Mitochondrial Function and Mitophagy in the Elderly: Effects of Exercise

Abstract

Aging is a natural, multifactorial and multiorganic phenomenon wherein there are gradual physiological and pathological changes over time. Aging has been associated with a decrease of autophagy capacity and mitochondrial functions, such as biogenesis, dynamics, and mitophagy. These processes are essential for the maintenance of mitochondrial structural integrity and, therefore, for cell life, since mitochondrial dysfunction leads to an impairment of energy metabolism and increased production of reactive oxygen species, which consequently trigger mechanisms of cellular senescence and apoptotic cell death. Moreover, reduced mitochondrial function can contribute to age-associated disease phenotypes in model organisms and humans. Literature data show beneficial effects of exercise on the impairment of mitochondrial biogenesis and dynamics and on the decrease in the mitophagic capacity associated to aging. Thus, exercise could have effects on the major cell signaling pathways that are involved in the mitochondria quality and quantity control in the elderly. Although it is known that several exercise protocols are able to modify the activity and turnover of mitochondria, further studies are necessary in order to better identify the mechanisms of interaction between mitochondrial functions, aging, and physical activity, as well as to analyze possible factors influencing these processes.

Irisin and Autophagy: First Update

“…Its beneficial effects on adults’ health has been related also to the induction of autophagy. Recent findings indeed suggested that exercise can induce autophagy in several tissues (e.g., adipose tissue and SkM) and organs (e.g., pancreas, liver, heart, and brain), supporting the evidence that exercise-mediated induction of autophagy could occur at systemic level [ 12 , 13 , 14 ].…”

The Mitochondrial Basis of Aging and Age-Related Disorders

“…Beneficial effects of caloric restriction (CR) in aging retardation have been observed in yeast, flies, worms, mice as well as non-human primates, and recent studies suggest that autophagy is required for lifespan extension by CR in multiple model organisms [ 3 , 211 , 212 , 213 ]. Interestingly, the health benefits of physical exercise partially overlap with CR in terms of improving cellular metabolism, increasing NAD + availability that activates sirtuins, stimulating PGC1α expression, and facilitating mitochondrial quality control [ 214 , 215 , 216 ]. Finally, pharmacological drugs such as rapamycin (mTOR inhibitor) and metformin (AMPK activator) also extend lifespan in model organisms and confer protection against several age-related pathologies [ 217 , 218 ].…”

Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training

“…Mitochondrial remodelling can be conceptualized as a balancing act combining the generation of mitochondria with their dynamic modifications in the network (called fusion/fission), and subsequent clearance through macroautophagy (referred to as mitophagy) . Fusion facilitates ATP synthesis, prevents mitochondrial DNA loss and allows mingling of the organelles .…”

“…While numerous human interventional studies have confirmed the effect of exercise training on key regulators of mitochondria biogenesis in multiple populations, few have explored this effect in fusion and fission, with contradictory results, and none have looked at the effect of an exercise intervention on human muscle mitophagy. The primary aim of this study was to investigate in older adults, markers of mitophagy, fusion and fission using the exact same exercise intervention that increased mitochondrial content and efficiency in human skeletal muscle, focusing on internal validity and using a comprehensive picture of mitochondrial biology from the molecular level to the whole‐body level.…”