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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)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Metabolites
Quellenangaben Band: 13, Heft: 12, Seiten: , Artikelnummer: 1186 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Eternygen GmbH