Regional variation in age-related decline of acetylcholine-induced sweating in the forearm and lower limb: an exploratory study in males

It remains unclear how progressive aging alters regional differences in cholinergic sweat gland function across forearm and lower limb sites. We assessed acetylcholine-induced sweating in 52 healthy males aged 19-69 years, grouped by decade: 20s (n = 19, 21 ± 1 years), 40s (n = 12, 43 ± 3 years), 50s (n = 10, 53 ± 1 years), and 60s (n = 11, 66 ± 3 years). Sweat rate, activated sweat gland density, and sweat gland output were measured via transdermal iontophoresis at the volar forearm, anterior and posterior thigh, anterior and posterior lower leg, and dorsal foot. Sweat rate at the forearm and foot did not differ significantly across age groups (all P ≥ 0.077). However, thigh sweat rate declined with age: reductions were observed in the posterior thigh from the 50s (P ≤ 0.004) and in the anterior thigh in the 60s (P ≤ 0.036). The lower leg showed earlier declines, with reduced sweat rate evident from the 40s on the posterior side (all P ≤ 0.003) and from the 50s on the anterior side (both P ≤ 0.002). These reductions were primarily attributable to decreases in sweat gland output, rather than changes in activated sweat gland density. In conclusion, this exploratory study suggests that male cholinergic sweat gland function may exhibit region-specific, age-related decline across the forearm and the lower limbs. The posterior lower leg appears most susceptible, with reductions evident in the 40s, while the anterior thigh shows relatively preserved function until the 60s. Future hypothesis-driven studies, including females, are warranted to confirm these observations.