Journal Article

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

Chia-Yu Wu, Yi-Fan Chen, Chih-Hao Wang, Cheng-Heng Kao, Hui-Wen Zhuang, Chih-Cheng Chen, Liang-Kung Chen, Ralph Kirby, Yau-Huei Wei, Shih-Feng Tsai and Ting-Fen Tsai

in Human Molecular Genetics

Volume 21, issue 18, pages 3956-3968
Published in print September 2012 | ISSN: 0964-6906
Published online June 2012 | e-ISSN: 1460-2083 | DOI:
A persistent level of Cisd2 extends healthy lifespan and delays aging in mice

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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 Article.  7403 words.  Illustrated.

Subjects: Genetics and Genomics

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