Satellite Cells and Markers of Muscle Regeneration during Unloading and Reloading: Effects of Treatment with Resveratrol and Curcumin

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.

Curcumin and Resveratrol Improve Muscle Function and Structure through Attenuation of Proteolytic Markers in Experimental Cancer-Induced Cachexia

“…Interestingly, the inhibition of NF-κB activity elicited by curcumin was shown to improve the phenotype and function of skeletal muscles in several models characterized by alterations of this tissue [ 11 , 12 , 13 ]. Furthermore, treatment of mice with the NF-κB inhibitor curcumin also favored the process of muscle regeneration in experimental models of disuse muscle atrophy [ 14 , 15 ]. In a subacute model of oncologic cachexia in rats, however, curcumin significantly reduced tumor growth, while it was not able to attenuate muscle protein loss [ 16 ].…”

“…Muscle injury also diminished in the gastrocnemius of the rats that received treatment with resveratrol [ 24 ]. In mice exposed to hindlimb immobilization, muscle recovery and regeneration following atrophy were also significantly favored by the action of resveratrol treatment [ 15 ]. In subacute in vivo models of cancer cachexia, however, resveratrol did not elicit an improvement in muscle wasting [ 25 ].…”

Mitochondrial Bioenergetics and Turnover during Chronic Muscle Disuse

“…With denervation, PGC-1α mRNA and protein content are reduced within as short a period as one day and can remain depressed over many weeks [ 90 , 94 , 95 ]. Similarly, hindlimb unloading or immobilization can produce marked decrements in PGC-1α mRNA and protein content [ 91 , 96 ]. Moreover, reductions in Tfam gene expression have been observed in unloaded tissue, while downregulations in the gene and protein expression of reliable mitochondrial markers, including those involved in oxidative phosphorylation, have been observed across many models of disuse [ 52 , 73 , 89 , 90 , 92 , 97 , 98 , 99 ].…”

PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging

“…In aged rats, resveratrol treatment improved muscle mass and myofiber CSA during 14 days of recovery following 14 days hindlimb unloading [ 77 ]. In young female mice, following 7 days of unilateral limb immobilization, resveratrol prevented the loss in muscle mass, myofiber CSA and strength while concomitantly increased satellite cell content during 7 day recovery [ 78 ]. In another study in which young adult rats were given resveratrol 4 weeks prior to and during 14 days hindlimb unloading was effective to maintain body and muscle mass, strength, and prevent a glycolytic fiber shift and a decrease in SIRT1 and PGC-1α protein expression [ 79 ].…”

“…The effectiveness of resveratrol on muscle function during disuse and recovery may be related to reduced fibrosis, increased ROS scavenging, preserved lipid substrate utilization and mitochondrial function, and augmented satellite cell abundance [ 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. A common result of resveratrol treatment, irrespective of dose, administration route, and timing, is a muscle oxidative fiber type shift due to an upregulation of SIRT1 and PGC-1α expression [ 77 , 78 , 79 , 83 , 84 , 85 ]. The dependency of SIRT1 is noted by a reduced ability to prevent dexamethasone-induced L6 myotube atrophy in the presence of resveratrol when SIRT1 is blocked [ 86 ].…”