國家衛生研究院 NHRI:Item 3990099045/8219
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    题名: Cisd2 mediates lifespan: Is there an interconnection among Ca2+ homeostasis, autophagy, and lifespan?
    作者: Wang, CH;Kao, CH;Chen, YF;Wei, YH;Tsai, TF
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: CISD2, an evolutionarily conserved novel gene, plays a crucial role in lifespan control and human disease. Mutations in human CISD2 cause type 2 Wolfram syndrome, a rare neurodegenerative and metabolic disorder associated with a shortened lifespan. Significantly, the CISD2 gene is located within a region on human chromosome 4q where a genetic component for human longevity has been mapped through a comparative genome analysis of centenarian siblings. We created Cisd2 knockout (loss-of-function) and transgenic (gain-of-function) mice to study the role of Cisd2 in development and pathophysiology, and demonstrated that Cisd2 expression affects lifespan in mammals. In the Cisd2 knockout mice, Cisd2 deficiency shortens lifespan and drives a panel of premature aging phenotypes. Additionally, an age-dependent decrease of Cisd2 expression has been detected during normal aging in mice. Interestingly, in the Cisd2 transgenic mice, we demonstrated that a persistent level of Cisd2 expression over the different stages of life gives the mice a long-lived phenotype that is linked to an extension in healthy lifespan and a delay in age-associated diseases. At the cellular level, Cisd2 deficiency leads to mitochondrial breakdown and dysfunction accompanied by cell death with autophagic features. Recent studies revealed that Cisd2 may function as an autophagy regulator involved in the Bcl-2 mediated regulation of autophagy. Furthermore, Cisd2 regulates Ca2+ homeostasis and Ca2+ has been proposed to have an important regulatory role in autophagy. Finally, it remains to be elucidated if and how the regulation in Ca2+ homeostasis, autophagy and lifespan are interconnected at the molecular, cellular and organism levels.
    日期: 2014-09
    關聯: Free Radical Research. 2014 Sep;48(9):1109-1114.
    Link to: http://dx.doi.org/10.3109/10715762.2014.936431
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1071-5762&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000340456000014
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84906064938
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