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

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.

Wu, Chia-Yu
Chen, Yi-Fan
Wang, Chih-Hao
Kao, Cheng-Heng
Zhuang, Hui-Wen
Chen, Chih-Cheng
Chen, Liang-Kung
Kirby, Ralph
Wei, Yau-Huei
Tsai, Shih-Feng
Tsai, Ting-Fen
Item Type: 
Journal Article
Publication Title: 
Human Molecular Genetics
Journal Abbreviation: 
Hum. Mol. Genet.
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 22661501

Turabian/Chicago Citation

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. 9/15/2012. "A persistent level of Cisd2 extends healthy lifespan and delays aging in mice." Human Molecular Genetics 21: 18: 3956-3968. 10.1093/hmg/dds210.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/hmg/dds210 | issn = 1460-2083 | volume = 21 | pages = 3956-3968 | last = Wu | first = Chia-Yu | coauthors = Chen, Yi-Fan, Wang, Chih-Hao, Kao, Cheng-Heng, Zhuang, Hui-Wen, Chen, Chih-Cheng, Chen, Liang-Kung, Kirby, Ralph, Wei, Yau-Huei, Tsai, Shih-Feng, Tsai, Ting-Fen | title = A persistent level of Cisd2 extends healthy lifespan and delays aging in mice | journal = Human Molecular Genetics | date = 9/15/2012 | pmid = | pmc = }} </ref>