Publication Date:
2007-08-11
Description:
The contribution of stem and progenitor cell dysfunction and depletion in normal aging remains incompletely understood. We explored this concept in the Klotho mouse model of accelerated aging. Analysis of various tissues and organs from young Klotho mice revealed a decrease in stem cell number and an increase in progenitor cell senescence. Because klotho is a secreted protein, we postulated that klotho might interact with other soluble mediators of stem cells. We found that klotho bound to various Wnt family members. In a cell culture model, the Wnt-klotho interaction resulted in the suppression of Wnt biological activity. Tissues and organs from klotho-deficient animals showed evidence of increased Wnt signaling, and ectopic expression of klotho antagonized the activity of endogenous and exogenous Wnt. Both in vitro and in vivo, continuous Wnt exposure triggered accelerated cellular senescence. Thus, klotho appears to be a secreted Wnt antagonist and Wnt proteins have an unexpected role in mammalian aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Hongjun -- Fergusson, Maria M -- Castilho, Rogerio M -- Liu, Jie -- Cao, Liu -- Chen, Jichun -- Malide, Daniela -- Rovira, Ilsa I -- Schimel, Daniel -- Kuo, Calvin J -- Gutkind, J Silvio -- Hwang, Paul M -- Finkel, Toren -- 1 R01 DK069989-01/DK/NIDDK NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 10;317(5839):803-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17690294" target="_blank"〉PubMed〈/a〉
Keywords:
Aging/*physiology
;
Animals
;
Apoptosis
;
Bone Density
;
Bone and Bones/metabolism
;
Cell Aging/*physiology
;
Cell Count
;
Cell Line
;
Cell Shape
;
Glucuronidase/chemistry/genetics/*metabolism
;
Humans
;
Mice
;
Mice, Transgenic
;
Protein Structure, Tertiary
;
*Signal Transduction
;
Stem Cells/cytology/*physiology
;
Wnt Proteins/antagonists & inhibitors/*metabolism
;
Wnt1 Protein/metabolism
;
Wnt3 Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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