Autophagic Signaling and Proteolytic Enzyme Activity in Cardiac and Skeletal Muscle of Spontaneously Hypertensive Rats following Chronic Aerobic Exercise

McMillan, Elliott M.; Paré, Marie-France; Baechler, Brittany L.; Graham, Drew A.; Rush, James W. E.; Quadrilatero, Joe

doi:10.1371/journal.pone.0119382

Cited by 41 publications

(33 citation statements)

References 66 publications

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“…The same study found no changes to Atrogin-1 expression [100]. Protein amounts of MuRF1 and Atrogin-1 (that were not quantified in the present study) were recently shown to remain stable after 6 weeks of treadmill activity (5 days/week) when measured in the gastrocnemius muscles of male Wistar Kyoto rats at 11 weeks of age [101]. Thus, it appears that key markers of proteasomal degradation are relatively unaffected in both human and rodent muscles in response to chronic forms of exercise training.…”

Section: Discussionmentioning

confidence: 54%

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

et al. 2016

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BackgroundThere is much interest in the capacity of resistance exercise to prevent the age-related loss of skeletal muscle mass and function, known as sarcopenia. This study investigates the molecular basis underlying the benefits of resistance exercise in aging C57BL/6J mice of both sexes.ResultsThis study is the first to demonstrate that long-term (34 weeks) voluntary resistance wheel exercise (RWE) initiated at middle age, from 15 months, prevents sarcopenia in selected hindlimb muscles and causes hypertrophy in soleus, by 23 months of age in both male and female C57BL/6J mice. Compared with 23-month-old sedentary (SED) controls, RWE (0–6 g of resistance) increased intramuscular mitochondrial density and oxidative capacity (measured by citrate synthase and NADH-TR) and increased LC3II/I ratios (a marker of autophagy) in exercised mice of both sexes. RWE also reduced mRNA expression of Gadd45α (males only) and Runx1 (females only) but had no effect on other markers of denervation including Chrng, Chrnd, Musk, and Myog. RWE increased heart mass in all mice, with a more pronounced increase in females. Significant sex differences were also noted among SED mice, with Murf1 mRNA levels increasing in male, but decreasing in old female mice between 15 and 23 months.ConclusionsOverall, long-term RWE initiated from 15 month of age significantly improved some markers of the mitochondrial and autophagosomal pathways and prevented age-related muscle wasting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-016-0117-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 54%

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

et al. 2016

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“…Nonetheless, the tendency for a reduced LC3 II to LC3 I ratio between days 3 and 7 suggests that muscle autophagic flux may become more activated when the CCA-induced mitochondrial adaptations culminate. Likewise, other studies have also claimed that endurance exercise training decreased the LC3 II to LC3 I ratio in the skeletal muscle of humans (Fritzen et al 2016) and rodents (McMillan et al 2015), probably due to the increase in LC3 I protein abundance.…”

Section: Discussionmentioning

confidence: 82%

“…; McMillan et al. ; Tam et al. ) term endurance training do not alter those transcript and/or protein levels in skeletal muscle.…”

Section: Discussionmentioning

confidence: 97%

Regulation of the autophagy system during chronic contractile activity-induced muscle adaptations

Kim

Hood

2017

Physiol Rep

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Skeletal muscle is adaptable to exercise stimuli via the upregulation of mitochondrial biogenesis, and recent studies have suggested that autophagy also plays a role in exercise‐induced muscle adaptations. However, it is still obscure how muscle regulates autophagy over the time course of training adaptations. This study examined the expression of autophagic proteins in skeletal muscle of rats exposed to chronic contractile activity (CCA; 6 h/day, 9V, 10 Hz continuous, 0.1 msec pulse duration) for 1, 3, and 7 days (n = 8/group). CCA‐induced mitochondrial adaptations were observed by day 7, as shown by the increase in mitochondrial proteins (PGC‐1α, COX I, and COX IV), as well as COX activity. Notably, the ratio of LC3 II/LC3 I, an indicator of autophagy, decreased by day 7 largely due to a significant increase in LC3 I. The autophagic induction marker p62 was elevated on day 3 and returned to basal levels by day 7, suggesting a time‐dependent increase in autophagic flux. The lysosomal system was upregulated early, prior to changes in mitochondrial proteins, as represented by increases in lysosomal system markers LAMP1, LAMP2A, and MCOLN1 as early as by day 1, as well as TFEB, a primary regulator of lysosomal biogenesis and autophagy flux. Our findings suggest that, in response to chronic exercise, autophagy is upregulated concomitant with mitochondrial adaptations. Notably, our data reveal the surprising adaptive plasticity of the lysosome in response to chronic contractile activity which enhances muscle health by providing cells with a greater capacity for macromolecular and organelle turnover.

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“…), but some opposing results have also been documented (McMillan et al . ; Mejías‐Peña et al . ; Kim & Hood, ).…”

Section: Discussionmentioning

confidence: 99%

Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity

Carter

Kim

Erlich

et al. 2018

The Journal of Physiology

113

111

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Skeletal muscle exhibits deficits in mitochondrial quality with age. Central to the maintenance of a healthy mitochondrial pool is the removal of dysfunctional organelles via mitophagy. Little is known on how mitophagy is altered with ageing and chronic exercise. We assessed mitophagy flux using colchicine treatment in vivo following chronic contractile activity (CCA) of muscle in young and aged rats. CCA evoked mitochondrial biogenesis in young muscle, with an attenuated response in aged muscle. Mitophagy flux was higher in aged muscle and was correlated with the enhanced expression of mitophagy receptors and upstream transcriptional regulators. CCA decreased mitophagy flux in both age groups, suggesting an improvement in organelle quality. CCA also reduced the exaggerated expression of TFEB evident in aged muscle, which may be promoting the age-induced increase in lysosomal markers. Thus, aged muscle possesses an elevated drive for autophagy and mitophagy which may contribute to the decline in organelle content observed with age, but which may serve to maintain mitochondrial quality. CCA improves organelle integrity and reduces mitophagy, illustrating that chronic exercise is a modality to improve muscle quality in aged populations.

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Autophagic Signaling and Proteolytic Enzyme Activity in Cardiac and Skeletal Muscle of Spontaneously Hypertensive Rats following Chronic Aerobic Exercise

Cited by 41 publications

References 66 publications

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

Regulation of the autophagy system during chronic contractile activity-induced muscle adaptations

Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity

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