PuSH - Publication Server of Helmholtz Zentrum München: Targeting longevity gene <em>SLC13A5</em>: A novel approach to prevent age-related bone fragility and osteoporosis.

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Zahn, G.* ; Baukmann, H.A.* ; Wu, J.* ; Jordan, J.* ; Birkenfeld, A.L. ; Dirckx, N.* ; Schmidt, M.F.*

Targeting longevity gene SLC13A5: A novel approach to prevent age-related bone fragility and osteoporosis.

Metabolites 13:1186 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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 (Slc13a5^cKO) 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Mendelian Randomization ; Nact ; Slc13a5 ; Citrate ; Citrate Transporter ; Drug Development ; Mindy ; Osteoporosis; Plasma Citrate; Mouse Model; Nact; Transporter; Association; Mutations; Insulin

ISSN (print) / ISBN 2218-1989

e-ISSN 2218-1989

Journal Metabolites

Quellenangaben Volume: 13, Issue: 12, Article Number: 1186

Publisher MDPI

Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)

Grants Eternygen GmbH