Abstract
We hypothesized that treatment with pharmacological agents known to increase sirtuin-1 activity (resveratrol and curcumin) may enhance muscle regeneration. In limb muscles of mice (C57BL/6J, 10 weeks) exposed to reloading for seven days following a seven-day period of hindlimb immobilization with/without curcumin or resveratrol treatment, progenitor muscle cell numbers (FACS), satellite cell subtypes (histology), early and late muscle regeneration markers, phenotype and morphometry, sirtuin-1 activity and content, and muscle function were assessed. Treatment with either resveratrol or curcumin in immobilized muscles elicited a significant improvement in numbers of progenitor, activated, quiescent, and total counts of muscle satellite cells, compared to non-treated animals. Treatment with either resveratrol or curcumin in reloaded muscles compared to non-treated mice induced a significant improvement in the CSA of both hybrid (curcumin) and fast-twitch fibers (resveratrol), sirtuin-1 activity (curcumin), sirtuin-1 content (resveratrol), and counts of progenitor muscle cells (resveratrol). Treatment with the pharmacological agents resveratrol and curcumin enhanced the numbers of satellite cells (muscle progenitor, quiescent, activated, and total satellite cells) in the unloaded limb muscles but not in the reloaded muscles. These findings have potential clinical implications as treatment with these phenolic compounds would predominantly be indicated during disuse muscle atrophy to enhance the muscle regeneration process.
Highlights
Disuse muscle atrophy is an important condition that is the result of progression of other chronic and acute diseases, such as cardiac and respiratory disorders; cancer; prolonged bed rest; and critical illness
The current hypothesis was that treatment with pharmacological agents known to increase sirtuin-1 activity, among other functions, may enhance muscle regeneration as evaluated by the identification of biological players clearly involved in this process in the limb muscles of mice exposed to muscle reloading following a period of hindlimb unloading
In a previous study from our group [30], curcumin elicited an improvement in muscle phenotype and function via attenuation of NF-kB activity in mice exposed to the same experimental conditions as in the present study. These findings suggest that NF-kB is a probably a major regulator of the muscle regeneration process detected in the hindlimb muscles of mice in the present investigation
Summary
Disuse muscle atrophy is an important condition that is the result of progression of other chronic and acute diseases, such as cardiac and respiratory disorders; cancer; prolonged bed rest; and critical illness. Muscle regeneration relies widely on the interaction between satellite cells and the microenvironment Their numbers and subtypes may vary according to the underlying condition, such as during muscle atrophy [11,13,14], exposure to cigarette smoking [15], aging [16], and prolonged bed rest [17]. Sirtuin-1 activity may promote muscle repair and regeneration following disuse muscle atrophy [25] On this basis, the current hypothesis was that treatment with pharmacological agents (resveratrol and curcumin) known to increase sirtuin-1 activity, among other functions, may enhance muscle regeneration as evaluated by the identification of biological players clearly involved in this process in the limb muscles of mice exposed to muscle reloading following a period of hindlimb unloading. Previously been well validated [6,7,8]
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