title: Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice.
abstract: Mice deficient in pregnancy-associated plasma protein-A (PAPP-A) have extended lifespan associated with decreased incidence and severity of degenerative diseases of age, such as cardiomyopathy and nephropathy. In this study, the effect of PAPP-A deficiency on aging skeletal muscle was investigated. Whole-genome expression profiling was performed on soleus muscles from 18-month-old wild-type (WT) and PAPP-A knock-out (KO) mice of the same sex and from the same litter ('womb-mates') to identify potential mechanisms of skeletal muscle aging and its retardation in PAPP-A deficiency. Top genes regulated in PAPP-A KO compared to WT muscle were associated with increased muscle function, increased metabolism, in particular lipid metabolism, and decreased stress. Fiber cross-sectional area was significantly increased in solei from PAPP-A KO mice. In vitro contractility experiments indicated increased specific force and decreased fatigue in solei from PAPP-A KO mice. Intrinsic mitochondrial oxidative capacity was significantly increased in skeletal muscle of aged PAPP-A KO compared to WT mice. Moreover, 18-month-old PAPP-A KO mice exhibited significantly enhanced endurance running on a treadmill. Thus, PAPP-A deficiency in mice is associated with indices of healthy skeletal muscle function with age.
authors.affiliation: Division of Endocrinology, Metabolism, and Nutrition, Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: Conover.Cheryl@mayo.edu.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
authors.affiliation: Division of Endocrinology, Metabolism, and Nutrition, Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: Bale.Laurie@mayo.edu.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Bale
authors.affiliation: Division of Endocrinology, Metabolism, and Nutrition, Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: Nair@mayo.edu.
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D005080:Exercise Test; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D053208:Kaplan-Meier Estimate; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010641:Phenotype; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D011266:Pregnancy-Associated Plasma Protein-A
keywords: Mitochondria; Pregnancy-associated plasma protein-A; Soleus