ArticleJournal of biomedical science2022
Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 58 citations in OpenAlex.
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- Body Mass Index and Facial Aging: Mendelian Randomization and Exploratory Target Prioritization.Clinical, cosmetic and investigational dermatology · 2026Article
- Prolonged Survival with Dieting for Improved Autophagy.Non-coding RNA · 2025Review
- Hesperidin and Hesperetin from Orange Peel Water Extract Protect against NaIOJournal of agricultural and food chemistry · 2025Article
- Hesperetin Alleviates Bleomycin-Induced Pulmonary Fibrosis by Modulating Cellular Senescence and Promoting Impaired Autophagy in a CISD2-Dependent Manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Metabolic Reprogramming Through Polyphenol Networks: A Systems Approach to Metabolic Inflammation and Insulin Resistance.Medical sciences (Basel, Switzerland) · 2025Review
- Cisd2 delays atrial aging via a modulation of calcium homeostasis that mitigates atrial myopathy.Cell communication and signaling : CCS · 2025Article
- Review
- The Antiaging Potential of Dietary Plant-Based Polyphenols: A Review on Their Role in Cellular Senescence Modulation.Nutrients · 2025Review
- Analyzing mechanisms of qing fei bao yuan decoction granules in treating COPD based on LC-MS, network pharmacology and in vivo methods.Journal of traditional and complementary medicine · 2025Article
- Efficacy of Naringenin against aging and degeneration of nucleus pulposus cells through IGFBP3 inhibition.Scientific reports · 2025Article
- Harnessing hesperidin for brain metabolism: epigenetic signatures, cellular homeostasis, synaptic function, and neuroprotection in age-related diseases and neurodegenerative diseases.Frontiers in nutrition · 2025Review
- Article
- Hesperetin Increases Lifespan and Antioxidant Ability Correlating with IIS, HSP, mtUPR, and JNK Pathways of Chronic Oxidative Stress inInternational journal of molecular sciences · 2024Article
- Article
- Insights into the Therapeutic Potential of Active Ingredients ofInternational journal of molecular sciences · 2024Article
- Deep Learning-Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP.Chinese medicine · 2024Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe 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.
methodsHesperetin 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.
resultsThree 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.
conclusionsOur 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.