| Title: | Targeting Longevity Gene SLC13A5: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis |
| Journal: | Metabolites |
| Published: | 6 Dec 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38132868/ |
| DOI: | https://doi.org/10.3390/metabo13121186 |
| URL: | https://www.mdpi.com/2218-1989/13/12/1186/pdf?version=1701860118 |
Publication 9218
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Reduced expression of the plasma membrane citrate transporter SLC13A5, also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and metabolic diseases. Citrate, a vital component of the tricarboxylic acid cycle, constitutes 1-5% of bone weight, binding to mineral apatite surfaces. Our previous research highlighted osteoblasts' specialized metabolic pathway facilitated by SLC13A5 regulating citrate uptake, production, and deposition within bones. Disrupting this pathway impairs bone mineralization in young mice. New Mendelian randomization analysis using UK Biobank data indicated that SNPs linked to reduced SLC13A5 function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific Slc13a5 knockout mice (Slc13a5cKO) showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced SLC13A5 function. These findings suggest reduced SLC13A5 function could attenuate age-related bone fragility, advocating for SLC13A5 inhibition as a potential osteoporosis treatment.</p>
7 Authors
- Grit Zahn
- Hannes A. Baukmann
- Jasmine Wu
- Jens Jordan
- Andreas L. Birkenfeld
- Naomi Dirckx
- Marco F. Schmidt
1 Application
| Application ID | Title |
|---|---|
| 36226 | Validation and improvement of our Machine Learning approach to analyze interactions in your genotyping/imputation data for better Familial Hypercholesterolemia diagnostics |
Enabling scientific discoveries that improve human health