Epidemiological findings suggest that the pathogenesis and mortality rates of many age-related diseases are associated with sarcopenia, a condition defined as age-associated muscle weakening and atrophy. Skeletal muscle plays important roles beyond bodily movement, including modulating metabolic homeostasis in response to environmental changes. Skeletal muscle has great metabolic plasticity that enables it to modify its fiber-type composition to suit nutritional, state, and environmental changes. Aging brings a gradual decline in the metabolic plasticity of muscle. Deciphering the mechanisms of muscular metabolic adaptation can enable us to develop a better understanding of sarcopenia and assist in the development of early diagnostic tools as well as effective dietary and exercise intervention programs.
People are exposed to various acute and chronic stressors in daily life. Usually, blood pressure increases quickly in response to acute physical and psychological stressors. The pressor response to acute stress is explained primarily by cardiovascular regulatory mechanisms of the sympathetic nervous and endothelial systems. It has been found, by long-term follow-up studies across a wide range of generations, that exaggerated blood pressure reactivity to acute stress is an independent risk factor for cardiovascular disease (CVD), including hypertension. The association between exaggerated blood pressure reactivity to acute stress and increased future CVD risk may be explained by sympathetic effects, mechanical effects, and prothrombotic changes. Consequently, it is possible that stress management, such as cognitive behavioral therapy and improvement in the psychosocial environment, may be effective, at least in part, against future CVD due to the weakening of stress-induced blood pressure reactivity from childhood to adulthood.
The expression of cell lineage-specific genes during cell differentiation and development is regulated by lineage-specific transcription factors. Recent studies have revealed that epigenetic mechanisms, including post-translational modifications in histone proteins and DNA methylation, play important roles in cell lineage determination and further differentiation. Many different post-translational modifications of histone proteins have been identified to date. For example, modifications at the N-terminal ninth lysine residue of histone H3 (H3K9) are associated with the level of gene expression and local chromatin structure. H3K9 is known to have un-, mono-, di-, and trimethylation states, and these methylated states are determined by six H3K9 methyltransferases in mammals. Among these H3K9 methyltransferases, G9a is responsible for mono- and dimethylation of H3K9. G9a-null mice showed embryonic lethality, indicating its critical roles in cell differentiation, organogenesis, and development. Indeed, studies of G9a conditional deletion in vivo and G9a-deficient cells in vitro have suggested that G9a is a multifunctional protein in various cell types. This short review summarizes recent findings regarding the effects of G9a function on the development of mesenchymal tissues, such as muscle, adipose, and skeletal tissues.
In this review, we discuss the morphologic influence of clenbuterol on muscle atrophy with particular focus on cast-immobilization used in surgical care. β2-agonists induce muscle hypertrophy, particularly in fast muscles. Similar to these anabolic actions, the β2-agonist clenbuterol attenuates immobilization-induced atrophy in fast muscles. Furthermore, the attenuating effects of this agonist on muscle atrophy may be related to its preventative effect in fast muscle fibers.
Clenbuterol (CB) is one of the β2-adrenergic receptor agonists with powerful muscle anabolic and lipolytic effects, and is prohibited as a doping drug for athletes. However, it is one of the candidate countermeasures for aging-related diseases. Previously we reported that CB induced muscular hypertrophy, but inhibited the longitudinal growth of bones in young male rats. However, the mechanism of the inhibitory effect on bone growth is not yet clear. CB is manufactured as a 1:1 racemic mixture of 2 isomers of (-)-R and (+)-S enantiomers, and only the (-)-R enantiomer may have pharmacological activity. We examined the effects of two CB enantiomers, (+)-S-CB and (-)-R-CB, on growth of striated muscle and bone in young male rats. Eighteen male Sprague-Dawley rats (8-wk-old) were randomly assigned to a control (CONT, n = 6) and two CB enantiomers groups ((+)-S-CLEB: n=6, (-)-R-CLEB: n=6). Each CB enantiomer of 2 mg/kg body weight was daily administered subcutaneously for 2 weeks. After treatment, heart and the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles and bones were analyzed. The muscle wet weights of SOL and EDL muscles significantly increased in (+)-S-CLEB (HEART: +28%, SOL: +25%, EDL: +28%) and (-)-R-CLEB (HEART: +27%, SOL: +29%, EDL: +35%). Both (+)-S-CB and (-)-R-CB induced striated muscle hypertrophy (heart, SOL, and EDL). Concerning bones, (+)-S-CB induced decreased tibia length (-1.2%) and decreased femur BMD (-5.8%), and (-)-R-CB induced decreased femur BMD (-8.2%). These results show that (+)-S-CB and (-)-R-CB might work differently at times.
To establish an efficient method of enhancing mitochondrial biogenesis, we investigated the effect of casein peptide supplementation. The aim of this study was to examine whether oral casein peptide ingestion enhances exercise-induced mitochondrial adaptation in high fat diet-induced obese diabetes mice. Mice received either casein peptide or water (0.2 mg/g body weight, 7 times/week) and were subjected to treadmill running (20–25 m/min × 60 min, 5 times/week for 6 weeks) 30 min later. In plantaris muscle (higher proportion of fast-twitch muscle fibers), casein peptide treatment did not impact mitochondrial adaptation. However, in soleus muscle (higher proportion of slow-twitch muscle fibers) and heart, casein peptide supplementation with exercise increased mitochondrial enzyme activity (citrate synthase and β-hydroxyacyl CoA dehydrogenase activity). To clarify the mechanisms underlying mitochondrial adaptation enhancement, we investigated the acute effects of pre-exercise casein peptide ingestion on the phosphorylation status of cellular signaling cascades associated with mitochondrial adaptations. We observed that casein peptide ingestion boosted exercise-induced AMPK phosphorylation in soleus, but not plantaris muscle. Thus, our present investigation suggested that casein peptide ingestion enhanced exercise-induced mitochondrial adaptation in slow twitch muscle, but not fast twitch muscle in high fat diet-induced obese-diabetes mice.