Abstract
The world’s elderly population is expanding rapidly, and we are now faced with the significant challenge of maintaining or improving physical activity, independence, and quality of life in the elderly. Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and often, frailty. Muscle loss has been linked with several proteolytic systems, including the ubuiquitin-proteasome and lysosome-autophagy systems. Although many factors are considered to regulate age-dependent muscle loss, this gentle atrophy is not affected by factors known to enhance rapid atrophy (denervation, hindlimb suspension, etc.). In addition, defects in Akt-mammalian target of rapamycin (mTOR) and serum response factor (SRF)-dependent signaling have been found in sarcopenic muscle. Intriguingly, more recent studies indicate an apparent functional defect in autophagy-dependent signaling in sarcopenic muscle. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. Treatment with ursolic acid seems to be effective as therapeutic agents for sarcopenia, because they attenuate the degenerative symptoms of cachexic muscle. Pharmacological, hormonal, and supplemental approaches have been tried to attenuate sarcopenia, but did not obtain outstanding results. In this review, we summarize the current understanding of the adaptation of many regulators in sarcopenia and more recent therapeutic strategies (myostatin inhibition, supplementation with ghrelin or ursolic acid, etc.) for counteracting sarcopenia.
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Abbreviations
- ACE:
-
angiotensin-converting enzyme
- ActRIIB:
-
activin receptor IIB
- ALK:
-
activin receptor-like kinase
- Atg:
-
autophagy-related genes
- atrogin-1:
-
atrophy gene-1
- BCAA:
-
branched chain amino acid
- CR:
-
caloric restriction
- DHEA:
-
dehydroepiandrosterone
- DMD:
-
Duchenne muscular dystrophy
- eIF:
-
eukaryotic initiation factor
- 4E-BP:
-
eIF 4E binding protein
- FOXO:
-
forkhead box O
- GH:
-
growth hormone
- GSK:
-
glycogen synthase kinase
- IGF-I:
-
insulin-like growth factor-I
- IL:
-
interleukin
- JAK:
-
Janus kinase
- KO:
-
knockout
- MRTF:
-
myocardin-related transcription factor
- mTOR:
-
mammalian target of rapamycin
- mTORC:
-
mTOR signaling complex
- MuRF:
-
muscle ring-finger protein
- NF-ÎşB:
-
nuclear factor-kappaB
- NMJ:
-
neuromuscular junction
- PGC-1α:
-
peroxisome proliferator-activated receptor γ coactivator 1α
- PI3-K:
-
phosphatidylinositol 3-kinase
- p70S6K:
-
p70 ribosomal protein S6 kinase
- RDA:
-
recommended dietary allowance
- Rheb:
-
Ras homolog enriched in brain
- ROS:
-
reactive oxidative species
- SRF:
-
serum response factor
- STARS:
-
striated muscle activators of Rho signaling
- STAT:
-
signal transducer and activator of transcription
- TNF-α:
-
tumor necrosis factor-α
- TSC:
-
tuberous sclerosis complex
- UPS:
-
ubiquitin-proteasome system
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Acknowledgments
This work was supported by a research Grant-in-Aid for Scientific Research C (No. 26350815) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Sakuma, K., Yamaguchi, A. (2015). Sarcopenia and Its Intervention. In: Yu, B. (eds) Nutrition, Exercise and Epigenetics: Ageing Interventions. Healthy Ageing and Longevity, vol 2. Springer, Cham. https://doi.org/10.1007/978-3-319-14830-4_7
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