Advances in endocrinology of aging research, 2005-2006.
The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. Four advances were chosen and briefly described. First, exploration of the early steps in the generation of the internal steroidal hormonal signal involved in lifespan extension via the insulin/IGF-like signaling pathway in the nematode by two research groups revealed that the product of cholestanoic acid derivatives metabolized by a cytochrome P-450-like protein activates a protein with homology to the mammalian nuclear receptor superfamily, a process strikingly similar to the steroid hormone signaling pathway documented in mammalian systems. Second is the discovery that sirtuins, proteins that regulate lifespan in model organisms, enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting the potential to regulate mammalian lifespan through regulation of the insulin signaling pathway. Third, the newly discovered hormone klotho, which also plays a role in regulating lifespan, in this case in mice, is reported to not only negatively affect insulin sensitivity but, perhaps more importantly, significantly affects calcium and phosphate metabolism as a required cofactor of Fgf-23 signaling. Finally the gonadotropin FSH is shown to directly affect bone density in mice separate from any direct effect of estrogen, suggesting that reproductive hormones other than estrogen can directly impact menopause-associated pathophysiology in non-reproductive tissues.
Bellino
Francis L
FL
Biology of Aging Program, National Institute on Aging Bethesda, MD 20891, USA. bellinof@mail.nih.gov
D000375:Aging / Q000502:physiology*; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005947:Glucose / Q000502:physiology; D005966:Glucuronidase / Q000502:physiology; D006065:Gonadotropins, Pituitary / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D000090265:Klotho Proteins; D008055:Lipids / Q000502:physiology; D008136:Longevity / Q000502:physiology; D008297:Male; D008593:Menopause / Q000502:physiology; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D006065:Gonadotropins, Pituitary; D007328:Insulin; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D013002:Somatomedins; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D005947:Glucose