Abstract
Mice carrying a loss-of-function mutation in the klotho gene (KL -/- mice) develop ageing-like symptoms around 4 weeks after birth and suffer from multiple age-related disorders observed in humans, including osteoporosis, arteriosclerosis, and pulmonary emphysema. The klotho gene encodes a single-pass transmembrane protein that may function in signaling pathways that suppress ageing. To investigate the ability of Klotho to regulate the development of ageing-related disorders, we established an inducible Klotho expression system using KL-/- mice carrying an exogenous klotho gene fused to the mouse metallothionein-I promoter, in which Klotho expression was dependent on zinc water feeding. We demonstrate that many advanced ageing-like KL-/- phenotypes were restored to normal whenever Klotho expression was induced. Conversely, decreasing Klotho expression in these rescued KL -/- mice induced several ageing-like KL-/- phenotypes. Our data indicate that Klotho may be effective in the treatment of multiple age-related disorders and is essential for maintaining animals free of these disorders.
Original language | English (US) |
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Pages (from-to) | 1274-1283 |
Number of pages | 10 |
Journal | Mechanisms of Ageing and Development |
Volume | 126 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2005 |
Keywords
- Ageing
- Klotho
- Transgenic mice
ASJC Scopus subject areas
- Aging
- Developmental Biology