Temperature-Dependent Relationship of Autophagy and Apoptotic Signaling During Cold-Water Immersion in Young and Older Males.

Abstract

Autophagy is a crucial cytoprotective mechanism preventing the accumulation of cellular damage, especially during external stimuli such as cold exposure. Older adults poorly tolerate cold exposure and age-related impairments in autophagy may contribute to the associated reductions in cold tolerance. The purpose of this investigation is to evaluate the effect of different intensities of in vivo cold-water immersion and in vitro cold exposure on autophagic and apoptotic signaling in young and older males. Peripheral blood mononuclear cells (PBMCs) are isolated at baseline, end-cold exposure, and after 3h of thermoneutral recovery. Additionally, PBMCs are treated with rapamycin and bafilomycin prior to in vitro cold exposure equivalent to in vivo core temperatures (35-37°C). Proteins associated with autophagy, apoptosis, the heat shock response, and inflammation are analyzed via Western blotting. Moderate cold stress (0.5°C decrease in core temperature) increased autophagic and heat shock protein activity while high cold stress (1.0°C decrease in core temperature) augmented apoptosis in young males. In older males, minimal autophagic activation during both cold-water exposures are associated with increased apoptotic and inflammatory proteins. Although in vitro cold exposure confirmed age-related dysfunction in autophagy, rapamycin-induced stimulation of autophagic proteins underlie the potential to reverse age-related vulnerability to cold exposure.