Caloric Restriction Mimetics Slow Aging of Neuromuscular Synapses and Muscle Fibers.
Resveratrol and metformin have been shown to mimic some aspects of caloric restriction and exercise. However, it remains unknown if these molecules also slow age-related synaptic degeneration, as previously shown for caloric restriction and exercise. In this study, we examined the structural integrity of neuromuscular junctions (NMJs) in 2-year-old mice treated with resveratrol and metformin starting at 1 year of age. We found that resveratrol significantly slows aging of NMJs in the extensor digitorum longus muscle of 2-year-old mice. Resveratrol also preserved the morphology of muscle fibers in old mice. Although metformin slowed the rate of muscle fiber aging, it did not significantly affect aging of NMJs. Based on these findings, we sought to determine if resveratrol directly affects NMJs. For this, we examined postsynaptic sites, the NMJ region located on the muscle peripheral membrane, on cultured myotubes derived from C2C12 cells. We discovered that resveratrol increases the number of postsynaptic sites on myotubes exhibiting a youthful architecture, suggesting that resveratrol directly affects the NMJ. Altogether, we provide compelling evidence indicating that resveratrol slows aging of NMJs and muscle fibers.
Virginia Tech Carilion Research Institute, Roanoke College, Virginia.|Department of Biology, Roanoke College, Virginia.
Jessica
J
Stockinger
Virginia Tech Carilion Research Institute, Roanoke College, Virginia.
Nicholas
N
Maxwell
Virginia Tech Carilion Research Institute, Roanoke College, Virginia.
Dillon
D
Shapiro
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland.
Rafael
R
deCabo
Virginia Tech Carilion Research Institute, Roanoke College, Virginia.|Department of Biological Sciences, Virginia Tech.
Gregorio
G
Valdez
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D031204:Caloric Restriction / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004734:Energy Metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D000068079:Motor Disorders / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000975:Antioxidants; D007004:Hypoglycemic Agents; D013267:Stilbenes; D008687:Metformin; D000077185:Resveratrol
Metabolism; Metformin; Myotube; NMJ; Resveratrol