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l-Lysine suppresses myofibrillar protein degradation and autophagy in skeletal muscles of senescence-accelerated mouse prone 8

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Abstract

Sarcopenia is a condition of the loss of muscle mass that is associated with aging and that increases the risk for bedridden state, thereby warranting studies of interventions that attenuate sarcopenia. Here the effects of 2-month dietary l-lysine (Lys) supplementation (1.5–3.0 %) on myofibrillar protein degradation and major proteolytic systems were investigated in senescence-accelerated mouse prone 8 (SAMP8). At 36 weeks of age, skeletal muscle and lean body mass was reduced in SAMP8 when compared with control senescence-accelerated mouse resistant 1 (SAMR1). The myofibrillar protein degradation, which was evaluated by the release of 3-methylhistidine, was stimulated in SAMP8, and the autophagy activity, which was evaluated by light chain 3-II, was stimulated in the skeletal muscle of SAMP8. The activation of ubiquitin-proteasome system was not observed in the muscles of SAMP8. However, myofibrillar protein degradation and autophagic activity in skeletal muscles of SAMP8 were suppressed by dietary intake of 3.0 % Lys. The present data indicate that myofibrillar protein degradation by bulk autophagy is stimulated in the skeletal muscles of SAMP8 and that dietary Lys supplementation attenuates sarcopenia in SAMP8 by suppressing autophagic proteolysis.

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Abbreviations

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

LC3:

Light chain 3

Lys:

l-Lysine

MeHis:

3-Methylhistidine

mTOR:

Mammalian target of rapamycin

Mul1:

Mitochondrial E3 ubiquitin protein ligase 1

MuRF1:

Muscle ring-finger protein 1

PGC-1α:

Peroxisome proliferator activated receptor γ co-activator 1α

qRT-PCR:

Quantitative reverse transcription PCR

SAMP8:

Senescence-accelerated mouse prone 8

SAMR1:

Senescence-accelerated mouse resistant 1

S6K1:

p70 ribosomal protein S6 kinase 1

UPS:

Ubiquitin-proteasome system

4E-BP1:

Eukaryotic initiation factor 4E binding protein 1

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Acknowledgments

Amino acids were provided by Ajinomoto Co., Inc. Primer sequences for atrogin-1 and MuRF1 were provided by Professor Takeshi Nikawa, Tokushima University, Japan.

Funding

This work was supported by the Sasakawa Scientific Research Grant from The Japan Science Society (Grant No. 27-414).

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Correspondence to Tomonori Sato.

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We declare no conflict of interest related to this study.

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Human subject is not involved in this study.

Research involving Animals

Male SAMP8 (15-week-old, 27–35 g, n = 17) and SAMR1 (15-week-old, 31–35 g, n = 6) were purchased from Japan SLC, Inc. (Shizuoka, Japan). All animal protocols were approved by the Iwate University Animal Research Committee and were performed in compliance with the Guidelines for Animal Experiments of Iwate University (approval number, A201517).

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Sato, T., Ito, Y. & Nagasawa, T. l-Lysine suppresses myofibrillar protein degradation and autophagy in skeletal muscles of senescence-accelerated mouse prone 8. Biogerontology 18, 85–95 (2017). https://doi.org/10.1007/s10522-016-9663-7

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  • DOI: https://doi.org/10.1007/s10522-016-9663-7

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