期刊
AGING CELL
卷 16, 期 1, 页码 73-81出版社
WILEY-BLACKWELL
DOI: 10.1111/acel.12527
关键词
aging; brain; calcium; caloric restriction; mitochondria
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2010/51906-1]
- Centro de Pesquisa, Inovacao e Difusao de Processos Redox em Biomedicina [13/ 07937-8]
- Nucleo de Pesquisa em Processos Redox em Biomedicina (NAP-Redoxoma)
- Instituto Nacional de Ciencia e Tecnologia de Processos Redox em Biomedicina (INCT Redoxoma)
- Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [153560/2011-8, 302898/2013-1]
- FAPESP [2012/51288-1]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据