Leucine supplementation improves regeneration of skeletal muscles from old rats.
The decreased regenerative capacity of old skeletal muscles involves disrupted turnover of proteins. This study investigated whether leucine supplementation in old rats could improve muscle regenerative capacity. Young and old male Wistar rats were supplemented with leucine; then, the muscles were cryolesioned and examined after 3 and 10 days. Leucine supplementation attenuated the decrease in the expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4E (eIF4E) in young and old muscles on day 3 post-injury and promoted an increase in the cross-sectional area of regenerating myofibers from both young and old soleus muscles on day 10 post-injury. This supplementation decreased the levels of ubiquitinated proteins and increased the proteasome activity in young regenerating muscles, but the opposite effect was observed in old regenerating muscles. Moreover, leucine decreased the inflammation area and induced an increase in the number of proliferating satellite cells in both young and old muscles. Our results suggest that leucine supplementation improves the regeneration of skeletal muscles from old rats, through the preservation of certain biological responses upon leucine supplementation. Such responses comprise the decrease in the inflammation area, increase in the number of proliferating satellite cells and size of regenerating myofibers, combined with the modulation of components of the phosphoinositide 3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and ubiquitin-proteasome system.
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Prof. Lineu Prestes Av. 2415, São Paulo, SP 05508-000, Brazil. Electronic address: pereiramg@gmail.com.
Marcelo G
MG
Pereira
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Prof. Lineu Prestes Av. 2415, São Paulo, SP 05508-000, Brazil. Electronic address: me_tomaz@hotmail.com.
Meiricris T
MT
Silva
Department of Biochemistry, Federal University of São Paulo, 3 de Maio St. 100, São Paulo, SP, Vila Clementino, 04044-020, Brazil. Electronic address: fmcunha@unifesp.br.
Fernanda M
FM
da Cunha
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Prof. Lineu Prestes Av. 2415, São Paulo, SP 05508-000, Brazil. Electronic address: moriscot@usp.br.
Anselmo S
AS
Moriscot
School of Arts, Sciences and Humanities, University of São Paulo, Arlindo Bettio Av. 1000, São Paulo, SP 03828-000, Brazil. Electronic address: aoki.ms@usp.br.
Marcelo S
MS
Aoki
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Prof. Lineu Prestes Av. 2415, São Paulo, SP 05508-000, Brazil. Electronic address: elenm@usp.br.
Elen H
EH
Miyabara
D000375:Aging / Q000187:drug effects*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D019587:Dietary Supplements; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism
D002352:Carrier Proteins; D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D057149:Ubiquitinated Proteins; C499526:Eif4ebp1 protein, rat; C546845:mTOR protein, rat; C111490:Akt3 protein, rat
Aging; Leucine supplementation; Regeneration; Skeletal muscle