ReferenceID 2040
Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice
J Biomed Sci
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
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2040
- Evidence Id
- 18630
- Core Evidence Id
- 18630
- Source Reference Id
- 4100
- Herb2 Reference Id
- HBREF004897
- Subject Paper Key
- HBIN029190_35871686
- Pubmed Id
- 35871686
- Doi
- 10.1186/s12929-022-00838-7
- Paper Title
- Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice
- Paper 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.
- Journal
- J Biomed Sci
- Publish Year
- 2022
- Experiment Subject
- mouse; human
- Experiment Type
- Animal Experiment
- Phenotype Related
- Age-related Structural Defects
- Paper Title Cn
- Paper Title En
- Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice
- Bilingual Status
- semi_complete