Autophagy as a Therapeutic Target to Enhance Aged Muscle Regeneration

Lee, David E.; Bareja, Akshay; Bartlett, David B.; White, James P.

doi:10.3390/cells8020183

Cited by 53 publications

(49 citation statements)

References 161 publications

(205 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since some studies have found that autophagy is activated, V-ATPase expression and lysosomal acidication are upregulated during tissue regeneration, 6,7,[80][81][82][83] and the observed phenomenon of lysosomal acidication in our work is consistent with the reported results. But our research provides…”

Section: Quantication Of Lysosomal Ph In Vitrosupporting

confidence: 93%

In vivomonitoring of tissue regeneration using a ratiometric lysosomal AIE probe

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Quantication Of Lysosomal Ph In Vitrosupporting

confidence: 93%

In vivomonitoring of tissue regeneration using a ratiometric lysosomal AIE probe

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Skeletal muscle regenerative capacity declines with aging owing to a suppression of autophagy in multiple cell types (Lee et al, 2019). Hence, we envisioned that ARHGEF3 KO with autophagy-promoting effect would counteract the age-related decline in muscle regenerative capacity.…”

Section: Arhgef3 Ko Promotes Muscle Regeneration Through Autophagy Anmentioning

confidence: 99%

ARHGEF3 regulates skeletal muscle regeneration and strength through autophagy

You

Singh

Reyes-Ordoñez

et al. 2020

Preprint

View full text Add to dashboard Cite

Skeletal muscle regeneration is essential for restoring muscle function upon injury and for the maintenance of muscle health with aging. ARHGEF3, a Rho-specific GEF, negatively regulates myoblast differentiation via mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling in a GEF-independent manner in vitro. Here, we investigated ARHGEF3's role in skeletal muscle regeneration by creating ARHGEF3 KO mice. These mice exhibited no discernible phenotype under normal conditions. Upon injury, however, ARHGEF3 deficiency enhanced the mass, fiber size and function of regenerating muscles in both young and aged mice. Surprisingly, these effects were not mediated by mTORC2-Akt signaling, but by the GEF activity of ARHGEF3. Furthermore, ARHGEF3 KO promoted muscle regeneration through activation of autophagy, a process that is also critical for maintaining muscle strength.Accordingly, in old mice, ARHGEF3 depletion prevented muscle weakness by restoring autophagy flux. Collectively, our findings identify an unexpected link between ARHGEF3 and autophagy-related muscle pathophysiology.

show abstract

“…Increasing evidence shows that autophagy defective is implicated in aging and age-related pathologies. Thus, pharmacologically stimulated autophagy may ameliorate the symptoms of age-associated phenotypes [33,34]. Mitophagy is a specialized form of autophagy that degraded the damaged and dysfunctional mitochondria [35].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease

Xia

Xie

Ding

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined.Methods: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP + )-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. Results:We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP + -induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. Conclusions: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.

show abstract

Autophagy as a Therapeutic Target to Enhance Aged Muscle Regeneration

Cited by 53 publications

References 161 publications

In vivomonitoring of tissue regeneration using a ratiometric lysosomal AIE probe

In vivomonitoring of tissue regeneration using a ratiometric lysosomal AIE probe

ARHGEF3 regulates skeletal muscle regeneration and strength through autophagy

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease

Contact Info

Product

Resources

About