Evidence map›Paper›PMID 42640396›Full record

ArticleBiogerontology2026

ODC1-associated astrocytic urea cycle dysregulation in age-related memory impairment.

Mengna Wu, Shengyao Zhang, Xi Zhao, Bingyu Zhang, Guoran Wan, Jie Gui, Meng Zhang, Baoxue Yang, Dilong Chen, Guoli Li and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Biogerontology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Mengna Wu *Department of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Shengyao Zhang *Department of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Xi ZhaoDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Bingyu ZhangDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Guoran WanDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Jie GuiDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Meng ZhangDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China.
Baoxue YangDepartment of Pharmacology, School of Basic Medical Sciences, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Dilong ChenChongqing Medical Products Administration, NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances, Chongqing, 401120, China.
Guoli LiChongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing Three Gorges Medical College, Chongqing, 404120, China.
Qiu ChenHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 6l0072, Sichuan Province, China. chenqiu1005@cdutcm.edu.cn.ORCID http://orcid.org/0000-0003-0090-7932
Boyue HuangDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China. boyue960521@cqmu.edu.cn.ORCID http://orcid.org/0000-0002-8065-3217
Jianhua RanDepartment of Anatomy, and Laboratory of Neuroscience and Tissue Engineering, Basic Medical College, Chongqing Medical University, Chongqing, China. ranjianhua@cqmu.edu.cn.ORCID http://orcid.org/0000-0001-9676-570X

Funding

Innovative Research Group Project of Natural Drug Antitumor of Chongqing Municipal Education Commission CXQT20030Key Project of Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area Sys20210007Key Project of Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area Sys20210008Key projects of Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area KFKT2022001Key projects of Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area KFKT2022010National Natural Science Foundation of China grants 81770738, 82370739Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission CSTB2023NSCQ-MSX0510Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission CSTB2024NSCQ-KJFZMSX0075Noncommunicable Chronic Diseases-National Science and Technology Major Project No.2023ZD0509400Science and Technology Research Program of Chongqing Municipal Education Commission No. KJQN202400417The Science and Technology Research Program of Chongqing Municipal Education Commission KJZD-M202202701
6 · The paper itself

Abstract

Aging is an inevitable physiological process characterized by progressive functional decline and degenerative alterations across organ systems. Metabolic disturbance, particularly the disruption of substance and energy metabolism, is increasingly recognized as a central hallmark of aging. Emerging evidence suggests that dysregulation of the urea cycle (UC) contributes to aging-related pathological processes, including cognitive impairment; however, its role in astrocyte-mediated brain aging remains unclear. In this study, we used a D-galactose-induced mouse aging model to investigate the involvement of UC activation in age-related cognitive decline. Aging mice exhibited marked cognitive impairment, accompanied by an increased proportion of reactive astrocytes in the hippocampus, a key pathological feature of brain aging. Metabolic analysis and molecular validation revealed enhanced UC activity and increased urea production in aging mice. Inhibition of UC activation reduced urea production and decreased the proportion of hippocampal reactive astrocytes. Mechanistically, the expression of key UC-related enzymes, including ornithine decarboxylase 1 (ODC1) and arginase 1 (ARG1), was significantly downregulated, accompanied by improved mitochondrial dynamics, particularly the restoration of mitochondrial fusion and fission balance. Furthermore, ODC1 knockdown confirmed its critical role in mediating UC activation in astrocytes and significantly alleviated aging-like cellular phenotypes. Notably, Ganoderma lucidum polysaccharide peptides (GLPs) effectively suppressed UC activation in aging astrocytes by downregulating ODC1 and ARG1. Collectively, this study identifies dysregulated astrocytic UC activity as a novel metabolic mechanism linking astrocyte reactivity, mitochondrial dysfunction, and age-related cognitive decline, suggesting that targeting ODC1-mediated UC activation and mitochondrial dynamics may provide a promising dual strategy for combating brain aging.

Indexed as

AgingAstrocytesMemory DisordersUreaAnimalsArginaseGalactoseHippocampusMaleMiceMice, Inbred C57BLArginaseGalactoseUreaAgingODC1Reactive astrocytesUrea cycleUT-B

Identifiers

PMID42640396

What OpenQuestion holds

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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.