Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction (Cell, 2010, 143:802-812)

報告日期: 2011/04/12
報告時間: 15:10/16:00
報告學生: 蘇柏全 (英文報告)
講評老師: 陳昌熙

Full Text:

Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction
Shinichi Someya,Wei Yu,William C. Hallows,Jinze Xu,James M. Vann,Christiaan Leeuwenburgh,Masaru Tanokura,John M. Denu,and Tomas A. Prolla
Cell 143, 802–812, 2010
Commentator: Chang-Shi Chen Ph.D.
Speaker: Bor Chyuan Su
Age-related hearing loss (AHL) is very common sensory disorder in the elderly1. The hallmarks of AHL are loss of spiral ganglion and sensory hair cells in the cochlea of the inner ear. Previous study indicated that caloric restriction (CR) prevent AHL through reduction of oxidative damage and/or by enhancing cellular antioxidant defenses to oxidative stress1, 2. However, the molecular mechanism of CR-mediated AHL prevention is still unclear. This report provides a link between the mitochondrial deacetylase, Sirt3, one of the members of the sirtulin family and CR-induced protective effect during aging. The level of Sirt3 is upregulated during CR, and activates mitochondrial isocitrate dehydrogenase 2 (Idh2). Activated Idh2 increases NADPH levels and ratio of reduced form of glutathione (GSH) to oxidized form of glutathione (GSSG). Furthermore, overexpression of Sirt3 or Idh2 prevents oxidative stress-induced cell death. Collectively, this report indicates that Sirt3 plays an essential role in CR-mediated prevention of age-related hearing loss in mice.