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Title

Effect of Sarco-Endoplasmic Reticulum Ca2+-ATPase (SERCA) inhibition on C. elegans life span and pharynx Ca2+ signaling

AuthorsGarcía-Casas, Paloma; Alvarez-Illera, Pilar; Arias-del-Val, Jessica; Fonteriz, Rosalba I. ; Álvarez, Javier; Montero, Mayte
Issue Date2017
CitationVI Spanish Worm Meeting (2017)
AbstractThe nematode C. elegans is widely used for aging research and many specific gene mutations modify lifespan. Remarkably, many of the mutants with increased lifespan show slow physiological rates and delayed development, even though ATP levels may be normal. Several authors have proposed that increased lifespan may be achieved by decreasing somehow energy expenditure, the so-called reduced “rate of living”. To test this hypothesis we have studied the effects of altering intracellular Ca2+ signaling. Transient increases in cytosolic Ca2+ are the key signal for muscle contraction, neurotransmitter release, cell proliferation and many metabolic reactions. Moreover, Ca2+ entry into mitochondria activates respiration and ATP production. An important portion of the Ca2+ responsible for these actions comes from the endoplasmic reticulum (ER), where it is stored at high concentration by SERCA pumps. We therefore reasoned that reducing the amount of Ca2+ stored in the ER should slow metabolism and energy expenditure. We have studied here the effect of 2,5-BHQ, a reversible inhibitor of SERCA, on both C. elegans lifespan and pharynx Ca2+ signaling measured with a targeted fluorescent Ca2+ sensor. Our results show that, although high concentrations of the inhibitor are toxic and reduce lifespan, there is a range of concentrations that increase lifespan up to about 20% compared with the controls and with the inactive isomer 2,6-BHQ. Differential effects of both isomers on pharynx Ca2+ signaling are also described. Our results are consistent with the idea that reducing the rate of energy expenditure is able to increase lifespan.
DescriptionResumen del trabajo presentado al VI Spanish Worm Meeting, celebrado en Valencia del 9 al 10 de marzo de 2017.
URIhttp://hdl.handle.net/10261/163896
Appears in Collections:(IBGM) Comunicaciones congresos
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