Yuji Kanazawa

Aging is associated with changes in intramuscular collagen structure and metabolism, which may impair mechanical adaptability and regenerative capacity. We investigated the effects of aging and repeated passive stretching on intramuscular collagen remodeling in the tibialis anterior muscles of mice. The tibialis anterior muscles of young and aged mice were exposed to repeated passive stretching, and the localization of collagen and collagen-related factors was evaluated. Baseline gene expression of collagens I and IV was significantly reduced in aged muscles and was not restored by stretching. Repeated passive stretching increased the area and intensity of collagen I immunoreactivity in both young and aged mice but produced little change in collagen IV. Stretch-induced dynamic changes in lysyl oxidase-positive cells in the extracellular matrix (ECM) were evident in young mice but were markedly attenuated in aged mice. In addition, matrix metalloproteinases (MMP2 and MMP9) mRNA and protein expressions did not differ between groups. No significant age- or stretch-dependent changes were observed in the localization of advanced glycation end products. These findings suggest that although the increase in fibrillar collagen in response to stretching is maintained with aging, the regulatory mechanisms controlling ECM stabilization, particularly those related to cross-linking dynamics, may be impaired.

Background and objective Aging and consumption of a high-fat diet (HFD) are associated with increased body weight and reduced skeletal muscle quality. Although aerobic exercise is generally considered protective against these risks, the impact of self-initiated physical activity on an HFD in older individuals remains unclear. This study aimed to investigate the influence of spontaneous wheel-running on body weight, intramuscular fat accumulation, and mitochondrial metabolic function in the skeletal muscles of young and aged mice on HFD. Methods Male C57BL/6J mice aged 14 weeks (young group) and 84 weeks (aged group) were assigned to either exercise or sedentary groups and fed an HFD for eight weeks. Measurements included body weight, muscle weight (gastrocnemius and soleus), muscle fiber cross-sectional area (FCSA), succinate dehydrogenase (SDH) activity, and intramuscular fat area via Oil Red O staining. Results Voluntary exercise significantly reduced the body weight in both age groups. While the muscle weight and FCSA remained unchanged by exercise, exercise led to elevated SDH activity in the gastrocnemius muscles of both young and aged mice, suggesting increased mitochondrial metabolic activity. Exercise increased intramuscular fat content in the gastrocnemius muscle of young mice, but not in aged mice. The soleus muscle showed a minimal response to both metabolic activity and fat accumulation by exercise, regardless of age. Conclusions Voluntary wheel running under HFD conditions effectively lowered body weight and increased mitochondrial activity in gastrocnemius muscle fibers. However, intramuscular fat responses vary according to muscle type and age, suggesting that aging diminishes skeletal muscle adaptability to exercise in the context of lipid metabolism.

Collagen I is the most abundant type of intramuscular collagen. Lysyl oxidase promotes collagen cross-link formation, which helps stabilize the extracellular matrix. Furthermore, matrix metalloproteinases, responsible for collagen degradation, maintain typical muscle structure and function through remodeling. Although it is well known that aging leads to delayed recovery of muscle fibers, the impact of aging on the remodeling of intramuscular collagen is not well understood. In this study, we investigated the impact of aging on collagen remodeling during muscle injury recovery using young and old mouse models. Muscle injury was induced in the right tibialis anterior (TA) muscle of male C57BL/6J mice [aged 21 weeks (young) and 92 weeks (old)] using intramuscular cardiotoxin injection, with the left TA serving as a sham with saline injection. Following a one-week recovery period, aging was found to delay the recovery of the fiber cross-sectional area. The intensity and area of immunoreactivity for collagen I were significantly increased in old mice compared to young mice post-injury. Additionally, Lox expression and the number of LOX (+) cells in the extracellular matrix significantly increased in old mice compared to young mice post-injury. Furthermore, Mmp9 and MMP9 expression levels after muscle injury were higher in old mice than in young mice. These results suggest that muscle injury in old mice can lead to increased collagen I accumulation, enhanced collagen cross-link formation, and elevated MMP9 expression compared to young mice.

Background/Objectives: Chronic low back pain (CLBP) after middle age is a complex multifactorial condition, and subgrouping is recommended to determine effective treatment strategies. Multidimensional data help create new groupings to increase the effectiveness of interventions in middle-aged and older adults with CLBP. This study aimed to investigate the relationship between the factors associated with CLBP after middle age and to create and characterize a new subgroup based on these factors. Methods: A cross-sectional observational study was conducted and included 46 women aged ≥40 years with CLBP who participated in health events. Trunk muscle mass, lumbar movement control ability, autonomic balance, lumbar tenderness threshold, lumbar proprioception, and severity of central sensitization were assessed. Results: Partial correlation analysis revealed a significant negative correlation between lumbar movement control ability and autonomic balance. A significant positive correlation was observed between trunk muscle mass and the lumbar tenderness threshold. Hierarchical clustering analysis identified three subgroups. The cluster 1 participants had low trunk muscle mass, low tenderness threshold, and low severity of central sensitization. The cluster 2 participants had low trunk muscle mass and tenderness threshold and high severity of central sensitization. The cluster 3 participants had high trunk muscle mass and tenderness threshold and were sympathetically predominant. Trunk muscle mass, pressure pain threshold, severity of central sensitization, and autonomic balance were significantly different between the clusters. Conclusions: Three characteristic subgroups were identified. The results contribute to treatment and prevention strategies for middle-aged and older adults with CLBP based on the characteristics of the subgroups rather than a uniform approach.

The pathogenesis of sarcopenia includes the dysfunction of calcium homeostasis associated with the sarcoplasmic reticulum; however, the localization in sarcoplasmic reticulum-related factors and differences by myofiber type remain unclear. Here, we investigated the effects of aging on sarcoplasmic reticulum-related factors in the soleus (slow-twitch) and gastrocnemius (fast-twitch) muscles of 3- and 24-month-old male C57BL/6J mice. There were no notable differences in the skeletal muscle weight of these 3- and 24-month-old mice. The expression of Atp2a1, Atp2a2, Sln, and Pln increased with age in the gastrocnemius muscles, but not in the soleus muscles. Subsequently, immunohistochemical analysis revealed ectopic sarcoplasmic reticulum calcium ion ATPase (SERCA) 1 and SERCA2a immunoreactivity only in the gastrocnemius muscles of old mice. Histochemical and transmission electron microscope analysis identified tubular aggregate (TA), an aggregation of the sarcoplasmic reticulum, in the gastrocnemius muscles of old mice. Dihydropyridine receptor α1, ryanodine receptor 1, junctophilin (JPH) 1, and JPH2, which contribute to sarcoplasmic reticulum function, were also localized in or around the TA. Furthermore, JPH1 and JPH2 co-localized with matrix metalloproteinase (MMP) 2 around the TA. These results suggest that sarcoplasmic reticulum-related factors are localized in or around TAs that occur in fast-twitch muscle with aging, but some of them might be degraded by MMP2.

Aging affects several tissues in the body, including skeletal muscle. Multiple types of collagens are localized in the skeletal muscle and contribute to the maintenance of normal muscle structure and function. Since the effects of aging on muscle fibers vary by muscle fiber type, it is expected that the effects of aging on intramuscular collagen might be influenced by muscle fiber type. In this study, we examined the effect of aging on collagen levels in the soleus (slow-twitch muscle) and gastrocnemius (fast-twitch muscle) muscles of 3-, 10-, 24-, and 28-month-old male C57BL/6J mice using molecular and morphological analysis. It was found that aging increased collagen I, III, and VI gene expression and immunoreactivity in both slow- and fast-twitch muscles and collagen IV expression in slow-twitch muscles. However, collagen IV gene expression and immunoreactivity in fast-twitch muscle were unaffected by aging. In contrast, the expression of the collagen synthesis marker heat shock protein 47 in both slow- and fast-twitch muscles decreased with aging, while the expression of collagen degradation markers increased with aging. Overall, these results suggest that collagen gene expression and immunoreactivity are influenced by muscle fiber type and collagen type and that the balance between collagen synthesis and degradation tends to tilt toward degradation with aging.