Effects of 24-h sleep deprivation on circulating irisin, BDNF, and soluble klotho responses during exercise in the heat in young and older males

Sleep deprivation and heat stress commonly coexist in occupational, athletic, and environmental settings and may disproportionately increase physiological strain in older adults. We examined whether 24-h sleep deprivation alters circulating biomarkers linked to proposed roles in metabolic adaptation (irisin), neurophysiological regulation (BDNF), and cellular stress protection (soluble klotho) during exercise in the heat in young and older males. Ten young (23±3 years) and ten older (61±4 years) males completed randomized crossover trials involving normal sleep and 24-h total sleep deprivation before three 30-min bouts of semi-recumbent cycling in hot, dry conditions (40°C, ∼13% relative humidity). Blood samples were obtained before and at end-exercise for measurement of irisin, BDNF, and soluble klotho (s-klotho). Older males exhibited lower circulating concentrations of all three biomarkers across conditions and time points than young males. Exercise in the heat increased irisin (mean change 522.7 pg/mL, 95% CI 310.6 to 734.8, p<0.001, q<0.001), whereas no statistically significant overall pre-to-end change was observed for BDNF or s-klotho. The irisin response appeared smaller in older than young males when averaged across sleep conditions (between-group difference 458.1 pg/mL, 95% CI 34.0 to 882.3, p=0.035) but did not remain significant after correction across the three age × time contrasts (q=0.104) and is therefore hypothesis-generating. However, the study did not detect evidence that 24-h sleep deprivation altered circulating irisin, BDNF, or s-klotho responses in either age group. These findings demonstrate age-related differences in circulating biomarker concentrations, but do not establish corresponding differences in physiological adaptability or biomarker responsiveness.