Manipulation of Ovarian Function Significantly Influenced Sarcopenia in Postreproductive-Age Mice

Previously, transplantation of ovaries from young cycling mice into old postreproductive-age mice increased life span. We anticipated that the same factors that increased life span could also influence health span. Female CBA/J mice received new (60 d) ovaries at 12 and 17 months of age and were evaluated at 16 and 25 months of age, respectively. There were no significant differences in body weight among any age or treatment group. The percentage of fat mass was significantly increased at 13 and 16 months of age but was reduced by ovarian transplantation in 16-month-old mice. The percentages of lean body mass and total body water were significantly reduced in 13-month-old control mice but were restored in 16- and 25-month-old recipient mice by ovarian transplantation to the levels found in six-month-old control mice. In summary, we have shown that skeletal muscle mass, which is negatively influenced by aging, can be positively influenced or restored by reestablishment of active ovarian function in aged female mice. These findings provide strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.

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Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Cells ◽

10.3390/cells10082169 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2169

Author(s):

Kyung-Ah Cho ◽

Da-Won Choi ◽

Yu-Hee Kim ◽

Jungwoo Kim ◽

Kyung-Ha Ryu ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Total Body Weight ◽

Activin A ◽

Dependent Manner ◽

Muscle Loss ◽

Total Body

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.

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Restoration of immune and renal function in aged females by re-establishment of active ovarian function

Reproduction Fertility and Development ◽

10.1071/rd16333 ◽

2017 ◽

Vol 29 (10) ◽

pp. 2052 ◽

Cited By ~ 4

Author(s):

Rhett L. Peterson ◽

Kate C. Parkinson ◽

Jeffrey B. Mason

Keyword(s):

Renal Function ◽

Ovarian Function ◽

Cell Subset ◽

Positive Influence ◽

Immune Functioning ◽

Control Female ◽

Ovarian Transplantation ◽

Gonadal Dysfunction ◽

Age Related ◽

Old Mice

Proper immune functioning is necessary to maximize reproductive success. In addition, age-associated uremia in women is often associated with hypothalamic–pituitary–gonadal dysfunction. In the present experiments, we tested immune and renal function to determine if exposure of postreproductive mice to young, reproductively cycling ovaries would influence non-reproductive physiological functions. Control female CBA/J mice were evaluated at 6, 13 and 16 months of age. Additional mice received new (60-day-old) ovaries at 12 months of age and were evaluated at 16 months of age. Consequently, 6-month-old control mice and 16-month-old recipient mice both possessed 6-month-old ovaries and were reproductively cycling. A significant age-related decline in immune function (T-cell subset analysis) was found in 16-month-old mice, but was improved 64% by ovarian transplantation. Renal function (blood urea nitrogen : creatinine ratio) was also decreased with aging, but ovarian transplantation restored function to levels found in 6-month-old mice. In summary, we have shown that immune and renal function, which are negatively influenced by aging, can be positively influenced or restored by re-establishment of active ovarian function in aged female mice. These findings provide a strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.

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Weight stability masks sarcopenia in elderly men and women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.2.e366 ◽

2000 ◽

Vol 279 (2) ◽

pp. E366-E375 ◽

Cited By ~ 259

Author(s):

Dympna Gallagher ◽

Else Ruts ◽

Marjolein Visser ◽

Stanley Heshka ◽

Richard N. Baumgartner ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Muscle Mass ◽

Fat Mass ◽

Skeletal Muscle Mass ◽

Measurement Techniques ◽

Elderly Subjects ◽

Elderly Men ◽

Total Body

Skeletal muscle loss or sarcopenia in aging has been suggested in cross-sectional studies but has not been shown in elderly subjects using appropriate measurement techniques combined with a longitudinal study design. Longitudinal skeletal muscle mass changes after age 60 yr were investigated in independently living, healthy men ( n = 24) and women ( n = 54; mean age 73 yr) with a mean ± SD follow-up time of 4.7 ± 2.3 yr. Measurements included regional skeletal muscle mass, four additional lean components (fat-free body mass, body cell mass, total body water, and bone mineral), and total body fat. Total appendicular skeletal muscle (TSM) mass decreased in men (−0.8 ± 1.2 kg, P = 0.002), consisting of leg skeletal muscle (LSM) loss (−0.7 ± 0.8 kg, P = 0.001) and a trend toward loss of arm skeletal muscle (ASM; −0.2 ± 0.4 kg, P = 0.06). In women, TSM mass decreased (−0.4 ± 1.2 kg, P = 0.006) and consisted of LSM loss (−0.3 ± 0.8 kg, P = 0.005) and a tendency for a loss of ASM (−0.1 ± 0.6 kg, P = 0.20). Multiple regression modeling indicates greater rates of LSM loss in men. Body weight in men at follow-up did not change significantly (−0.5 ± 3.0 kg, P = 0.44) and fat mass increased (+1.2 ± 2.4 kg, P = 0.03). Body weight and fat mass in women were nonsignificantly reduced (−0.8 ± 3.9 kg, P= 0.15 and −0.8 ± 3.5 kg, P = 0.12). These observations suggest that sarcopenia is a progressive process, particularly in elderly men, and occurs even in healthy independently living older adults who may not manifest weight loss.

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Skeletal muscle mass is associated with erythropoietin response in hemodialysis patients

BMC Nephrology ◽

10.1186/s12882-021-02346-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Tomoaki Takata ◽

Yukari Mae ◽

Kentaro Yamada ◽

Sosuke Taniguchi ◽

Shintaro Hamada ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Linear Regression Analysis ◽

Transferrin Saturation ◽

Resistance Index ◽

Hemodialysis Patients ◽

Maintenance Hemodialysis ◽

Weekly Dose

Abstract Background Hyporesponsiveness to erythropoietin stimulating agent (ESA) is associated with poor outcomes in patients with chronic kidney disease. Although ESA hyporesponsiveness and sarcopenia have a common pathophysiological background, clinical evidence linking them is scarce. The purpose of the study was to investigate the relationship between ESA responsiveness and skeletal muscle mass in hemodialysis patients. Methods This cross-sectional study analyzed 70 patients on maintenance hemodialysis who were treated with ESA. ESA responsiveness was evaluated by erythropoietin resistance index (ERI), calculated as a weekly dose of ESA divided by body weight and hemoglobin (IU/kg/week/dL), and a weekly dose of ESA/hemoglobin (IU/week/dL). A dose of ESA is equivalated to epoetin β. Correlations between ESA responsiveness and clinical parameters including skeletal muscle mass were analyzed. Results Among the 70 patients, ERI was positively correlated to age (p < 0.002) and negatively correlated to height (p < 0.001), body weight (p < 0.001), BMI (p < 0.001), skeletal muscle mass (p < 0.001), transferrin saturation (TSAT) (p = 0.049), and zinc (p = 0.006). In the multiple linear regression analysis, TSAT, zinc, and skeletal muscle mass were associated with ERI and weekly ESA dose/hemoglobin. Conclusions Skeletal muscle mass was the independent predictor for ESA responsiveness as well as TSAT and zinc. Sarcopenia is another target for the management of anemia in patients with hemodialysis.

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Body composition and energy intake — skeletal muscle mass is the strongest predictor of food intake in obese adolescents: The HEARTY trial

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0479 ◽

2016 ◽

Vol 41 (6) ◽

pp. 611-617 ◽

Cited By ~ 37

Author(s):

Jameason D. Cameron ◽

Ronald J. Sigal ◽

Glen P. Kenny ◽

Angela S. Alberga ◽

Denis Prud’homme ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Composition ◽

Body Weight ◽

Muscle Mass ◽

Energy Intake ◽

Skeletal Muscle Mass ◽

Fat Free Mass ◽

Cross Sectional ◽

Percentage Body Fat ◽

Obese Adolescents

There has been renewed interest in examining the relationship between specific components of energy expenditure and the overall influence on energy intake (EI). The purpose of this cross-sectional analysis was to determine the strongest metabolic and anthropometric predictors of EI. It was hypothesized that resting metabolic rate (RMR) and skeletal muscle mass would be the strongest predictors of EI in a sample of overweight and obese adolescents. 304 post-pubertal adolescents (91 boys, 213 girls) aged 16.1 (±1.4) years with body mass index at or above the 95th percentile for age and sex OR at or above the 85th percentile plus an additional diabetes risk factor were measured for body weight, RMR (kcal/day) by indirect calorimetry, body composition by magnetic resonance imaging (fat free mass (FFM), skeletal muscle mass, fat mass (FM), and percentage body fat), and EI (kcal/day) using 3 day food records. Body weight, RMR, FFM, skeletal muscle mass, and FM were all significantly correlated with EI (p < 0.005). After adjusting the model for age, sex, height, and physical activity, only FFM (β = 21.9, p = 0.007) and skeletal muscle mass (β = 25.8, p = 0.02) remained as significant predictors of EI. FFM and skeletal muscle mass also predicted dietary protein and fat intake (p < 0.05), but not carbohydrate intake. In conclusion, with skeletal muscle mass being the best predictor of EI, our results support the hypothesis that the magnitude of the body’s lean tissue is related to absolute levels of EI in a sample of inactive adolescents with obesity.

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