國家衛生研究院 NHRI:Item 3990099045/14397
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    题名: Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice
    作者: Yeh, CH;Shen, ZQ;Wang, TW;Kao, CH;Teng, YC;Yeh, TK;Lu, CK;Tsai, TF
    贡献者: Institute of Molecular and Genomic Medicine;Institute of Biotechnology and Pharmaceutical Research
    摘要: Background The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an effective way of delaying aging. Methods Hesperetin was identified as a promising Cisd2 activator by herb compound library screening. Hesperetin has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used to investigate the effect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural defects and functional decline. Tissue-specific Cisd2 knockout mice were used to study the Cisd2-dependent anti-aging effects of hesperetin. RNA sequencing was used to explore the biological effects of hesperetin on aging. Results Three discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregulation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during old age. Conclusions Our findings indicate that a Cisd2 activator, hesperetin, represents a promising and broadly effective translational approach to slowing down aging and promoting longevity via the activation of Cisd2.
    日期: 2022-07-24
    關聯: Journal of Biomedical Science. 2022 Jul 24;29:Article number 53.
    Link to: http://dx.doi.org/10.1186/s12929-022-00838-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000829264600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85134638819
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