Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.

Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned to one of the three experimental groups: nonimmobilization control group (sterilized water injection), immobilization control group (sterilized water injection), and immobilization and MOTS-c-treated group (15 mg/kg/day MOTS-c injection). We used casting tape for the immobilization experiment. After 8 days of the experimental period, skeletal muscle samples were collected and used for Western blotting, RNA sequencing, and lipid and collagen assays. Immobilization reduced ∼15% of muscle mass, whereas MOTS-c treatment attenuated muscle loss, with only a 5% reduction. MOTS-c treatment also normalized phospho-AKT, phospho-FOXO1, and phospho-FOXO3a expression levels and reduced circulating inflammatory cytokines, such as interleukin-1b (IL-1ß), interleukin-6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1), in immobilized mice. Unbiased RNA sequencing and its downstream analyses demonstrated that MOTS-c modified adipogenesis-modulating gene expression within the peroxisome proliferator-activated receptor (PPAR) pathway. Supporting this observation, muscle fatty acid levels were lower in the MOTS-c-treated group than in the casted control mice. These results suggest that MOTS-c treatment inhibits skeletal muscle lipid infiltration by regulating adipogenesis-related genes and prevents immobilization-induced muscle atrophy.NEW & NOTEWORTHY MOTS-c, a mitochondrial microprotein, attenuates immobilization-induced skeletal muscle atrophy. MOTS-c treatment improves systemic inflammation and skeletal muscle AKT/FOXOs signaling pathways. Furthermore, unbiased RNA sequencing and subsequent assays revealed that MOTS-c prevents lipid infiltration in skeletal muscle. Since lipid accumulation is one of the common pathologies among other skeletal muscle atrophies induced by aging, obesity, cancer cachexia, and denervation, MOTS-c treatment could be effective in other muscle atrophy models as well.

Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined via in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was significantly stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs are closer to those in humans than to those in mice.

A longitudinal study of handgrip strength asymmetry.

OBJECTIVE: The previous results from cross-sectional studies indicate that there could be alterations across time in handgrip strength (HGS) asymmetry. One way to investigate this is to test the same children multiple times. Therefore, we aimed to evaluate the laterality of HGS in healthy young children at two different time points separated by a year. METHODS: A total of 165 preschool children (79 males and 87 females) between the ages of 4.5 and 5.6 years participated and performed maximal voluntary HGS in both hands using a Smedley handgrip dynamometer. We ran a paired sample t-test on the difference scores (right - left vs. right - left) to determine if HGS (right vs. left) differed across time. RESULTS: The difference between hands (t = -4.804, p < .0001) did differ between time points. At the initial test, the mean value of the HGS in the right hand was approximately 15% higher than that of the left hand. This difference between hands was reduced following a year. The mean bias between tests (second test - initial test) and the 95% limits of agreement was -0.84 (-5.27, 3.58) kg. CONCLUSION: Contrary to our hypothesis, HGS asymmetry during the initial test (at age 5) was not observed in the second test completed a year later (at age 6). These results suggest that HGS asymmetry is uncertain in children between 5 and 6 years. In this short-term study, it was impossible to ascertain when HGS asymmetry first appeared. Longer term studies are required to better determine when these changes occur.

Serum albumin levels as a predictive biomarker for low-load resistance training programs' effects on muscle thickness in the community-dwelling elderly Japanese population: interventional study result.

BACKGROUND: Resistance training has been recommended as an effective measure against age-related loss of muscle mass and muscle strength, called sarcopenia, even in older adults. However, despite subjecting each participant to the same training program, the training effect solely depended on the individual. This study aimed to evaluate whether certain blood parameters influenced the effect of a low-load resistance training program on muscle thickness in the community-dwelling elderly population. METHODS: Sixty-nine community-dwelling Japanese (49 women and 20 men) subjects aged 69.4 ± 6.5 years were included. Low-load resistance training was performed twice a week for 12 weeks. Muscle thickness at the anterior aspects of the thigh (AT) was measured using a B-mode ultrasound device, and 22 blood parameter levels were assessed before and after the program. We checked the first quartile value of each parameter to establish cutoff values, and participants were divided into low or normal groups for each parameter. RESULTS: A low-load resistance training program significantly increased muscle thickness at the AT. The interaction between time and groups was examined at low (< 4.1 g/dL) versus normal (≥ 4.1 g/dL) serum albumin (Alb) levels. Although there was no difference in muscle thickness at the AT before the training intervention, the hypertrophic effects were higher in the normal serum Alb level group than in the low serum Alb level group. The binomial logistic regression analysis showed that participants in the low serum Alb group had an odds ratio of 7.08 for decreased muscle thickness at the AT. The effect of a low-load resistance training program on lower limb muscle thickness appears to be limited in participants with low serum Alb levels before training interventions. CONCLUSIONS: Serum Alb level may act as a biomarker to predict the effects of low-load resistance training programs on muscle hypertrophy in elderly individuals. TRIAL REGISTRATION: This study was retrospectively registered in UMIN-Clinical Trial Registry (CTR), ID: UMIN000042759 (date of registration, 14 Dec 2020).

The 30-s chair stand test can be a useful tool for screening sarcopenia in elderly Japanese participants.

BACKGROUND: Low muscle strength has been focused on as an essential characteristic of sarcopenia, and the 30-s chair stand test (CS-30) could be a particularly useful test for assessing muscle strength. While it is speculated to be a beneficial tool for the assessment of sarcopenia, this remains to be verified. In this study, we examined the reliability and optimal diagnostic score of the CS-30 for assessing sarcopenia in elderly Japanese participants. METHODS: This cross-sectional study included 678 participants (443 females and 235 males) who underwent the test for sarcopenia as per the Asian Working Group for Sarcopenia (AWGS) 2019, the CS-30 test, and the isometric knee-extension muscle strength test. ROC analysis was used to estimate the optimal CS-30 scores at which sarcopenia was detected. RESULTS: CS-30 scores were positively associated with sarcopenia (OR: 0.88; 95% CI:0.82-0.93). The AUC of the CS-30 for sarcopenia definition were 0.84 (p < 0.001) for females and 0.80 (p < 0.001) for males. The optimal number of stands in the CS-30 that predicted sarcopenia was 15 for females (sensitivity, 76.4%; specificity, 76.8%) and 17 for males (sensitivity, 75.0%; specificity, 71.7%). CONCLUSIONS: The CS-30 was found to be a reliable test for sarcopenia screening in the elderly Japanese population.

Site-Specific Muscle Loss in the Abdomen and Anterior Thigh in Elderly Males with Locomotive Syndrome.

Although locomotive syndrome (LS) is a condition of reduced mobility, little information is available regarding the loss of site-specific skeletal muscle mass. The aim of the present study is to examine site-specific muscle loss in elderly males with LS. A total of 100 men ranging in age from 65 to 74 years were divided into two groups (LS and non-LS) using LS risk tests including the stand-up test, two-step test, and the 25-question geriatric locomotive function scale Muscle thickness (MTH) at eight sites-anterior and posterior thigh (AT and PT, respectively), anterior and posterior lower leg (AL and PL, respectively), rectus abdominis (RA), anterior and posterior upper arm (AU and PU, respectively), and anterior forearm (AF)-was evaluated using B-mode ultrasound. Furthermore, the 30-s chair stand test (CS-30), 10-m walking time, zig-zag walking time, and sit-up test were assessed as physical functions. There were no significant differences in age and body mass index between the LS and non-LS groups. The percentage of skeletal muscle was lower in the LS group than in the non-LS group. Although there were no differences in the MTH of AU, PU, AF, PT, Al and PL, site-specific muscle loss was observed at RA and AT in the LS group. CS-30, 10-m walking time, zig-zag walking time, and sit-up test in the LS group were all worse than those in the non-LS group. The MTHs of RA and AT were both correlated to those physical functions. In conclusion, the LS group had site-specific muscle loss and worse physical functions. This study suggests that site-specific changes may be associated with age-related physical functions. These results may suggest what the essential characteristics of LS are.

Muscle Size and Strength of the Lower Body in Supervised and in Combined Supervised and Unsupervised Low-Load Resistance Training.

This study aimed to clarify whether low-load resistance training at a low frequency (twice a week) using body weight and elastic band improves muscle size, muscle strength, and physical functions and to compare the training effects between supervised training and a combination of supervised and unsupervised training in untrained older adults. Fifty-one older adults (ages: 57-75 years) selected to either a supervised (S) training group (n = 34) or a combined supervised and unsupervised (SU) group (n = 17). Both groups performed low-load resistance training composed of nine exercises for 12 weeks. The S group participated in supervised exercise sessions twice a week, and the SU group performed a supervised exercise session once a week and an unsupervised exercise session at home also once a week. For muscle thicknesses in the anterior aspects of the forearm, upper arm, and thigh and the posterior aspect of the thigh, group × time interactions were observed (p < 0.05). The hypertrophic effects were higher in the S group. Isometric knee extension strength and physical functions increased similarly in both groups. Low-load resistance training using body weight and elastic band twice a week for 12 weeks induces muscle hypertrophy and increases muscle strength and physical functions in older adults. Although the muscle hypertrophic effects are greater in the S group than in the SU group, the other effects were similar between the groups.

Association between locomotive syndrome and blood parameters in Japanese middle-aged and elderly individuals: a cross-sectional study.

BACKGROUND: Locomotive syndrome (LS) is associated with weakness and loss of function in the musculoskeletal organs. We aimed to determine the association between LS components and blood parameters in middle-aged and elderly individuals. METHODS: We included 223 middle-aged and elderly individuals in this study (104 men and 119 women; age: 40-85 years). All participants were asked to fast for at least 3 h before the venous blood samples were obtained and the hemoglobin, total protein, glycated hemoglobin (HbA1c), growth hormone, albumin and lipid profile were measured. Three functional tests, the stand-up test, the two-step test, and the 25-question geriatric locomotive function scale (GLFS) were used to assess the risk of LS. Walking speed was assessed by the 10-m walking test. Maximal isometric muscle strengths of the knee extensors were examined, and the weight bearing index (knee extension strength/body weight) was calculated. To assess an independent association between blood parameters and LS, the area under the receiver operating characteristic curve analysis (area under the curve, sensitivity, and specificity) and a binary logistic regression analysis were performed with adjustment for age. RESULTS: Of the 223 subjects, 119 (53.3%) fulfilled the diagnostic criteria for LS (including a two-step test score < 1.3, difficulty with one-leg standing from 40 cm in the stand-up test, and a 25-question GLFS score ≥ 7). Increased levels of HbA1c were significant risk factors for LS with an OR of 2.62 (OR95%CI = 1.43-4.80), as determined by a logistic regression analysis. Additionally, dehydroepiandrosterone-sulfate (DHEA-S) levels were significant only in the male subjects (OR = 0.992 [OR95%CI = 0.986-0.998]), at a threshold of 88 (AUC; 0.70, sensitivity; 79.6%, specificity; 49.1%). Moreover, 101 of 223 participants (41 men, 60 women) were analyzed for serum albumin levels, with a prevalence of LS at 55.4%, indicating that low levels of albumin were significant risk factors for LS (OR = 0.148 [OR95%CI = 0.023-0.954], p = 0.0445). CONCLUSIONS: These results suggest that higher HbA1c and lower albumin are associated with the prevalence of LS in Japanese middle-aged and elderly individuals. Furthermore, low DHEA-S levels may be useful screening tools for LS in men.

Effects of Progressive Walking and Stair-Climbing Training Program on Muscle Size and Strength of the Lower Body in Untrained Older Adults.

The purpose of the present study was to investigate the effect of the progressive walking program on lower limb muscle size and strength and evaluated whether the stair-climbing exercise provided additional training effects when combined with the walking program. Fifteen elderly subjects (age 69 ± 1 years, height 1.63 ± 0.02 m, body weight 64.5 ± 2.0 kg) were randomly assigned to a walking group or a walking and stair-climbing group. The progressive walking program comprised continuous (week 1-8) and interval (week 9-17) exercises. The walking and stair-climbing group also performed stair climbing. Muscle thickness, strength, and walking performance were evaluated before and 8 and 17 weeks after the start of the program. The muscle thickness of the anterior and posterior parts of the thigh significantly (p < 0.05) increased in both groups. There was also a significant (p < 0.01) main effect of time in isometric maximal strength and the values expressed relative to body mass for both knee extension and flexion. However, no group × time interactions were noted. Furthermore, the percentage change of knee flexion strength after the training period was significantly (p < 0.01) correlated with the pre-intervention value. Seventeen weeks of the progressive walking program can increase thigh muscle size and strength for older adults; however, an added stair-climbing exercise may not provide additional training effects. Furthermore, the magnitude of improvement in knee flexion strength would depend on the pre-intervention value.

Effects of training intensity in electromyostimulation on human skeletal muscle.

PURPOSE: High-intensity neuromuscular electrical stimulation (NMES) training can induce muscle hypertrophy at the whole muscle and muscle fiber levels. However, whether low-intensity NMES training has a similar result is unknown. This study aimed to investigate whether low-intensity NMES training could elicit muscle hypertrophy at the whole muscle and muscle fiber levels in the human skeletal muscle. METHODS: Eight untrained young males were subjected to 18 min of unilateral NMES training for 8 weeks. One leg received NMES at maximal tolerable intensity (HIGH); the other leg received NMES at an intensity half of that in the HIGH condition (LOW). Quadriceps muscle thickness (MT), muscle fiber cross-sectional area (CSA), and knee extension strength were measured before and after the training period. RESULTS: The average training intensity throughout the intervention period in the HIGH and LOW conditions were 62.5 ± 4.6% maximal voluntary contraction (MVC) and 32.6 ± 2.6% MVC, respectively. MT, CSA, and muscle strength increased in both exercise conditions (p < 0.05); however, training effects in the LOW condition were lower than those in the HIGH condition (p < 0.05). The average training intensity showed a positive correlation with percent changes in muscle strength (r = 0.797, p = 0.001), MT (r = 0.876, p = 0.001), type I fiber CSA (r = 0.730, p = 0.01), and type II fiber CSA (r = 0.899, p = 0.001). CONCLUSIONS: Low-intensity NMES could increase MT, muscle fiber CSA, and muscle strength in healthy human skeletal muscles. However, the magnitude of increase is lower in low-intensity than in high-intensity NMES training.

Effects of drop sets with resistance training on increases in muscle CSA, strength, and endurance: a pilot study.

To investigate the effects of a single high-load (80% of one repetition maximum [1RM]) set with additional drop sets descending to a low-load (30% 1RM) without recovery intervals on muscle strength, endurance, and size in untrained young men. Nine untrained young men performed dumbbell curls to concentric failure 2-3 days per week for 8 weeks. Each arm was randomly assigned to one of the following three conditions: 3 sets of high-load (HL, 80% 1RM) resistance exercise, 3 sets of low-load [LL, 30% 1RM] resistance exercise, and a single high-load (SDS) set with additional drop sets descending to a low-load. The mean training time per session, including recovery intervals, was lowest in the SDS condition. Elbow flexor muscle cross-sectional area (CSA) increased similarly in all three conditions. Maximum isometric and 1RM strength of the elbow flexors increased from pre to post only in the HL and SDS conditions. Muscular endurance measured by maximum repetitions at 30% 1RM increased only in the LL and SDS conditions. A SDS resistance training program can simultaneously increase muscle CSA, strength, and endurance in untrained young men, even with lower training time compared to typical resistance exercise protocols using only high- or low-loads.

Effects of a progressive walking program on the risk of developing locomotive syndrome in elderly Japanese people: a single-arm trial.

[Purpose] This study aimed to identify the efficacy of a progressive walking program on the risk of developing locomotive syndrome among untrained elderly Japanese people. [Participants and Methods] Twenty-four untrained elderly individuals (68 ± 4 years) completed a 17-week progressive walking program. The stand-up, two-step tests and the 25-question geriatric locomotive function scale were used to assess the risk of locomotive syndrome at baseline, the 8-week midpoint (2 months), and the 17-week endpoint (4 months). Maximal isometric muscle strength of the knee extensors and flexors were measured using a dynamometer with the hip joint angle at 90° of flexion and physical function (the 30-s sit-to-stand, sit-up, 10-meter walk, and grip strength) were evaluated. [Results] The 4-month walking program significantly improved the two-step test and geriatric locomotive function scale scores. This may be attributable to the improvement in knee flexor strength and physical function. [Conclusion] A 4-month program of progressive walking effectively lowered the risk of developing locomotive syndrome in elderly Japanese people by improving knee flexor muscle strength and physical function.

Skeletal Muscle-Derived Stem Cell Transplantation Accelerates the Recovery of Peripheral Nerve Gap Injury under 50% and 100% Allogeneic Compatibility with the Swine Leucocyte Antigen.

Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45- (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.

Relationship between Skeletal Muscle Thickness and Physical Activity in 4- to 6-Year-Olds in Japan.

PURPOSE: Physical activity (PA) is widely recognized as a key factor in promoting skeletal muscle growth, though little is known about the specific impact of PA on the skeletal muscle development of preschool children. The purpose of this study is to investigate whether there is a relationship between PA levels and skeletal muscle thickness in preschoolers. By exploring this relationship, we hope to gain a better understanding of how PA can be used to promote healthy skeletal muscle development in preschoolers. METHODS: In this study, a total of 275 healthy Japanese preschoolers, aged 4-6 years, from seven nursery schools in the town of Togo were recruited. Participants were asked to wear an accelerometer for four consecutive days to record their daily steps and the amount of time spent in moderate-to-vigorous PA and t total physical activity. Muscle thickness (MTs) was measured using B-mode ultrasonography at four sites: the anterior and posterior thigh (AT and PT, respectively) and the anterior and posterior lower leg (AL and PL, respectively). RESULTS: On weekdays, boys were found to be more physically active and engaged in significantly higher levels of total physical activity and moderate-to-vigorous PA than girls. Both boys and girls recorded more physical activity, daily steps, and higher levels of total physical activity and MVPA on weekdays compared to weekends. After adjusting for daylight duration, multivariable regression analyses revealed that increased total physical activity and moderate-to-vigorous PA were positively associated with greater muscle thickness size in the anterior tibialis (AT) and posterior lower leg (PL) muscles (ß = 1.11 and ß = 1.37 for AT, ß = 1.18 and ß = 0.94 for PL, p < 0.05) in Japanese preschoolers. CONCLUSIONS: The time spent involved in most of the different categories of moderate-to-vigorous PA was significantly higher for boys than for girls on the weekdays and weekends. Additionally, there was a positive correlation between time spent in moderate-to-vigorous PA and greater development of skeletal muscle in the lower body.

Associations of Morphological Changes in Skeletal Muscles of Preschool Children in China Following Physical Activity.

PURPOSE: Physical activity (PA) is likely to be the most important modifiable factor in skeletal muscle development. However, the influence of PA on the skeletal muscle of preschool children has not been thoroughly investigated. The main objective of this study was to quantitatively measure PA, and then, to assess whether associations exist between site-specific muscle changes and PA in relation to sex and weight statuses in preschool children aged 3 to 4 years. METHODS: A total of 86 healthy preschool children, aged 3-4 years, were instructed to wear an accelerometer for seven consecutive days. The number of steps taken daily, and minutes spent in moderate-vigorous PA (MVPA) and total PA (TPA) were recorded. Muscle thickness was measured by B-mode ultrasonography using a 5-18 MHz scanning head. Muscle thickness was measured at seven sites: the lateral forearm, upper arm, abdomen, anterior and posterior thigh, and anterior and posterior lower leg. RESULTS: There was no significant difference between boys and girls in terms of MVPA and TPA on weekdays and weekends. According to the linear regression models, after adjusting for daylight duration, the muscle of the posterior thigh was significantly positively associated (p < 0.05) with daily steps and MVPA on weekdays for boys and girls, respectively. CONCLUSIONS: We found that the muscle thickness of the posterior thigh in preschool children was significantly positively associated with PA, as measured by daily steps and MVPA. We suggest that for the overall health and well-being of preschool children, the levels of PA should be maintained and/or increased, and preferably transformed into a regular part of daily living.

Correction: Ishihara et al. Association between Daily Physical Activity and Locomotive Syndrome in Community-Dwelling Japanese Older Adults: A Cross-Sectional Study. Int. J. Environ. Res. Public Health 2022, 19, 8164.

There was an error in the "d-value of the first paragraph in Section 3 (Results)" in the original publication (Page 5, Line 41) [...].

Loquat Leaf Extract Enhances Muscle Contraction-Induced Activation of Protein Synthesis Signaling in Rat Skeletal Muscle.

Loquat (Eriobotrya japonica (Thunb.) Lindl.) leaves are traditionally used to improve muscle weakness, but their effects on muscle protein synthesis require further research. Therefore, we aimed to investigate whether loquat leaf extract (LLE) enhances muscle contraction-induced activation of muscle protein synthesis signaling. Male Wistar rats (12 weeks old, n = 6/group) were categorized into water treatment (CON) and LLE treatment (LLE) groups. The rats were administered distilled water or LLE (1.5 g/kg/day) once a day by oral gavage for 7 days. On day 7, at 3 h post-LLE administration, the gastrocnemius muscle in the right leg of each rat was stimulated by electrical muscle stimulation (EMS) (100 Hz, 30 V) through five sets of 10 isometric contractions (7 s contraction, 3 s rest) with 3 min interset intervals. The rats were then sacrificed, and the gastrocnemius muscles of both legs were excised at 3 h post-EMS. The phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway molecules (Akt, mTOR, and p70S6K) were determined by Western blotting. Regarding the muscle contraction-induced protein synthesis signaling pathway, Akt phosphorylation at Ser473 was not significantly different between the CON and LLE groups. mTOR phosphorylation at Ser2448 was increased by EMS but did not show a significant difference between the CON and LLE groups. p70S6K phosphorylation at Thr389 was significantly increased in response to EMS, whereas the LLE group showed significantly higher p70S6K phosphorylation at Thr389 than that in the CON group. This suggests that LLE enhances muscle contraction-induced activation of p70S6K phosphorylation in rat skeletal muscles.

Quantitative Evaluation of the Reduced Capacity of Skeletal Muscle Hypertrophy after Total Body Irradiation in Relation to Stem/Progenitor Cells.

The effects of total body irradiation (TBI) to the capacity of skeletal muscle hypertrophy were quantified using the compensatory muscle hypertrophy model. We additionally assessed the responses of stem and/or progenitor cells in the muscles. A single TBI of 9.0, 5.0 and 2.5 Gy was delivered to C57BL/6 mice. Bone marrow stromal cells were obtained from GFP-Tg mice, and were injected into the tail vein of the recipient mice (1 × 106 cells/mouse), for bone marrow transplantation (BMT). Five weeks after TBI, the mean GFP-chimerism in the blood was 96 ± 0.8% in the 9 Gy, 83 ± 3.9% in the 5 Gy, and 8.4 ± 3.4% in the 2.5 Gy groups. This implied that the impact of 2.5 Gy is quite low and unavailable as the BMT treatment. Six weeks after the TBI/BMT procedure, muscle hypertrophy was induced in the right plantaris muscle by surgical ablation (SA) of the synergist muscles (gastrocnemius and soleus), and the contralateral left side was preserved as a control. The muscle hypertrophy capacity significantly decreased by 95% in the 9 Gy, 48% in the 5 Gy, and 36% in the 2.5 Gy groups. Furthermore, stem/progenitor cells in the muscle were enzymatically isolated and fractionated into non-sorted bulk cells, CD45-/34-/29+ (Sk-DN), and CD45-/34+ (Sk-34) cells, and myogenic capacity was confirmed by the presence of Pax7+ and MyoD+ cells in culture. Myogenic capacity also declined significantly in the Bulk and Sk-DN cell groups in all three TBI conditions, possibly implying that skeletal muscles are more susceptible to TBI than bone marrow. However, interstitial Sk-34 cells were insusceptible to TBI, retaining their myogenic/proliferative capacity.

Circadian rhythms modulate the effect of eccentric exercise on rat soleus muscles.

We investigated whether time-of-day dependent changes in the rat soleus (SOL) muscle size, after eccentric exercises, operate via the mechanistic target of rapamycin (mTOR) signaling pathway. For our first experiment, we assigned 9-week-old male Wistar rats randomly into four groups: light phase (zeitgeber time; ZT6) non-trained control, dark phase (ZT18) non-trained control, light phase-trained, and dark phase-trained. Trained animals performed 90 min of downhill running once every 3 d for 8 weeks. The second experiment involved dividing 9-week-old male Wistar rats to control and exercise groups. The latter were subjected to 15 min of downhill running at ZT6 and ZT18. The absolute (+12.8%) and relative (+9.4%) SOL muscle weights were higher in the light phase-trained group. p70S6K phosphorylation ratio was 42.6% higher in the SOL muscle of rats that had exercised only in light (non-trained ZT6). Collectively, the degree of muscle hypertrophy in SOL is time-of-day dependent, perhaps via the mTOR/p70S6K signaling.

Association between Daily Physical Activity and Locomotive Syndrome in Community-Dwelling Japanese Older Adults: A Cross-Sectional Study.

This study aimed to evaluate the association between locomotive syndrome (LS) and daily physical activity (PA) in community-dwelling older adults. This cross-sectional study included 80 healthy Japanese older adults (40 men and 40 women; age: 60-79 years). Habitual daily PA was evaluated using a triaxial wrist accelerometer. Participants were divided into two groups based on the results of the two-step test, stand-up test, and 25-question geriatric locomotive function scale. Binomial logistic regression analysis was conducted to examine the statistical relationships between daily PA and category of LS, adjusting for age from adjusted odds ratio (adjusted OR) with the 95 percent confidence intervals (95%CI) and bootstrap 95%CI. The mean step count and time spent on moderate to vigorous physical activity (MVPA) were significantly higher among non-LS participants than among LS participants in women, but not in men. Logistic regression analyses indicated that spending longer than 28 min/day on MVPA was significantly associated with a lower likelihood of LS relative to short time category under 28 min/day in women (adjusted OR = 0.12, 95%CI = 0.02-0.59, bootstrap 95%CI = 0.01-0.43), but not in men. This study suggests that in community-dwelling older women, those with higher MVPA had lower odds of LS, and daily MVPA was associated with LS, but not in men. Therefore, the associations between LS and daily physical activity were partly dependent on sex differences.