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.
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Chia-Yu
CY
Wu
Yi-Fan
YF
Chen
Chih-Hao
CH
Wang
Cheng-Heng
CH
Kao
Hui-Wen
HW
Zhuang
Chih-Cheng
CC
Chen
Liang-Kung
LK
Chen
Ralph
R
Kirby
Yau-Huei
YH
Wei
Shih-Feng
SF
Tsai
Ting-Fen
TF
Tsai
D000818:Animals; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004579:Electron Transport / Q000235:genetics; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008017:Life Expectancy; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009132:Muscles / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000473:pathology; D009245:NADH Dehydrogenase / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010101:Oxygen Consumption; D055948:Sarcopenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D015595:Skin Aging / Q000235:genetics
D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C515811:Noxp70 protein, mouse; D009245:NADH Dehydrogenase; D005978:Glutathione