and after heat exposure for proteins indicative of systemic inflammation (CRP, sCD14, TNF-\u03b1, and IL-6), intestinal permeability (IFABP), acute kidney injury (NGAL), and cytoprotection (irisin, klotho, and HSP70) via enzyme-linked immunosorbent assays.<\/p>\n Results:<\/strong> The older group displayed significant elevations in CRP (18.06 \u00b1 20.3 vs 24.3 \u00b1 25.0 mg\/mL, p < 0.002) in response to heat exposure that was not observed in the young group (both p > 0.999) although no changes in sCD14, TNF-\u03b1, or IL-6 occurred in either group. However, significant elevations in NGAL concentrations from baseline were observed in the older group (17.74 \u00b1 23.65 vs 40.75 \u00b1 58.18 ng\/mL, p = 0.001), with no changes from baseline in the young group (p = 0.999). Conversely, klotho was significantly elevated after heat exposure in the young group (1346.37 \u00b1 2242.49 vs 1129 \u00b1 202 pg\/mL, p = 0.017) but not in older adults (p > 0.999).<\/p>\n Conclusion:<\/strong> Taken together, older adults experienced some evidence of elevated inflammatory signaling and acute kidney injury that is accompanied by a blunted klotho response to extreme heat.<\/p>\n