title: The aging myostatin null phenotype: reduced adiposity, cardiac hypertrophy, enhanced cardiac stress response, and sexual dimorphism.
abstract: 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) and Mstn-/- mice, lean fat-free mass and skeletal muscles composed of predominantly type I, II, and mixed fibers were significantly heavier in Mstn-/- 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 in Mstn-/- 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, in Mstn-/- 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.
authors.affiliation: School of Molecular Biosciences, Department of Veterinary Microbiology and Pathology, 124 ASLB, Washington Center for Muscle Biology, Washington State University, Pullman, Washington 99164, USA.
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Jackson
authors.forename: Dung
authors.initials: D
authors.lastname: Luong
authors.forename: Dor Dor
authors.initials: DD
authors.lastname: Vang
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Garikipati
authors.forename: James B
authors.initials: JB
authors.lastname: Stanton
authors.forename: O Lynne
authors.initials: OL
authors.lastname: Nelson
authors.forename: Buel D
authors.initials: BD
authors.lastname: Rodgers
mesh_terms: D002001:Adipose Tissue, Brown / Q000254:growth & development / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000375:Aging; D000818:Animals; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000235:genetics / Q000502:physiology*; D009929:Organ Size; D010641:Phenotype; D012044:Regression Analysis; D012737:Sex Factors; D013154:Spleen / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D002316:Cardiotonic Agents; D055435:Myostatin; D007545:Isoproterenol