Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models
Ver/ Abrir
Impacto
Scholar |
Otros documentos de la autoría: Costa-Machado, Luis Filipe; García-Domínguez, Esther; McIntyre, Rebecca L.; Lopez Aceituno, Jose Luis; Ballesteros-González, Álvaro; Tapia-Gonzalez, Andrea; Fabregat-Safont, David; Eisenberg, Tobias; Gómez, Jesús; Plaza, Adrian; Sierra Ramírez, Arantzazu; Pérez, Manuel; Villanueva Bermejo, David; Fornari, Tiziana; Loza García, María Isabel; Herradón, Gonzalo; Hofer, Sebastian; Magnes, Christoph; Madeo, Frank; Duerr, Janet S.; Pozo, Oscar; Galindo, Máximo Ibo; del Pino, Isabel; Houtkooper, Riekelt H.; Megias, Diego; Viña, José; Gomez-Cabrera , Mari Carmen; Fernandez-Marcos, Pablo J.
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadatos
Título
Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical modelsAutoría
Fecha de publicación
2023Editor
Nature ResearchCita bibliográfica
Costa-Machado, L.F., Garcia-Dominguez, E., McIntyre, R.L. et al. Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models. Nat Commun 14, 2779 (2023). https://doi.org/10.1038/s41467-023-38410-yTipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://www.nature.com/articles/s41467-023-38410-yVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Reversible and sub-lethal stresses to the mitochondria elicit a program of
compensatory responses that ultimately improve mitochondrial function, a
conserved anti-aging mechanism termed mitohormesis. Here, we show ... [+]
Reversible and sub-lethal stresses to the mitochondria elicit a program of
compensatory responses that ultimately improve mitochondrial function, a
conserved anti-aging mechanism termed mitohormesis. Here, we show that
harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends
healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose
tissue and muscle, even though harmol crosses poorly the blood–brain barrier.
Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their
glucose tolerance, liver steatosis and insulin sensitivity after treatment with
harmol. Harmol or a combination of monoamine oxidase B and GABA-A
receptor modulators extend the lifespan of hermaphrodite Caenorhabditis
elegans or female Drosophila melanogaster. Finally, two-year-old male and
female mice treated with harmol exhibit delayed frailty onset with improved
glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis. [-]
Publicado en
Nature Communications | (2023) 14:2779Entidad financiadora
IMDEA Food Institute | Ramón Areces Foundation | AECC | Ministerio de Ciencia e Innovación | Fondo Europeo de Desarrollo Regional | Instituto de Salud Carlos III | Generalitat Valenciana | European Commision | Austrian Science Fund (FWF) | University of Graz | Austrian Federal Ministry of Education, Science and Research | Ministerio de Universidades
Código del proyecto o subvención
CIVP18A3891 | SIRTBIO, LABAE18008FERN | SAF2017-85766-R | PRPPID2020-114077RB-I00 | MICINN, RYC-2017-22335 | PTA2017-14689-I | CB16/10/ 00435 (CIBERFES) | PID2019-110906RB-I00/AEI/10.13039/ 501100011033 | FGCSIC/PSLINTERREG/FEDER | PROMETEO/2019/097 | info:eu-repo/grantAgreement/EC/H2020/825546 | RTI2018-100872-J-I00 | CIDENGENT/2019/044 | PROMETEU/2018/135 | FPU18/05350 | SFB-LIPOTOX F3007 & F3012 | W1226 | P29203 | P29262 | P27893 | P31727 | BMWFW-80.109/0001-WF/V/3b/2015 | MGS/2021/15
Derechos de acceso
info:eu-repo/semantics/openAccess
Aparece en las colecciones
- IUPA_Articles [307]
- QFA_Articles [817]