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
Year: 2012
Journal: Human molecular genetics
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.
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Created on Nov. 6, 2012, 10:57 a.m.
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Integrated: False

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Species: House mouse

Experiments: 0
Interventions:
  • Cisd2 overexpression

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