Osteoarthritis and sarcopenia are two major joint and skeletal muscle diseases prevalent during aging. Osteoarthritis is a multifactorial progressive degenerative and inflammatory disorder of articular cartilage. Cartilage protection and pain management are the two most important strategies in the management of osteoarthritis. Sarcopenia, a condition of loss of muscle mass and strength, is associated with impaired neuromuscular innervation, the transition of skeletal muscle fiber type, and reduced muscle regenerative capacity. Management of sarcopenia requires addressing both skeletal muscle quantity and quality. Emerging evidence suggests that green tea catechins play an important role in maintaining healthy joints and skeletal muscle. This review covers (i) the prevalence and etiology of osteoarthritis and sarcopenia, such as excessive inflammation and oxidative stress, mitochondrial dysfunction, and reduced autophagy; (ii) the effects of green tea catechins on joint health by downregulating inflammatory signaling mediators, upregulating anabolic mediators, and modulating miRNAs expression, resulting in reduced chondrocyte death, collagen degradation, and cartilage protection; (iii) the effects of green tea catechins on skeletal muscle health via maintaining a dynamic balance between protein synthesis and degradation and boosting the synthesis of mitochondrial energy metabolism, resulting in favorable muscle homeostasis and mitigation of muscle atrophy with aging; and (iv) the current study limitations and future research directions.

Skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and degradation. Several intracellular signaling pathways control this balance, including mammalian/mechanistic target of rapamycin (mTOR) complex 1 (C1). Activation of this pathway in skeletal muscle is controlled, in part, by nutrition (e.g., amino acids and alcohol) and exercise (e.g., resistance exercise (RE)). Acute and chronic alcohol use can result in myopathy, and evidence points to altered mTORC1 signaling as a contributing factor. Moreover, individuals who regularly perform RE or vigorous aerobic exercise are more likely to use alcohol frequently and in larger quantities. Therefore, alcohol may antagonize beneficial exercise-induced increases in mTORC1 pathway signaling. The purpose of this review is to synthesize up-to-date evidence regarding mTORC1 pathway signaling and the independent and combined effects of acute alcohol and RE on activation of the mTORC1 pathway. Overall, acute alcohol impairs and RE activates mTORC1 pathway signaling; however, effects vary by model, sex, feeding, training status, quantity, etc., such that anabolic stimuli may partially rescue the alcohol-mediated pathway inhibition. Likewise, the impact of alcohol on RE-induced mTORC1 pathway signaling appears dependent on several factors including nutrition and sex, although many questions remain unanswered. Accordingly, we identify gaps in the literature that remain to be elucidated to fully understand the independent and combined impacts of alcohol and RE on mTORC1 pathway signaling.

Introduction: The purpose of this study was to determine the effect of resistance exercise (RE)–induced hormonal changes on intramuscular cytokine gene expression after muscle damage in untrained men and women. Methods: Men (n = 8, 22 ± 3 yr) and women (n = 8, 19 ± 1 yr) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either an upper body RE bout (EX) or a time-matched period (CON). Muscle samples (vastus laterals) were analyzed for mRNA expression of interleukin (IL) 6, IL-10, IL-15, TNFA, TGFB, CCL2, and CD68 at PRE, 12 h, and 24 h after the session. Results: A significant time–sex–condition interaction was found for TGFB with an increase for EX in men at 12 h from PRE. For EX, TGFB was also greater in men than in women at 12 and 24 h. Significant time–sex and condition–sex interactions were found for IL-10 with an increase for men that was greater than for women at 12 and 24 h. IL-10 was lower in EX than CON for men. A significant time–sex interaction was found for TNFA with an increase for men that was greater than for women at 24 h. A significant time–condition interaction was found for CD68 with an increase at 12 h and decrease at 24 h for EX and CON. CD68 was lower in EX than CON at 12 h. A significant time effect was found for IL6 and CCL2 with an increase at 12 and 24 h. Conclusions: Results suggest that women seem to have a muted intramuscular cytokine (i.e., IL-10, TNF-α, and TGF-β) response to muscle damage compared with men.

Background/Aim: With diabetes, skeletal muscle mitochondrial quality (fusion, fission & mitophagy) and muscle mass are compromised. Geranylgeraniol (GGOH) can prevent mitochondrial damage, inflammation, and improve muscle health; however, the effect of GGOH on a diabetic model is not known. This study aimed to determine the effect of GGOH on mitochondrial quality and muscle mass in diabetic rats. Materials and Methods: Sprague-Dawley rats were divided into three groups: regular diet (CON; n=7), high-fat-diet with 35 mg/kg body weight of streptozotocin (STZ) (HFD; n=7), and HFD/STZ with 800 mg/kg of GGOH (GG; n=7) for a total of 8 weeks. At the end of the study, soleus and gastrocnemius muscles were collected and analyzed for gene and protein expression of OPA1, MFN2, DRP1, p-DRP, LC3AB, PINK1, Parkin, SOD2, NF- B, IL-6, TNF-α, and IL-1β. Additionally, the cross-sectional area (CSA) of soleus muscles was analyzed. Results: In soleus, HFD group had significantly higher IL-1β and lower LC3A, MFN2, DRP1, and SOD2 mRNA expression compared to CON group. The GG group had higher PINK1 mRNA expression than the HFD group. Additionally, the GG group had lower LC3B and DRP1 protein than the HFD group and lower LC3A and MFN2 protein than the HFD and CON groups. Lastly, HFD and GG groups had a smaller CSA than CON group, whereas GG had a greater CSA than HFD. Conclusion: GGOH supplementation could prevent mitochondrial fragmentation and potentially decrease the demand for mitochondrial fusion. Additionally, autophagosome degradation occurred at a greater rate than formation, indicating increased clearance of damaged organelles. Improved mitochondrial quality could potentially rescue muscle CSA in diabetic rats with GGOH supplementation.

Muscle damage imposes stress on mitochondria resulting in mitochondrial fusion, fission, and mitophagy. Testosterone is a regulator of these processes. However, no study has examined the effect of sex‐specific resistance exercise (RE)‐induced hormonal response on mitochondrial dynamics and mitophagy after muscle damage in untrained men and women. Untrained men and women performed two sessions of 80 unilateral maximal eccentric knee extensions (ECC) followed by upper‐body RE (ECC+RE) aimed to induce hormonal changes and maintain a similar lower body demands between conditions or 20 min seated rest (ECC+REST). Vastus lateralis samples were analyzed for gene and protein expression of OPA1, MFN1, DRP1, PINK1, and Parkin at baseline (BL), 12 and 24 h. Testosterone area under the curve was greater for ECC+RE than ECC+REST in men and was greater in men than women for both conditions. A significant time × sex × condition effect was found for Parkin protein expression. At 12 and 24 h, Parkin was lower for ECC + REST than ECC + RE for men; whereas, Parkin was increased at 24 h for women regardless of condition. A significant time effect was found for OPA1 protein expression increasing at 12 and 24 h. A significant time × sex × condition effects were found for MFN1, DRP1, and PINK1 gene expression with increases at 12 h in men for ECC + RE. A significant time × sex effect was found for OPA1 gene expression with a decrease at 12 h in men, and 12 h expression in men was lower than women. RE‐induced hormonal changes promoted expression of fission, fusion, and mitophagy markers in men. With muscle damage, regardless of condition, expression of inner mitochondrial membrane fusion markers are promoted in both sexes; whereas, those for mitophagy were promoted in women but reduced in men.

Following muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentric exercise-induced muscle damage (EE) between untrained young men and women. Untrained men (n = 8, 22 ± 3 years) and women (n = 8, 19 ± 1 year) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either upper body resistance exercise (RE; designed to induce a hormonal response; EE + RE) or a time-matched rest period (20 min; EE + REST). Vastus lateralis biopsy samples were collected before (BL), and 12 h, and 24 h after RE/REST. Gene and protein expression levels of selective markers for autophagic initiation signaling, phagophore initiation, and elongation/sequestration were determined. Basal markers of autophagy were not different between sexes. For EE + RE, although initiation signaling (FOXO3) and autophagy-promoting (BECN1) genes were greater (p < 0.0001; 12.4-fold, p = 0.0010; 10.5-fold, respectively) for women than men, autophagic flux (LC3-II/LC3-I protein ratio) did not change for women and was lower (p < 0.0001 3.0-fold) than men. Furthermore, regardless of hormonal changes, LC3-I and LC3-II protein content decreased (p = 0.0090; 0.547-fold, p = 0.0410; 0.307-fold, respectively) for men suggesting increased LC3-I lipidation and autophagosome degradation whereas LC3-I protein content increased (p = 0.0360; 1.485-fold) for women suggesting decreased LC3-I lipidation. Collectively, our findings demonstrated basal autophagy was not different between men and women, did not change after EE alone, and was promoted with the acute hormonal increase after RE only in men but not in women. Thus, the autophagy response to moderate muscle damage is promoted by RE-induced hormonal changes in men only.