Manifestations of Age on Autophagy, Mitophagy and Lysosomes in Skeletal Muscle

Triolo, Matthew; Hood, David A.

doi:10.3390/cells10051054

Cited by 32 publications

(24 citation statements)

References 247 publications

(337 reference statements)

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“…Our data also confirm a multitude of reports showing that aging leads to decrements in endurance capacity [ 20 , 39 ]. We further report that young female mice have greater exercise capacity than their male counterparts.…”

Section: Discussionsupporting

confidence: 91%

“…It is well established that regular exercise can counteract the progressive loss of muscle mass and function associated with advancing age [ 36 – 38 ]. This is partially through upregulating the production of healthy cellular components, such as mitochondria, and stimulating the removal of dysfunctional constituents through the autophagy-lysosomes system (i.e., mitophagy) [ 20 , 39 ]. Previous reports from our group have indicated that acute exercise initiates lysosome biogenesis [ 26 ] and that chronic muscle activity elevates lysosome protein content [ 30 , 40 ] in young, healthy muscle.…”

Section: Discussionmentioning

confidence: 99%

“…The impact of aging on skeletal muscle autophagy remains controversial [ 20 ], but previous reports utilizing “flux” measurements have shown that autophagy is upregulated in aging muscle [ 21 , 22 ]. These alterations in autophagy have implications for the selective degradation of mitochondria through mitophagy.…”

Section: Introductionmentioning

confidence: 99%

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The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle

et al. 2022

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Background Aging decreases skeletal muscle mass and quality. Maintenance of healthy muscle is regulated by a balance between protein and organellar synthesis and their degradation. The autophagy-lysosome system is responsible for the selective degradation of protein aggregates and organelles, such as mitochondria (i.e., mitophagy). Little data exist on the independent and combined influence of age, biological sex, and exercise on the autophagy system and lysosome biogenesis. The purpose of this study was to characterize sex differences in autophagy and lysosome biogenesis in young and aged muscle and to determine if acute exercise influences these processes. Methods Young (4–6 months) and aged (22–24 months) male and female mice were assigned to a sedentary or an acute exercise group. Mitochondrial content, the autophagy-lysosome system, and mitophagy were measured via protein analysis. A TFEB-promoter-construct was utilized to examine Tfeb transcription, and nuclear-cytosolic fractions allowed us to examine TFEB localization in sedentary and exercised muscle with age and sex. Results Our results indicate that female mice, both young and old, had more mitochondrial protein than age-matched males. However, mitochondria in the muscle of females had a reduced respiratory capacity. Mitochondrial content was only reduced with age in the male cohort. Young female mice had a greater abundance of autophagy, mitophagy, and lysosome proteins than young males; however, increases were evident with age irrespective of sex. Young sedentary female mice had indices of greater autophagosomal turnover than male counterparts. Exhaustive exercise was able to stimulate autophagic clearance solely in young male mice. Similarly, nuclear TFEB protein was enhanced to a greater extent in young male, compared to young female mice following exercise, but no changes were observed in aged mice. Finally, TFEB-promoter activity was upregulated following exercise in both young and aged muscle. Conclusions The present study demonstrates that biological sex influences mitochondrial homeostasis, the autophagy-lysosome system, and mitophagy in skeletal muscle with age. Furthermore, our data suggest that young male mice have a more profound ability to activate these processes with exercise than in the other groups. Ultimately, this may contribute to a greater remodeling of muscle in response to exercise training in males.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle

et al. 2022

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“…Autophagy is activated under nutrient deprivation. Antimicrobial peptide-activated protein kinase (AMPK) inhibits the mTOR complex-1 (mTORC1) complex, which in turn inhibits protein synthesis, and can even lead to severe late-onset myopathy ( 31 , 32 ). The studies demonstrate that autophagy plays an important role in skeletal muscle atrophy.…”

Section: Molecular Mechanisms Of Skeletal Muscle Atrophymentioning

confidence: 99%

Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies

Shen

Wang

et al. 2022

Front. Endocrinol.

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Diabetes mellitus (DM) is a typical chronic disease that can be divided into 2 types, dependent on insulin deficiency or insulin resistance. Incidences of diabetic complications gradually increase as the disease progresses. Studies in diabetes complications have mostly focused on kidney and cardiovascular diseases, as well as neuropathy. However, DM can also cause skeletal muscle atrophy. Diabetic muscular atrophy is an unrecognized diabetic complication that can lead to quadriplegia in severe cases, seriously impacting patients’ quality of life. In this review, we first identify the main molecular mechanisms of muscle atrophy from the aspects of protein degradation and synthesis signaling pathways. Then, we discuss the molecular regulatory mechanisms of diabetic muscular atrophy, and outline potential drugs and treatments in terms of insulin resistance, insulin deficiency, inflammation, oxidative stress, glucocorticoids, and other factors. It is worth noting that inflammation and oxidative stress are closely related to insulin resistance and insulin deficiency in diabetic muscular atrophy. Regulating inflammation and oxidative stress may represent another very important way to treat diabetic muscular atrophy, in addition to controlling insulin signaling. Understanding the molecular regulatory mechanism of diabetic muscular atrophy could help to reveal new treatment strategies.

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“…In fact, NOX2-dependent ROS signaling activates lysosomes and autophagic flux, but excess ROS can inhibit autophagy and impact muscle mass and function (48). Through this axis, alterations in autophagy due to aging could contribute to muscle deficits through diminished hypertrophic program activation (119)(120)(121).…”

Section: Musculoskeletal Aging: Problems With Age Related Cellular St...mentioning

confidence: 99%

Aging, Osteo-Sarcopenia, and Musculoskeletal Mechano-Transduction

Leser¹,

Harriot²,

Buck³

et al. 2021

Front. Rehabilit. Sci.

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The decline in the mass and function of bone and muscle is an inevitable consequence of healthy aging with early onset and accelerated decline in those with chronic disease. Termed osteo-sarcopenia, this condition predisposes the decreased activity, falls, low-energy fractures, and increased risk of co-morbid disease that leads to musculoskeletal frailty. The biology of osteo-sarcopenia is most understood in the context of systemic neuro-endocrine and immune/inflammatory alterations that drive inflammation, oxidative stress, reduced autophagy, and cellular senescence in the bone and muscle. Here we integrate these concepts to our growing understanding of how bone and muscle senses, responds and adapts to mechanical load. We propose that age-related alterations in cytoskeletal mechanics alter load-sensing and mechano-transduction in bone osteocytes and muscle fibers which underscores osteo-sarcopenia. Lastly, we examine the evidence for exercise as an effective countermeasure to osteo-sarcopenia.

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Manifestations of Age on Autophagy, Mitophagy and Lysosomes in Skeletal Muscle

Cited by 32 publications

References 247 publications

The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle

The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle

Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies

Aging, Osteo-Sarcopenia, and Musculoskeletal Mechano-Transduction

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