Select articles on autophagy and cellular physiology of exercise relating to human function, health, and training adaptations.
"Diet and exercise will help you live longer":
The meme that turns on housekeeping genes
Advances in Geriatric Medicine and Research, 2(1), e200002. doi:10.20900/agmr20200002
Humans evolved under conditions of high physical activity and periodic privation which shaped our genes and explains why "exercise is medicine". The human body is used to physical and energetic stress rather than physical inactivity and caloric excess. During times of energetic challenge autophagy would have been stimulated to provide energy through the degradation of intracellular components and aided in survival. Exercise and caloric restriction can upregulate autophagy and appears to be involved in their beneficial outcomes. This article discusses how the origins of the well-known meme, “Diet and exercise will help you live longer” span back to our evolutionary environment while its effects extend into our intracellular environment
Autophagy and aging: Maintaining the proteome through exercise and caloric restriction
​
Maintenance of the intracellular environment is key to tissue function and health. Accumulation of damaged and dysfunctional proteins, organelles, and mitochondria are related to chronic and age-related disease. Autophagy acts to degrade cellular components and can be upregulated with exercise and caloric restriction. However, autophagy appears to decline with age. This article discusses the relationship between autophagy, mTOR, exercise, and caloric restriction on aging.
​
Autophagy response to acute high-intensity interval training and moderate-intensity continuous training is dissimilar in skeletal muscle and peripheral blood mononuclear cells and is influenced by sex
Human Nutrition & Metabolism, 23. https://doi.org/ 10.1016/j.hnm.2020.200118
Much of the research on autophagy and exercise has studied continuous aerobic training with some data on resistance training. These studies have also only measures autophagy in one tissue, skeletal muscle or white blood cells (PBMCs). Our study investigated the effects of HIIT on autophagy compared to continuous aerobic exercise in both skeletal muscle and PBMCs. We showed both HIIT and continuous exercise caused changes in autophagy with continuous exercise appearing to alter autophagy to a greater degree. This study also showed autophagy responses are different in skeletal muscle and PBMCs and may also be affected by sex. These
Effect of heat stress on heat shock protein expression and hypertrophy-related signaling in the skeletal muscle of trained individuals
Muscle mass is balanced between hypertrophy and atrophy by cellular processes, including mTOR and other hypertrophy signaling pathways. Stressors apart from exercise and nutrition, such as heat stress, can stimulate the heat shock proteins alongside hypertrophic signaling factors and muscle growth. The effects of heat stress on heat shock protein expression and Akt-mTOR activation in human skeletal muscle and their magnitude of activation compared with known hypertrophic stimuli are unclear. Here, we show a single session of whole body heat stress following resistance exercise increases the expression of HSPA and activation of the Akt-mTOR cascade in skeletal muscle compared with resistance exercise in a healthy, resistance-trained population. We also showed heat stress in cultured muscle cells also promotes growth.
The biphasic activity of autophagy and heat shock protein response in peripheral blood mononuclear cells following acute resistance exercise in resistance-trained males
​
European Journal of Applied Physiology, https://doi.org/10.1007/s00421-024-05503-5
Autophagy and the heat shock protein (HSP) response are two proteostatic systems that work to maintain the cellular proteome where autophagy degrades and recycles proteins while HSP repairs them. Both have been shown to be upregulated with acute exercise and are implicated in the positive adaptations to exercise. It has been hypothesized by a mentor of mine, Dr. Karol Dokladny, that these two systems may work in a coordinated fashion in response to cellular stress whereby autophagy is upregulated in the initial phase of the post-stress period and HSP in the latter with HSP acting as a negative regulator of autophagy. However, very few human data exist and none looking at proteostatic responses as far out as three days. In this study, we assessed the effects of acute intense resistance training with and without branched-chain amino acid (BCAA) supplementation on autophagy and HSP activity immediately post-exercise up to 72 hours post in white blood cells. Our results were consistent with Karol's hypothesized model in that autophagy was upregulated in the initial hours up to 24 hours followed by an upregulation of HSP 48 and 72 hours post-exercise. Moreover, this response was observed in a distal tissue (i.e. not skeletal muscle), suggesting a systemic proteostatic response. Additionally, there was no effect of BCAA supplementation. These data suggest that theses two proteostatic systems function in a coordinated fashion in response to acute stress and that resistance training elicits a systemic protoeostatic response that may be involved in the whole body benefits of resistance exercise.
Other related publications
​
​
Book chapters
​
Articles in preparation or review
​
Biphasic relationship of autophagy and heat shock response in peripheral blood mononuclear cells following an acute bout of eccentric resistance exercise
​
The effect of moderate intensity exercise in hypobaric hypoxia on markers of autophagy and angiogenesis
​
