stilbenes and Sarcopenia

Topics: Aging; Animals; Hypertrophy; Mice; Muscle, Skeletal; Myocytes, Cardiac; Resveratrol; Sarcopenia; Sirtuin 1; Stilbenes

Sarcopenia is an age-related syndrome characterized by progressive loss of muscle mass and function. Exercise is an important strategy to prolong life and increase muscle mass, and resveratrol has been shown a variety beneficial effects on skeletal muscle. In the present study, we investigated the potential efficacy of using short-term exercise (six weeks), resveratrol (150mg/kg/day), or combined exercise+resveratrol (150mg/kg/day) on gastrocnemius muscle mass, grip strength, cross-sectional area and microscopic morphology in aged rats, and explored the potential mechanism at the apoptosis level. Six months old SD rats were used as young control group and 24months old SD rats were adopted as aged group. After six weeks intervention, the data provide evidence that exercise, resveratrol or their combination significantly increase the relative grip strength and muscle mass in aged rats (P<0.05). Electron microscopy discovered a significant increase in sarcomere length, I-band and H-zone in aged rats (P<0.05), and exercise, resveratrol or their combination significantly reduced the increasement (P<0.05). Moreover, light microscopy revealed a significant increase on Feret's diameter and cross-sectional area (CSA) in aged rats (P<0.05), but exercise and resveratrol did not show significant effects on them (P>0.05). Furthermore, exercise, resveratrol or their combination significantly increased the expression of p-AMPK and SIRT1, decreased the expression of acetyl P53 and Bax/Bcl-2 ratio in aged rats (P<0.05). These findings show that aged rats show significant changes in gastrocnemius muscle morphology and ultrastructure, and the protective effects of exercise, resveratrol and their combination are probably associated with anti-apoptotic signaling pathways through activation of AMPK/Sirt1.

Topics: Age Factors; Aging; AMP-Activated Protein Kinases; Animals; Apoptosis; bcl-2-Associated X Protein; Combined Modality Therapy; Disease Models, Animal; Exercise Therapy; Male; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Physical Conditioning, Animal; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Resveratrol; Sarcopenia; Signal Transduction; Sirtuin 1; Stilbenes; Time Factors; Tumor Suppressor Protein p53

Aging is associated with a loss in muscle known as sarcopenia that is partially attributed to apoptosis. In aging rodents, caloric restriction (CR) increases health and longevity by improving mitochondrial function and the polyphenol resveratrol (RSV) has been reported to have similar benefits. In the present study, we investigated the potential efficacy of using short-term (6 weeks) CR (20%), RSV (50 mg/kg/day), or combined CR+ RSV (20% CR and 50 mg/kg/day RSV), initiated at late-life (27 months) to protect muscle against sarcopenia by altering mitochondrial function, biogenesis, content, and apoptotic signaling in both glycolytic white and oxidative red gastrocnemius muscle (WG and RG, respectively) of male Fischer 344 × Brown Norway rats. CR but not RSV attenuated the age-associated loss of muscle mass in both mixed gastrocnemius and soleus muscle, while combined treatment (CR + RSV) paradigms showed a protective effect in the soleus and plantaris muscle (P < 0.05). Sirt1 protein content was increased by 2.6-fold (P < 0.05) in WG but not RG muscle with RSV treatment, while CR or CR + RSV had no effect. PGC-1α levels were higher (2-fold) in the WG from CR-treated animals (P < 0.05) when compared to ad-libitum (AL) animals but no differences were observed in the RG with any treatment. Levels of the anti-apoptotic protein Bcl-2 were significantly higher (1.6-fold) in the WG muscle of RSV and CR + RSV groups compared to AL (P < 0.05) but tended to occur coincident with elevations in the pro-apoptotic protein Bax so that the apoptotic susceptibility as indicated by the Bax to Bcl-2 ratio was unchanged. There were no alterations in DNA fragmentation with any treatment in muscle from older animals. Additionally, mitochondrial respiration measured in permeabilized muscle fibers was unchanged in any treatment group and this paralleled the lack of change in cytochrome c oxidase (COX) activity. These data suggest that short-term moderate CR, RSV, or CR + RSV tended to modestly alter key mitochondrial regulatory and apoptotic signaling pathways in glycolytic muscle and this might contribute to the moderate protective effects against aging-induced muscle loss observed in this study.

Topics: Aging; AMP-Activated Protein Kinases; Animals; Apoptosis; Apoptosis Regulatory Proteins; Caloric Restriction; Combined Modality Therapy; Male; Mitochondria, Muscle; Mitochondrial Proteins; Muscle, Skeletal; Organ Size; Oxygen Consumption; Rats; Rats, Inbred F344; Resveratrol; Sarcopenia; Sirtuin 1; Stilbenes

This study analyzed the capacity of resveratrol, a naturally occurring polyphenol, to reduce aging-induced oxidative stress and protect against sarcopenia. Middle-aged (18 months) C57/BL6 mice were randomly assigned to receive either a control diet or a diet supplemented with 0.05% trans-resveratrol for 10 months. Young (6 months) and middle-aged (18 months) mice were used as controls. Resveratrol supplementation did not reduce the aging-associated loss of muscle mass or improve maximal isometric force production, but it appeared to preserve fast-twitch fiber contractile function. Resveratrol supplementation did not improve mitochondrial content, the subcellular localization of cytochrome c protein content, or PGC1 protein content. Resveratrol increased manganese superoxide dismutase (MnSOD), reduced hydrogen peroxide(,) and lipid peroxidation levels in muscle samples, but it was unable to significantly reduce protein carbonyl levels. The data suggest that resveratrol has a protective effect against aging-induced oxidative stress in skeletal muscle, likely through the upregulation of MnSOD activity, but sarcopenia was not attenuated by resveratrol.

Topics: Aging; Animals; Antioxidants; Dietary Supplements; Disease Models, Animal; Follow-Up Studies; Immunoblotting; Isometric Contraction; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Muscle, Skeletal; Oxidative Stress; Resveratrol; Ribonucleotide Reductases; Sarcopenia; Stilbenes; Time Factors