A persistent level of Cisd2 extends healthy lifespan and delays aging in mice.

Authors: Wu CY; Chen YF; Wang CH; Kao CH; Zhuang HW; Chen CC; Chen LK; Kirby R; Wei YH; Tsai SF; Tsai TF

Abstract: The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, the CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging in mice. Additionally, an age-dependent decrease in Cisd2 expression has been detected during normal aging. In this study, we demonstrate that a persistent level of Cisd2 achieved by transgenic expression in mice extends their median and maximum lifespan without any apparent deleterious side effects. Cisd2 also ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. These results suggest that Cisd2 is a fundamentally important regulator of lifespan and provide an experimental basis for exploring the candidacy of CISD2 in human longevity.

Journal: Human molecular genetics
Volume: 21
Issue: 18
Pages: 3956-68
Date: June 5, 2012
PMID: 22661501
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Wu CY, Chen YF, Wang CH, Kao CH, Zhuang HW, Chen CC, Chen LK, Kirby R, Wei YH, Tsai SF, Tsai TF (2012) A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Human molecular genetics 21: 3956-68.

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