ArticleAging cell2021
Cisd2 slows down liver aging and attenuates age-related metabolic dysfunction in male mice.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- A probioticGut microbes · 2026Article
- Cyclin D1 regulates the hepatic response to feeding: Evidence for non-cell cycle roles in the liver.bioRxiv : the preprint server for biology · 2026Article
- A machine learning-derived biological age model for liver grafts provides a superior assessment of aging compared to chronological age in transplantation.Scientific reports · 2026Article
- CISD2 ensures adequate ER-mitochondrial coupling, critically supporting mitochondrial function in neurons.Acta neuropathologica communications · 2025Article
- Lipid Metabolism-Signaling Crosstalk in Metabolic Disease and Aging: Mechanisms and Therapeutic Targets.Nutrients · 2025Review
- Accelerated Biological Aging, Genetic Susceptibility, and Non-Alcoholic Fatty Liver Disease: Two Prospective Cohort Studies.Nutrients · 2025Article
- Article
- CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury.Communications biology · 2024Article
- A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.Life medicine · 2024Article
- Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice.Journal of biomedical science · 2024Article
- Inhibition of ferroptosis by POLE2 in gastric cancer cells involves the activation of NRF2/GPX4 pathway.Journal of cellular and molecular medicine · 2024Article
- Article
- CISD2 transcriptional activated by transcription factor E2F7 promotes the malignant progression of cervical cancer.Journal of molecular histology · 2023Article
- The Roles of Lipid Metabolism in the Pathogenesis of Chronic Diseases in the Elderly.Nutrients · 2023Review
- A TNature aging · 2023Article
- Rejuvenation: Turning Back Time by Enhancing CISD2.International journal of molecular sciences · 2022Review
- Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice.Journal of biomedical science · 2022Article
- Dysregulated CaCells · 2022Review
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver plays a pivotal role in mammalian aging. However, the mechanisms underlying liver aging remain unclear. Cisd2 is a pro-longevity gene in mice. Cisd2 mediates lifespan and healthspan via regulation of calcium homeostasis and mitochondrial functioning. Intriguingly, the protein level of Cisd2 is significantly decreased by about 50% in the livers of old male mice. This down-regulation of Cisd2 may result in the aging liver exhibiting non-alcoholic fatty liver disease (NAFLD) phenotype. Here, we use Cisd2 transgenic mice to investigate whether maintaining Cisd2 protein at a persistently high level is able to slow down liver aging. Our study identifies four major discoveries. Firstly, that Cisd2 expression attenuates age-related dysregulation of lipid metabolism and other pathological abnormalities. Secondly, revealed by RNA sequencing analysis, the livers of old male mice undergo extensive transcriptomic alterations, and these are associated with steatosis, hepatitis, fibrosis, and xenobiotic detoxification. Intriguingly, a youthful transcriptomic profile, like that of young 3-month-old mice, was found in old Cisd2 transgenic male mice at 26 months old. Thirdly, Cisd2 suppresses the age-associated dysregulation of various transcription regulators (Nrf2, IL-6, and Hnf4a), which keeps the transcriptional network in a normal pattern. Finally, a high level of Cisd2 protein protects the liver from oxidative stress, and this is associated with a reduction in mitochondrial DNA deletions. These findings demonstrate that Cisd2 is a promising target for the development of therapeutic agents that, by bringing about an effective enhancement of Cisd2 expression, will slow down liver aging.
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Registered trials
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