Quetiapine Shortens the Lifespan of Caenorhabditis elegans through DOP-2, DAF-2 and RSKS-1.
Int J Mol Sci
; 23(21)2022 Oct 26.
Article
en En
| MEDLINE
| ID: mdl-36361717
Recent studies implicate a key role of dopamine signaling in lifespan regulation. Our previous study found that quetiapine, an atypical antipsychotic drug that has antagonistic activity on dopamine D2-like receptors (D2Rs), shortened the lifespan of Caenorhabditis elegans (C. elegans). However, the detailed mechanism of this effect was not clear. In the present study, we evaluate the effect of quetiapine on aging and explore its underlying molecular mechanism. The results show that quetiapine shortened healthspan in C. elegans. The lifespan-shortening effect is dependent on DOP-2, a D2R expressed in worms. Quetiapine shortens lifespan through the C. elegans insulin and IGF-1 receptor DAF-2, but not the downstream Akt pathway. Quetiapine-induced lifespan reduction is dependent on RSKS-1, a key protein kinase that functions in mTOR signaling. In addition, the quetiapine effect is also related to mitochondrial function. These findings further support the key role of dopamine signaling in lifespan regulation and promote our insight into the mechanism of action of antipsychotic drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Caenorhabditis elegans
/
Proteínas de Caenorhabditis elegans
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Suiza