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, Ting Fen Tsai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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.

Original languageEnglish
Article numberdds210
Pages (from-to)3956-3968
Number of pages13
JournalHuman Molecular Genetics
Issue number18
StatePublished - Sep 2012


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