Markers of enterocyte damage, microbial translocation, and systemic inflammation following 9 h of heat exposure in young and older adults.

Heat stress induced damage to the gastrointestinal barrier can induce local and systemic inflammatory reactions implicated in heat-stroke. Gastrointestinal barrier damage has been shown to be greater in older relative to young adults following hyperthermia. However, comparisons between young and older adults have been limited to brief exposures (3 h), which may not reflect the duration of heat stress experienced during heat waves. We therefore evaluated markers of intestinal epithelial damage (log transformed intestinal fatty acid binding protein, IFABPLOG), microbial translocation (soluble cluster of differentiation 14, sCD14LOG), and systemic inflammation (tumour necrosis factor alpha, TNF-αLOG; interleukin 6, IL-6LOG; C-reactive protein, CRP) in 19 young (interquartile range: 21-27 years; 10 females) and 37 older (68-73 years; 10 females) adults before and after 9 h of rest in 40 °C (9% relative humidity). The magnitude of the increase in IFABPLOG was 0.38 log pg/mL (95% CI, 0.10, 0.65 log pg/mL) greater in the older relative to young cohort (P = 0.049) after 9 h heat exposure. At baseline both IL-6LOG and CRP concentrations were higher in the older (IL-6: 2.67 (1.5) log pg/mL, CRP: 0.28 (1.5) mg/mL) relative to the young (IL-6: 1.59 log pg/mL, SD 1.2; CRP: 0.11 mg/mL, SD 1.7) group (both P ≤ 0.001). The change in IL-6 and CRP was similar between groups following 9 h heat exposure (IL-6: P = 0.053; CRP: P = 0.241). Neither sCD14LOG and TNF-αLOG were different between groups at baseline nor altered after 9 h heat exposure. Our data indicate that age may modify intestinal epithelial injury following 9 h of passive heat exposure.

Elevations in serum brain-derived neurotrophic factor following occupational heat stress are not influenced by age or common chronic disease.

With global warming, workers are increasingly exposed to strenuous occupations in hot environments. Given age- and disease-associated declines in thermoregulatory function, older workers are at an elevated risk of developing heat-related injuries. Brain-derived neurotrophic factor (BDNF) is thought to confer neuroprotection during acute exercise, however, the influence of environmental heat on BDNF responses during prolonged work remains unclear. Therefore, we evaluated serum BDNF concentrations before and after 180 min of moderate-intensity treadmill walking (200 W/m2) and after 60 min of post-exercise recovery in temperate (wet-bulb globe temperature (WBGT) 16°C) and hot (WBGT 32°C) environments in 13 healthy young men (mean [SD; 22 [3] years), 12 healthy older men (59 [4] years), 10 men with hypertension (HTN) (60 [4] years), and 9 men with type 2 diabetes (T2D) (60 [5] years). In the temperate condition, all but one participant (1 HTN) completed the 180 min of exercise. While exercise tolerance in the heat was lower in older men with HTN (117 min [45]) and T2D (123 min [42]) compared to healthy older men (159 min [31]) (both p ≤ 0.049), similar end-exercise rectal temperatures (38.9°C [0.4]) were observed across groups, paralleled by similar elevations in serum BDNF across groups at end-exercise (+1106 pg/mL [203]) and end-recovery (+938 pg/mL [146]; all p ≤ 0.01) in the heat. No changes in serum BDNF were observed in the temperate condition. Our findings indicate similar BDNF responses in individuals with HTN or T2D compared to their healthy counterparts, despite exhibiting reduced tolerance to heat.

Physiological responses to 9 hours of heat exposure in young and older adults. Part II: Autophagy and the acute cellular stress response.

With rising global temperatures, heat-related mortality is increasing, particularly among older adults. Although this is often attributed to declines in thermoregulatory function, little is known regarding the effect of age on the cellular processes associated with mitigating heat-induced cytotoxicity. We compared key components of the cellular stress response in 19 young (19-31 yr; 10 female) and 37 older adults (61-78 yr; 10 female) during 9 h of heat exposure (40°C, 9% relative humidity). Mean body temperature (Tbody) was calculated from core and skin temperatures. Changes in proteins associated with autophagy, apoptotic signaling, acute inflammation, and the heat shock response were assessed via Western blot in peripheral blood mononuclear cells harvested before and after exposure. Tbody increased by 1.5 (SD 0.3)°C and 1.7 (0.3)°C in the young and older adults, respectively. We observed similar elevations in autophagy-related proteins (LC3-II and LC3-II/I) in young and older adults (both P ≥ 0.121). However, the older adults displayed signs of autophagic dysfunction, evidenced by a 3.7-fold [95% CI: 2.4, 5.6] greater elevation in the selective autophagy receptor p62 (P < 0.001). This was paired with elevations in apoptotic responses, with a 1.7-fold [1.3, 2.3] increase in cleaved caspase-3 in the older relative to young adults (P < 0.001). Older adults also exhibited diminished heat shock protein 90 responses (0.7-fold [0.5, 0.9] vs. young, P = 0.011) and, at any given level of thermal strain (Tbody area under the curve), elevated tumor necrosis factor-α (1.5-fold [1.0, 2.5] vs. young, P = 0.008). Attenuated autophagic responses may underlie greater vulnerability to heat-induced cellular injury in older adults.NEW & NOTEWORTHY We demonstrate for the first time that peripheral blood mononuclear cells from older adults exhibit signs of autophagic impairments during daylong (9 h) heat exposure relative to their younger counterparts. This was paired with greater apoptotic signaling and inflammatory responses, and an inability to stimulate components of the heat shock response. Thus, autophagic dysregulation during prolonged heat exposure may contribute to age-related heat vulnerability during hot weather and heat waves.

Impacts of age, diabetes, and hypertension on serum endothelial monocyte-activating polypeptide-II after prolonged work in the heat.

BACKGROUND: With rising temperature extremes, older workers are becoming increasingly vulnerable to heat-related injuries because of age- and disease-associated decrements in thermoregulatory function. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a proinflammatory cytokine that has not yet been well-characterized during heat stress, and which may mediate the inflammatory response to high levels of physiological strain. METHODS: We evaluated serum EMAP-II concentrations before and after 180 min of moderate-intensity work (200 W/m2 ) in temperate (wet-bulb globe temperature [WBGT] 16°C) and hot (WBGT 32°C) environments in heat-unacclimatized, healthy young (n = 13; mean [SD]; 22 [3] years) and older men (n = 12; 59 [4] years), and unacclimatized older men with hypertension (HTN) (n = 10; 60 [4] years) or type 2 diabetes (T2D) (n = 9; 60 [5] years). Core temperature and heart rate were measured continuously. RESULTS: In the hot environment, work tolerance time was lower in older men with HTN and T2D compared to healthy older men (both p < 0.049). While core temperature and heart rate reserve increased significantly (p < 0.001), they did not differ across groups. End-exercise serum EMAP-II concentrations were higher in young men relative to their older counterparts due to higher baseline levels (both p ≤ 0.02). Elevations in serum EMAP-II concentrations were similar between healthy older men and older men with HTN, while serum EMAP-II concentrations did not change in older men with T2D following prolonged work in the heat. CONCLUSION: Serum EMAP-II concentrations increased following prolonged moderate-intensity work in the heat and this response is influenced by age and the presence of HTN or T2D.

Autophagic response to exercise in peripheral blood mononuclear cells from young men is intensity-dependent and is altered by exposure to environmental heat.

Autophagy is essential to maintaining cellular homeostasis in all eukaryotic cells and to tolerance of acute stressors such as starvation, heat, and recovery after exercise. Limited information exists regarding the exercise intensity-dependent autophagic response in humans, and it is unknown how environmental heat stress may modulate this response. Therefore, we evaluated autophagy and accompanying pathways of cellular stress [the heat-shock response (HSR), apoptosis, and acute inflammation] in peripheral blood mononuclear cells (PBMCs) from 10 young men (mean [SD]; 22 [2] years) before, immediately after and up to 6-h postexercise recovery from 30 min of low-, moderate-, and high-intensity semirecumbent cycling [40%, 55%, and 70% of maximal oxygen consumption (V̇o2max), respectively] in a temperate environment (25°C) and at 70% of V̇o2max in a hot environment (40°C). Changes in protein content were analyzed via Western blot. Each increase in exercise intensity was associated with elevations in mean body temperature. LC3-II increased after moderate-intensity exercise, with further increases after high-intensity exercise (P < 0.05). However, an increase in beclin-2 and ULK1, with a decrease in p62 was only observed after high-intensity exercise, which was paralleled by elevated TNF-α and cleaved-caspase-3, with the HSR peaking at 6 h after exercise (P < 0.05). When exercise was performed in the heat, greater LC3-II and cleaved-caspase-3 accumulation were observed; however, beclin-2 declined in recovery (P < 0.05). Therefore, our findings indicate that autophagy in PBMCs during exercise may be associated with greater heat strain exhibited during increasing exercise intensities, which is modulated by exposure to heat.