Sarcopenia is the degenerative loss of muscle mass and strength with aging. Although a role of mitochondrial metabolism in muscle function and in the development of many diseases has been described, the role of mitochondrial topology and dynamics in the process of muscle aging is not fully understood. This work shows a time line of changes in both mitochondrial distribution and skeletal muscle function during mice lifespan. We isolated muscle fibers from flexor digitorum brevis of mice of different ages. A fusion-like phenotype of mitochondria, together with a change in orientation perpendicular to the fiber axis was evident in the Adult group compared to Juvenile and Older groups. Moreover, an increase in the contact area between sarcoplasmic reticulum and mitochondria was evident in the same group. Together with the morphological changes, mitochondrial Ca2+ resting levels were reduced at age 10-14 months and significantly increased in the Older group. This was consistent with a reduced number of mitochondria-to-jSR pairs in the Older group compared to the Juvenile. Our results support the idea of several age-dependent changes in mitochondria that are accentuated in midlife prior to a complete sarcopenic phenotype.

2015—The purpose of this study was to determine the effects of short-term plyometric training interposed with 24 or 48 hours of rest between training sessions on explosive and endurance adaptations in young soccer players. A total of 166 players, between 10 and 17 years of age, were randomly divided into 3 groups: a control group (CG; n = 55) and 2 plyometric training groups with 24 hours (PT24; n = 54) and 48 hours (PT48; n = 57) of rest between training sessions. Before and after intervention, players were measured in squat jump, countermovement jump, 20 (RSI20) cm drop jump reactive strength index, broad long jump, 20-m sprint time, 10 × 5-m agility time, 20-m multistage shuttle run test, and sit-and-reach test. The plyometric training program was applied during 6 weeks, 2 sessions per week, with a load from 140 to 260 jumps per session, replacing some soccer-specific drills. After intervention, the CG did not show significant performance changes. PT24 and PT48 groups showed a small-to-moderate significant improvement in all performance tests (p < 0.001), with no differences between treatments. Although it has been recommended that plyometric drills should not be conducted on consecutive days, the study shows that plyometric training applied twice weekly on consecutive or nonconsecutive days results in similar explosive and endurance adaptations in young male soccer players....

Background: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. Methods: We evaluated the effects of DCA and CA on mitochondrial alterations in C₂C₁₂ myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. Results: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. Conclusion: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.

The micropeptide adropin encoded by the clock-controlled Energy homeostasis-associated gene is implicated in the regulation of glucose metabolism. However, its links to rhythms of nutrient intake, energy balance and metabolic control remains poorly defined. Using surveys of Gene Expression Omnibus datasets, we confirm that fasting suppresses liver adropin expression in lean C57L/6J (B6) mice. However, circadian rhythm data are inconsistent. In lean mice, CR induces bouts of compulsive binge feeding separated by prolonged fasting intervals, increasing NAD-dependent deacetylase sirtuin-1 signaling important for glucose and lipid metabolism regulation. CR upregulates adropin expression and induces rhythms correlating with cellular stress-response pathways. Furthermore, adropin expression correlates positively wth phosphoenolpyruvate carboxokinase-1 (Pck1) expression, suggesting a link with gluconeogenesis. Our previous data suggest that adropin suppresses gluconeogenesis in hepatocytes. Liver-specific adropin knockout (LAdrKO) mice exhibit increased glucose excursions following pyruvate injections, indicating increased gluconeogenesis. Gluconeogenesis is also increased in primary cultured hepatocytes derived from LAdrKO mice. Analysis of circulating insulin levels and liver expression of fasting-responsive PKA signaling pathways also suggests enhanced responses in LAdrKO mice during a glucagon tolerance test (250 μg/kg ip.). Fasting-associated changes in PKA signaling are attenuated in transgenic mice constitutively expressing adropin, and in fasting mice treated acutely with adropin peptide. In summary, hepatic adropin expression is regulated by nutrient- and clock-dependent extrahepatic signals. CR induces pronounced post-prandial peaks in hepatic adropin expression. Rhythms of hepatic adropin expression appear to link rhythms in energy balance and cellular stress to the intracellular signal transduction pathways that drive the liver fasting response.