The aging myostatin null phenotype: reduced adiposity, cardiac hypertrophy, enhanced cardiac stress response, and sexual dimorphism
| Autor: | James B. Stanton, Dor Dor Vang, Dung Luong, Melissa F. Jackson, Buel D. Rodgers, Dilip K. Garikipati, O. Lynne Nelson |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cardiac function curve Aging Cardiac output medicine.medical_specialty Cardiotonic Agents Time Factors Endocrinology Diabetes and Metabolism Adipose tissue Cardiomegaly Myostatin Kidney Fat pad Mice Sex Factors Endocrinology Adipose Tissue Brown Bone Density Heart Rate Internal medicine medicine Animals Muscle Skeletal Adiposity Ultrasonography Mice Knockout biology Myocardium Isoproterenol Kidney metabolism Organ Size medicine.disease Mice Inbred C57BL Phenotype Heart failure Sarcopenia Heart Function Tests biology.protein Regression Analysis Female Spleen |
| Zdroj: | Journal of Endocrinology. 213:263-275 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1530/joe-11-0455 |
| Popis: | The natural aging process results in the physiological decline of multiple tissues and organ systems. Changes commonly occur with middle age and include decreased skeletal muscle mass, bone mineral density, cardiac output, and insulin sensitivity, and increased adiposity, all of which can contribute to the onset of sarcopenia, osteoporosis, heart failure, or type 2 diabetes. Recent studies suggest that myostatin may influence many of these systems. We therefore sought to determine whether they are affected by aging, especially in ‘middle-aged’Mstn−/−mice (12–20 months old (m.o.)). Although body weights were similar in wild-type (WT) andMstn−/−mice, lean fat-free mass and skeletal muscles composed of predominantly type I, II, and mixed fibers were significantly heavier inMstn−/−mice. These differences were accompanied by lower total adiposity, especially in female mice, white and brown fat pad weights, and adipocyte size. Hearts were heavier inMstn−/−mice across a large age range (3–24 m.o.) and exhibited signs of dilated cardiomyopathy at rest, which include lower strain measurements compared with WT myocardium. However,Mstn−/−mice responded better to isoproterenol stress tests with greater increases in fractional shortening and ejection fraction—differences that were again more apparent in females and which are consistent with physiological cardiac hypertrophy. Spleens and kidneys were also smaller, although histologically normal, inMstn−/−mice. These data together suggest that attenuating myostatin could potentially prevent or possibly treat pathological conditions that develop with age. Additional studies are nevertheless needed to definitively assess potential risks to cardiac function. |
| Databáze: | OpenAIRE |
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