Caloric Restriction Increases Brain Mitochondrial Calcium Retention Capacity and Protects Against Excitotoxicity

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2016 Sep 14

PMID 27619151

Citations 33

Authors

Ignacio Amigo

Sergio Luiz Menezes-Filho

Luis Alberto Luevano-Martinez

Bruno Chausse

Alicia J Kowaltowski

Affiliations

Soon will be listed here.

Abstract

Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic insults in vitro and in vivo in a manner associated with significant changes in mitochondrial function. CR increases electron transport chain activity, enhances antioxidant defenses, and favors mitochondrial calcium retention capacity in the brain. These changes are accompanied by a decrease in cyclophilin D activity and acetylation and an increase in Sirt3 expression. This suggests that Sirt3-mediated deacetylation and inhibition of cyclophilin D in CR promote the inhibition of mitochondrial permeability transition, resulting in enhanced mitochondrial calcium retention. Altogether, our results indicate that enhanced mitochondrial calcium retention capacity underlies the beneficial effects of CR against excitotoxic conditions. This protection may explain the many beneficial effects of CR in the aging brain.

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