Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice
Abstract 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 Ci...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-022-00838-7 |
| _version_ | 1818493354336321536 |
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| author | Chi-Hsiao Yeh Zhao-Qing Shen Tai-Wen Wang Cheng-Heng Kao Yuan-Chi Teng Teng-Kuang Yeh Chung-Kuang Lu Ting-Fen Tsai |
| author_facet | Chi-Hsiao Yeh Zhao-Qing Shen Tai-Wen Wang Cheng-Heng Kao Yuan-Chi Teng Teng-Kuang Yeh Chung-Kuang Lu Ting-Fen Tsai |
| author_sort | Chi-Hsiao Yeh |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T17:54:08Z |
| format | Article |
| id | doaj.art-d11df834c11b41a3ac3d234147818e8f |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-10T17:54:08Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-d11df834c11b41a3ac3d234147818e8f2022-12-22T01:39:00ZengBMCJournal of Biomedical Science1423-01272022-07-0129112110.1186/s12929-022-00838-7Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged miceChi-Hsiao Yeh0Zhao-Qing Shen1Tai-Wen Wang2Cheng-Heng Kao3Yuan-Chi Teng4Teng-Kuang Yeh5Chung-Kuang Lu6Ting-Fen Tsai7Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial HospitalDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung UniversityCenter of General Education, Chang Gung UniversityDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung UniversityInstitute of Biotechnology and Pharmaceutical Research, National Health Research InstitutesDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung UniversityAbstract 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.https://doi.org/10.1186/s12929-022-00838-7LongevityNatural agingCisd2Hesperetin |
| spellingShingle | Chi-Hsiao Yeh Zhao-Qing Shen Tai-Wen Wang Cheng-Heng Kao Yuan-Chi Teng Teng-Kuang Yeh Chung-Kuang Lu Ting-Fen Tsai Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice Journal of Biomedical Science Longevity Natural aging Cisd2 Hesperetin |
| title | Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice |
| title_full | Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice |
| title_fullStr | Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice |
| title_full_unstemmed | Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice |
| title_short | Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice |
| title_sort | hesperetin promotes longevity and delays aging via activation of cisd2 in naturally aged mice |
| topic | Longevity Natural aging Cisd2 Hesperetin |
| url | https://doi.org/10.1186/s12929-022-00838-7 |
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