Amigo 2016 Aging Cell

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Amigo I, Menezes-Filho SL, Luévano-Martínez LA, Chausse B, Kowaltowski AJ (2016) Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity. Aging Cell 16:73-81.

» PMID: 27619151 Open Access

Amigo I, Menezes-Filho SL, Luevano-Martinez LA, Chausse B, Kowaltowski AJ (2016) Aging Cell

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.

© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Keywords: Aging, Brain, Calcium, Caloric restriction, Mitochondria

O2k-Network Lab: BR Sao Paulo Kowaltowski AJ


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Nervous system  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase  Regulation: Calcium  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S  HRR: Oxygraph-2k 

2016-11