Age-related differences in gene expression and pathway activation following heat stroke.

Abstract

This study investigates the molecular responses to heat stroke in young and old patients by comparing whole-genome transcriptomes between age groups. We analyzed transcriptomic profiles from patients categorized into two age-defined cohorts: young (mean age = 44.9 ± 6 years) and old (mean age = 66.1 ± 4 years). Control subjects, exposed to similar environmental heat conditions but without developing heat stroke, were also included in the analysis to provide a baseline for comparison. Despite uniform heat stroke severity at admission, as indicated by core body temperature, consciousness level, and organ damage markers, notable gene expression differences emerged. Old patients showed 37% fewer differentially expressed genes compared to young patients at admission, with a shift towards gene upregulation, deviating from the usual downregulation seen in heat stress responses. Both age groups exhibited increased heat shock protein gene expression, activated the heat stress and unfolded protein responses indicating comparable proteotoxic stress. Nonetheless, age-specific differences were evident in critical regulatory pathways like Sirtuin, mTOR, and p53 signaling, along with key pathways related to proteostasis, energy metabolism, oxidative stress, and immune responses. Following cooling, older adults exhibited a decline in the heat stress response and a cessation of the unfolded protein response, in contrast to the sustained responses seen in younger individuals. This pattern suggests an age-related adaptability or a diminished protective response capacity with aging. These findings provide insights into the biological mechanisms that may contribute to age-specific vulnerabilities to heat.