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

Abstract

AbstractAutophagy 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 3 h 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.