Seven days of warm-water immersion enhances resting irisin and BDNF, but not klotho, in older men

We examined whether seven consecutive days of warm-water immersion could elevate resting and exercise-induced levels of brain-derived neurotrophic factor (BDNF), irisin and klotho in older adults. These biomarkers support cognitive and metabolic health, but their levels decline with age. Passive heat exposure, like warm-water immersion, may offer a promising alternative to exercise for enhancing cellular-level physiological resilience in populations where exercise is limited. Twelve habitually active older men (median [IQR] age: 68 [64-73] years; ${\dot{V}}_{O_2\mathrm{peak}}$ : 34.1 [29.4-36.1] mL O₂ · kg^{- 1} · min^{- 1}) completed seven consecutive days of ∼90-min warm-water immersion (∼40°C), with rectal temperature maintained at ∼38.5°C for the final 60 min. Before and after the warm-water immersion intervention, participants completed a standardized exercise-heat stress test consisting of three 30-min cycling bouts (150, 200 and 250 W · m^{- 2}), each separated by 15-min rest. Blood samples were collected at baseline and post-exercise to assess circulating BDNF, irisin, and klotho. Repeated warm-water immersion increased resting BDNF by 2.43 ng · mL^-1 (95% CI: 0.64-4.23; P = 0.005; 1.73-fold) and irisin by 0.94 ng · mL^-1 (95% CI: 0.25-1.63; P = 0.005; 1.65-fold). Resting klotho concentration did not change (mean difference: +0.05 ng · mL^-1; 95% CI: -0.05 to 0.14; P = 0.539). No significant exercise-induced changes in any cytoprotective hormones were observed (P ≥ 0.053). Seven consecutive days of warm-water immersion elevated resting levels of BDNF and irisin, but not klotho, in older males. Passive heat acclimation may offer a non-exercise strategy to upregulate biomarkers linked to cognitive and metabolic health, reflecting activation of cellular pathways associated with physiological resilience.