Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis
Reduced expression of the plasma membrane citrate transporter <i>SLC13A5</i>, 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 w...
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MDPI AG
2023-12-01
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| Online Access: | https://www.mdpi.com/2218-1989/13/12/1186 |
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| author | Grit Zahn Hannes A. Baukmann Jasmine Wu Jens Jordan Andreas L. Birkenfeld Naomi Dirckx Marco F. Schmidt |
| author_facet | Grit Zahn Hannes A. Baukmann Jasmine Wu Jens Jordan Andreas L. Birkenfeld Naomi Dirckx Marco F. Schmidt |
| author_sort | Grit Zahn |
| collection | DOAJ |
| description | Reduced expression of the plasma membrane citrate transporter <i>SLC13A5</i>, 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 <i>SLC13A5</i> 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 <i>SLC13A5</i> function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific <i>Slc13a5</i> knockout mice (<i>Slc13a5<sup>cKO</sup></i>) showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced <i>SLC13A5</i> function. These findings suggest reduced <i>SLC13A5</i> function could attenuate age-related bone fragility, advocating for <i>SLC13A5</i> inhibition as a potential osteoporosis treatment. |
| first_indexed | 2024-03-08T20:32:30Z |
| format | Article |
| id | doaj.art-01fe8716f85649ccbdeaaf5fbe349067 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-08T20:32:30Z |
| publishDate | 2023-12-01 |
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| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-01fe8716f85649ccbdeaaf5fbe3490672023-12-22T14:24:27ZengMDPI AGMetabolites2218-19892023-12-011312118610.3390/metabo13121186Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and OsteoporosisGrit Zahn0Hannes A. Baukmann1Jasmine Wu2Jens Jordan3Andreas L. Birkenfeld4Naomi Dirckx5Marco F. Schmidt6Eternygen GmbH, Westhafenstrasse 1, 13353 Berlin, Germanybiotx.ai GmbH, Am Mühlenberg 11, 14476 Potsdam, GermanyDepartment of Orthopaedics, School of Medicine, University of Maryland-Baltimore, Baltimore, MD 21201, USAGerman Aerospace Center (DLR), Institute of Aerospace Medicine, 51147 Cologne, GermanyDepartment of Diabetology Endocrinology and Nephrology, Internal Medicine IV, University Hospital Tübingen, Eberhard Karls University Tübingen, 72074 Tübingen, GermanyDepartment of Orthopaedics, School of Medicine, University of Maryland-Baltimore, Baltimore, MD 21201, USAbiotx.ai GmbH, Am Mühlenberg 11, 14476 Potsdam, GermanyReduced expression of the plasma membrane citrate transporter <i>SLC13A5</i>, 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 <i>SLC13A5</i> 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 <i>SLC13A5</i> function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific <i>Slc13a5</i> knockout mice (<i>Slc13a5<sup>cKO</sup></i>) showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced <i>SLC13A5</i> function. These findings suggest reduced <i>SLC13A5</i> function could attenuate age-related bone fragility, advocating for <i>SLC13A5</i> inhibition as a potential osteoporosis treatment.https://www.mdpi.com/2218-1989/13/12/1186mINDY<i>SLC13A5</i>citratecitrate transporterNaCTosteoporosis |
| spellingShingle | Grit Zahn Hannes A. Baukmann Jasmine Wu Jens Jordan Andreas L. Birkenfeld Naomi Dirckx Marco F. Schmidt Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis Metabolites mINDY <i>SLC13A5</i> citrate citrate transporter NaCT osteoporosis |
| title | Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis |
| title_full | Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis |
| title_fullStr | Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis |
| title_full_unstemmed | Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis |
| title_short | Targeting Longevity Gene <i>SLC13A5</i>: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis |
| title_sort | targeting longevity gene i slc13a5 i a novel approach to prevent age related bone fragility and osteoporosis |
| topic | mINDY <i>SLC13A5</i> citrate citrate transporter NaCT osteoporosis |
| url | https://www.mdpi.com/2218-1989/13/12/1186 |
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