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Augmented Wnt signaling in a mammalian model of accelerated aging.
- Source :
-
Science (New York, N.Y.) [Science] 2007 Aug 10; Vol. 317 (5839), pp. 803-6. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Apoptosis
Bone Density
Bone and Bones metabolism
Cell Count
Cell Line
Cell Shape
Glucuronidase chemistry
Glucuronidase genetics
Humans
Klotho Proteins
Mice
Mice, Transgenic
Protein Structure, Tertiary
Stem Cells cytology
Wnt Proteins antagonists & inhibitors
Wnt1 Protein metabolism
Wnt3 Protein
Aging physiology
Cellular Senescence physiology
Glucuronidase metabolism
Signal Transduction
Stem Cells physiology
Wnt Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 317
- Issue :
- 5839
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 17690294
- Full Text :
- https://doi.org/10.1126/science.1143578