Premature aging‐like phenotype in <i>fibroblast growth factor 23</i> null mice is a vitamin D‐mediated process

Abstract

ABSTRACT Fibroblast growth factor 23 null mice ( Fgf‐23 −/− ) have a short lifespan and show numerous biochemical and morphological features consistent with premature aging‐like phenotypes, including kyphosis, severe muscle wasting, hypogonadism, osteopenia, emphysema, uncoordinated movement, T cell dysregulation, and atrophy of the intestinal villi, skin, thymus, and spleen. Furthermore, increased vitamin D activities in homozygous mutants are associated with severe atherosclerosis and widespread soft tissue calcifications; ablation of vitamin D activity from Fgf‐23 −/− mice, by genetically deleting the 1 α (OH)ase gene, eliminates atherosclerosis and ectopic calcifications and significantly rescues premature aging‐like features of Fgf‐23 −/− mice, resulting in prolonged survival of Fgf‐23 −/− /1α(OH)ase −/− double mutants. Our results indicate a novel role of Fgf‐23 in developing premature aging‐like features through regulating vitamin D homeostasis. Finally, our data support a new model of interactions among Fgf‐23, vitamin D, and klotho , a gene described as being associated with premature aging process.

Keywords

Affiliated Institutions

• Shriners Hospitals for Children - Canada CA
• Harvard University US
• Nagasaki University JP

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