title: Circulating Concentrations of Growth Differentiation Factor 11 Are Heritable and Correlate With Life Span.
abstract: Growth differentiation factor 11 (GDF11) is member of the transforming growth factor β (TGF-β) superfamily of proteins. Circulating GDF11 concentrations appear to decline with age, and its depletion is associated with cardiac hypertrophy and other morbidities. Knowledge of GDF11 regulation is limited, and the effects of natural genetic variation on GDF11 levels are currently undefined. We tested whether genetic background determines serum GDF11 concentrations using two classical inbred mouse strains: C57BL/6J (B6) and BALB/cByJ (BALB). B6 mice exhibited significantly higher GDF11 levels than BALB mice, and these strain differences were consistent throughout the life span. Overall, interactions between age and genetic background determined GDF11 concentrations, which were unaffected by sex. We then surveyed a panel of 22 genetically diverse inbred mouse strains and discovered a sixfold range in GDF11 levels at middle age. We estimated that 74.52% of phenotypic variation in GDF11 levels was attributable to genetic background. We used the Mouse Phenome Database to screen for phenotypes that correlate with GDF11. Interestingly, GDF11 levels predicted median strain life spans. This study revealed high heritability of GDF11 levels. Furthermore, our correlative data suggest that GDF11 may serve as a novel predictor of mammalian life span.
authors.affiliation: Department of Foods and Nutrition and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Foods and Nutrition and.
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Foods and Nutrition and.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Harris
authors.affiliation: Department of Statistics, University of Georgia, Athens.
authors.forename: Jaxk
authors.initials: J
authors.lastname: Reeves
authors.affiliation: Department of Statistics, University of Georgia, Athens.
authors.forename: Xianyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Foods and Nutrition and rpazdro@uga.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Pazdro
mesh_terms: D000375:Aging / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055412:Growth Differentiation Factors / Q000097:blood* / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors
keywords: Anti-aging; Cardiovascular; Genetics; Hormones; Longevity.