Curcumin Supplementation and Aging Skeletal Muscle
Date of Award
Doctor of Philosophy (PhD)
Keith C. DeRuisseau
curcumin, muscle, oxidative stress, sarcopenia
Medicine and Health Sciences
Sarcopenia, which is the decline in muscle mass and function with advancing age, can decrease quality of life and lead to an inability to perform activities of daily living. One of the contributors to the development of sarcopenia is a rise in skeletal muscle oxidative stress. This increase may be the result of several factors that include elevated non-heme iron (NHI) concentration and a compromised antioxidant defense system. Curcumin, which is the active ingredient in the spice turmeric, may serve as a possible intervention for sarcopenia. Previous work has utilized curcumin as a therapeutic agent for cancer patients because of its antioxidant properties. However, no studies to date have explored the potential role of curcumin in attenuating the development of sarcopenia. It was reported that curcumin can act as an iron chelator and trigger the activation of nuclear factor erythroid-2-related-factor-2 (Nrf2); a transcription factor important to antioxidant upregulation. Through these mechanisms, it is possible that curcumin can attenuate the rise in oxidative stress in aging muscle. Hence, the goal of this study was to characterize the role of curcumin in altering the redox status of skeletal muscle, along with subsequent changes to muscle mass and function.
Thirty-two-month-old and eight-month-old male F344xBN rats were studied and fed a control diet (AIN-93M) with or without the addition of 0.2% curcumin (food weight) over a period of 4 months. A pair fed group was also included to account for any reduction in food consumption among curcumin supplemented animals due to palatability issues. The thirty-two-month-old animals served as a model for aging, as animals of this age have already begun to see a decline in muscle mass and function. The eight-month old animals are indicative of a ‘young-adult’ group, as F344xBN animals are continuing to grow at this point; hence, differences within this age group could be telling of curcumin’s potential benefits to healthy muscle. The following groups were examined to establish the role of curcumin on skeletal muscle: 36-month-old control (36CON; n=18); 36-month-old consuming 0.2% curcumin (36CUR; n=18); 36-month-old pair fed (36PAIR; n=18); 12-month-old control (12CON; n=11); 12-month-old consuming 0.2% curcumin (12CUR; n=11); and 12-month-old pair fed (12PAIR; n=11). Following the experimental period, animals underwent a muscle contractile protocol and were euthanized to determine whether long term dietary exposure to curcumin can alter: 1) skeletal muscle antioxidant measures and Nrf2 activation; 2) skeletal muscle iron status and oxidative stress; and 3) skeletal muscle force generation and muscle mass.
There was a lower food consumption among the 36CUR animals compared to the 36CON rats, and thus a difference between the 36CON and 36PAIR groups (p < 0.05). The 36CUR rats displayed a significantly larger plantaris mass compared to the 36PAIR animals (p < 0.05). Similarly, 36CUR rats showed larger twitch and tetanic force generation when compared to the 36PAIR rats (p < 0.05). As expected, there were no differences in dietary intake between the 12-month-old groups. The dietary intervention resulted in significant differences in muscle mass between the 12CUR and 12CON groups in addition to differences in specific twitch tension (p < 0.05). The 12CUR rats displayed significantly greater muscle mass and twitch values compared to 12CON rats. Biochemical analyses uncovered varying responses between feeding groups that differed among age groups. There were no significant differences in measures of antioxidant or iron status measures among the aged rats. Nrf2 nuclear levels (p < 0.01), and measures of oxidative damage including 3-nitrotyrosine (3NT), and protein carbonyls (PC) (p < 0.05) were significantly different between the 36PAIR and 36CUR groups. Interestingly, there were no significant differences between the 36CON and 36CUR groups for any of the measured variables. Similarly, as expected, dietary curcumin did not elicit measurable biochemical changes in the muscle of young adult rats (p > 0.05).
This study suggests that curcumin supplementation exerts positive effects on aged muscle mass and force generation when animals are subjected to food restriction. This was also accompanied with changes to oxidative damage and upregulation of Nrf2 activation. The alterations in muscle mass and twitch force uncovered among the young adult animals suggests there may also be benefit from supplementation at this age. However, these differences were unlikely to be the result of changes in antioxidant capacity or oxidative stress. Future studies should focus on better understanding the other mechanisms by which curcumin may be beneficial to sarcopenic muscle.
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Receno, Candace, "Curcumin Supplementation and Aging Skeletal Muscle" (2017). Dissertations - ALL. 818.