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.
It is well established that impairments in mitochondrial function/regulation contribute to tissue decline with aging. Caloric restriction (CR) and resveratrol (RSV) treatment in rodents induces beneficial mitochondrial adaptations in tissues such as heart and skeletal muscle but whether similar benefits occur in fat is unknown. Thus, we investigated whether RSV (50 mg/kg/day; 6 weeks) and/or CR (20% reduced AL; 6 weeks) could alter mitochondrial regulation/biogenesis in aged rodent adipose tissues (visceral; VIS, epididymal; EPI, brown adipose tissue; BAT). Aged F344xBN rats (26 mo) were divided into 4 groups (n=4): ad libitum (AL), CR, RSV, RSV+CR and mitochondrial content (cyto c, COX activity, and COX I) and mitochondrial signaling/regulation (AMPK, PGC‐1α) were assessed. Expectedly, mitochondrial content (cyto c, COX activity) and PGC‐1α were significantly elevated (~2–3‐fold) in the BAT compared to EPI and VIS fat. CR and RSV tended to increase COX activity (~20–50%) in all adipose depots but showed inconsistencies with other mitochondrial content/signaling markers. Interestingly, combined CR and RSV treatment had no effect and/or suppressed COX activity in all adipose tissues. Our data indicates that short‐term CR and RSV treatment when applied independently appears to enhance mitochondrial content in adipose tissue and may contribute to improvements in health associated with these paradigms.
Sarcopenia is an age‐related loss in muscle mass partially attributable to mitochondrial‐mediated apoptosis. Caloric restriction (CR) and resveratrol (RSV) treatment in rodents induces beneficial mitochondrial alterations which may serve to suppress sarcopenia. Doxorubicin (DOX) is a chemotherapeutic agent that induces cell death via mitochondria. We investigated whether RSV (50 mg/kg/day; 6 weeks) and/or CR (20% reduced AL; 6 weeks) could 1) induce mitochondrial biogenesis, 2) attenuate apoptotic susceptibility and, 3) reduce DOX‐induced toxicity, in aged rodent muscle. Aged F344xBN rats (26 mo) were split into 8 groups (n=4): ad libitum (AL), CR, RSV, RSV+CR and injected with DOX (20 mg/kg; IP) or saline prior (24h) to sacrifice. Mitochondrial content/regulation (cyto c, COX activity, PGC‐1á, SIRT3) and apoptotic susceptibility (Bax:Bcl‐2) were assessed in hindlimb muscle. Surprisingly, mitochondrial indices were unaffected by CR, RSV or CR+RSV, and DOX did not affect any group. CR+RSV reduced (50%) the Bax:Bcl2 ratio compared to AL while RSV and CR independently showed trends for reductions. DOX treatment enhanced the Bax:Bcl‐2 in AL while CR, RSV and CR+RSV tended to suppress this DOX‐induction. Our data indicates aged muscle, and DOX‐treatment, increases apoptotic susceptibility and CR+RSV treatment provides modest protection without altering mitochondrial content/regulation.
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