Age‐Associated Changes in Autophagy in Peripheral Blood Mononuclear Cells following Maximal Exercise: Preliminary Observations

Abstract

Aging represents the progressive deterioration in the efficacy of cellular survival mechanisms, including the important mechanism of autophagy. Deficiencies in autophagic function, which occur with increasing age, may contribute to the development of many diseases, including neurodegeneration, cardiovascular diseases, and the development of various cancers. Thus, it is imperative to understand the regulation of autophagy in the context of human physiology. Of note, it is suggested that engaging in exercise represents an optimal strategy to improve autophagic function, which may help explain the many health benefits associated with regular exercise. During acute cellular stress, such as exercise, autophagy degrades misfolded or damaged proteins to provide the base constituents (i.e. amino acids) for cellular energy production. Although, until the past decade, few studies have examined the autophagic response to exercise in humans. We have recently demonstrated that exercise‐induced autophagy is intensity‐dependent, with greater intensities required to elicit an increase in autophagic flux, as indicated by elevated levels of microtubule‐associated protein 1 light chain 3 beta (LC3‐II). However, no known studies have evaluated the autophagic response to maximal exercise in humans, and it is unknown if this response is altered by aging. Therefore, we aimed to examine whether autophagy would increase in response to an acute (<15 min) incremental maximal exercise bout in peripheral blood mononuclear cells (PBMCs), and if this response would be altered in older adults. We evaluated the hypothesis that autophagy would increase in response to maximal exercise and that young adults would display greater elevations in autophagy than their older counterparts. To test this hypothesis, PBMCs were collected from 8 young (mean [SD], 20 [2.1] years; 4 women, 4 men) and 8 older (66 [5.5] years; 4 women, 4 men) adults before and immediately after a graded maximal exercise test performed on a semi‐recumbent cycle ergometer. The autophagic marker LC3‐II was assessed by Western blotting, which was normalized to β‐actin (an internal loading control) and reported as a fold change relative to its respective baseline. Data were analyzed using unpaired t‐tests with an alpha set at 0.05. Peak oxygen consumption (VO2peak) was significantly higher in young (41.6 [10.3] ml/kg/min) compared to older (30.3 [6.6] ml/kg/min) adults (p=0.02). Immediately following the maximal exercise bout, an increase in LC3‐II was observed in both young (1.64 [0.45], p=0.005) and older (1.21, [0.24] p=0.048) adults. When comparing between groups, the relative increase in LC3‐II was significantly greater (+27%) in young compared to older adults (p=0.03). Taken together, our preliminary findings show that autophagy is elevated in response to maximal exercise in young and older adults, albeit to a lesser extent in older adults, suggesting an impaired ability to respond to cellular stress. Further research is necessary to understand the mechanisms underlying age‐related impairments in autophagy in older adults and if these responses can be restored.