Hyperactive mTORC1 signaling is unaffected by metformin treatment in aged skeletal muscle.
BACKGROUND
Appropriate activation of growth signaling pathways, specifically mammalian target of rapamycin complex 1 (mTORC1), is central to muscle mass and metabolism. The goal of these studies was to examine the effects of metformin on mTORC1 signaling in aged skeletal muscle in an attempt to normalize growth signaling.


METHODS
Aged (23m) and young (3m) male mice were fed a low fat diet without or with 0.5% metformin for up to 8 weeks, then mTORC1-related signaling was examined in the plantar flexor complex.


RESULTS
Metformin had no significant effect on lowering body weight or muscle mass in aged animals, nor altered p70 S6 Kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation. However, it significantly (P < 0.05) reduced body weight and lowered S6K1 and rpS6 phosphorylation in the young.


CONCLUSIONS
Collectively, these data suggest metformin is ineffective at normalizing growth signaling in aged skeletal muscle.
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York, USA.
Cory M
CM
Dungan
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York, USA.
Zhuyun
Z
Li
Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada.
David C
DC
Wright
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York, USA.
David L
DL
Williamson
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000187:drug effects*; D000818:Animals; D005080:Exercise Test; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
C469992:Ddit4 protein, mouse; D015395:Histocompatibility Antigens Class I; D007004:Hypoglycemic Agents; D046912:Multiprotein Complexes; D014157:Transcription Factors; D008687:Metformin; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
AMPK; REDD1; S6K1; aging; rpS6; sarcopenia