Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice.
The essential role of low levels of vitamin D during aging is well documented. However, possible effects of high levels of vitamin D on the aging process are not yet clear. Recent in vivo genetic-manipulation studies have shown increased serum level of vitamin D and altered mineral-ion homeostasis in mice that lack either fibroblast growth factor 23 (Fgf23) or klotho (Kl) genes. These mice develop identical phenotypes consistent with premature aging. Elimination or reduction of vitamin-D activity from Fgf23 and Kl mutant mice, either by dietary restriction or genetic manipulation could rescue premature aging-like features and ectopic calcifications, resulting in prolonged survival of both mutants. Such in vivo experimental studies indicated that excessive vitamin-D activity and altered mineral-ion homeostasis could accelerate the aging process.
Razzaque
Mohammed S
MS
Department of Developmental Biology, Harvard School of Dental Medicine, Research and Educational Building, 190 Longwood Avenue, Boston, MA 02115, USA. mrazzaque@hms.harvard.edu
Lanske
Beate
B
D000375:Aging / Q000502:physiology; D019588:Aging, Premature / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D005966:Glucuronidase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D010710:Phosphates / Q000378:metabolism; D015398:Signal Transduction; D014807:Vitamin D / Q000502:physiology*
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium