Klotho as a regulator of oxidative stress and senescence
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Makoto Kuro-o
Abstract
The klotho gene functions as an aging-suppressor gene that extends life span when overexpressed and accelerates aging-like phenotypes when disrupted in mice. The klotho gene encodes a single-pass transmembrane protein that binds to multiple fibroblast growth factor (FGF) receptors and functions as a co-receptor for FGF23, a bone-derived hormone that suppresses phosphate reabsorption and vitamin D biosynthesis in the kidney. In addition, the extracellular domain of Klotho protein is shed and secreted, potentially functioning as a humoral factor. The secreted Klotho protein can regulate multiple growth factor signaling pathways, including insulin/IGF-1 and Wnt, and the activity of multiple ion channels. Klotho protein also protects cells and tissues from oxidative stress, yet the precise mechanism underlying these activities remains to be determined. Thus, understanding of Klotho protein function is expected to provide new insights into the molecular basis for aging, phosphate/vitamin D metabolism, cancer and stem cell biology.
©2008 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Highlight: Oxidative Stress and Senescence
- Regulation of proteasome-mediated protein degradation during oxidative stress and aging
- Cellular responses to reactive oxygen species-induced DNA damage and aging
- Sirt1 protects the heart from aging and stress
- Klotho as a regulator of oxidative stress and senescence
- Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence
- Potential biomarkers of ageing
- Increased molecular damage and heterogeneity as the basis of aging
- Modulation of longevity-associated genes by estrogens or phytoestrogens
- FoxO transcription factors in oxidative stress response and ageing – a new fork on the way to longevity?
- Studies on the expression of 6S RNA from E. coli: involvement of regulators important for stress and growth adaptation
- New biological activity against phospholipase A2 by Turmerin, a protein from Curcuma longa L.
- Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs
- Kinetic properties of cathepsin D and BACE 1 indicate the need to search for additional β-secretase candidate(s)
Artikel in diesem Heft
- Highlight: Oxidative Stress and Senescence
- Regulation of proteasome-mediated protein degradation during oxidative stress and aging
- Cellular responses to reactive oxygen species-induced DNA damage and aging
- Sirt1 protects the heart from aging and stress
- Klotho as a regulator of oxidative stress and senescence
- Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence
- Potential biomarkers of ageing
- Increased molecular damage and heterogeneity as the basis of aging
- Modulation of longevity-associated genes by estrogens or phytoestrogens
- FoxO transcription factors in oxidative stress response and ageing – a new fork on the way to longevity?
- Studies on the expression of 6S RNA from E. coli: involvement of regulators important for stress and growth adaptation
- New biological activity against phospholipase A2 by Turmerin, a protein from Curcuma longa L.
- Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs
- Kinetic properties of cathepsin D and BACE 1 indicate the need to search for additional β-secretase candidate(s)
