RT info:eu-repo/semantics/article
T1 Mechanism of the lifespan extension induced by submaximal SERCA inhibition in C. elegans
A1 García Casas, Paloma
A1 Álvarez Illera, María Pilar
A1 Fonteriz García, Rosalba Inés
A1 Montero Zoccola, María Teresa
A1 Álvarez Martín, Javier
K1 C. elegans, SERCA, Thapsigargin, Lifespan, Endoplasmic reticulum, Mitochondria, AMP kinase, TOR
AB We have reported recently that submaximal inhibition of the Sarco Endoplasmic Reticulum Ca2+ ATPase(SERCA) produces an increase in the lifespan of C. elegans worms. We have explored here the mechanism of this increased survival by studying the effect of SERCA inhibition in several mutants of signaling pathways related to longevity. Our data show that the mechanism of the effect is unrelated with the insulin signaling pathway or the sirtuin activity, because SERCA inhibitors increased lifespan similarly in mutants of these pathways. However, the effect required functional mitochondria and both the AMP kinase and TOR pathways, as the SERCA inhibitors were ineffective in the corresponding mutants. The same effects were obtained after reducing SERCA expression with submaximal RNAi treatment. The SERCA inhibitors did not induce ER-stress at the concentrations used, and their effect was not modified by inactivation of the OP50 bacterial food. Altogether, our data suggest that the effect may be due to a reduced ER-mitochondria Ca2+ transfer acting via AMPK activation and mTOR inhibition to promote survival.
PB Elsevier
SN 0047-6374
YR 2021
FD 2021
LK https://uvadoc.uva.es/handle/10324/66248
UL https://uvadoc.uva.es/handle/10324/66248
LA eng
NO Mechanisms of Ageing and Development, Marzo 2021, 196, 111474
NO Producción Científica
DS UVaDOC
RD 22-nov-2024