Evidence mapPaperPMID 41721736Full record

ArticleAging cell2026

Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice.

Keru Ji, Hongde Wei, Ruguang Wang, Yutong Wu, Chen Li, Hongchang Gao, Liangcai Zhao

Abstract read
In one paragraph

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

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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

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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

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4 · The record

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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

7 authors.

Keru JiState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0009-0008-3349-8104
Hongde WeiState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0009-0009-9372-6401
Ruguang WangState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0009-0000-3909-2887
Yutong WuState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0009-0006-7341-7888
Chen LiState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0003-1947-0881
Hongchang GaoState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0003-3462-1879
Liangcai ZhaoState Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0001-5597-7407

Funding

National Natural Science Foundation of China 22274115National Natural Science Foundation of China 81770830Natural Science Foundation of Zhejiang Province LY22H070003
6 · The paper itself

Abstract

Brain aging is characterized by neuroinflammation and lactate metabolic changes. However, the functional role of FGF21 in the aging brain and its influence on lactate homeostasis remains unclear until now. In the study, male C57BL/6 mice were divided into 2-month-old (control), 20-month (aging), and FGF21-treated aging mice (FGF21). We also examined the MAPK signals and astrocyte-neuron lactate shuttle (ANLS) proteins in wild-type and hydroxycarboxylic acid receptor 1-knockout (HCA1-KO) mice with aging or long-term L-lactate infusion. In a mouse model of aging, neuronal FGF21 expression and ANLS rate were upregulated in hippocampal and cortical regions. Administration of exogenous FGF21 (1 mg/kg) to aging or lactate-infused mice can significantly improve learning and memory performance and the lactate metabolic microenvironment in an MCT2-dependent manner. Besides, HCA1-KO can significantly abolish both the CREB and MAPK signaling activation in lactate-infused mice, which differs from the scenario of aging mice. Furthermore, in vitro aging model further confirmed that p38-mediated FGF21 production and PI3K-mTOR-dependent MCT2 protein translation process, respectively. The increase in levels of FGF21 protein as the brain ages might help neurons cope with age-related neuroinflammation and lactate accumulation in mice. Our findings indicated that the shuttle rate of lactate and its microenvironment are related to neuronal function, which may be one therapeutic target for aging-related cognitive dysfunction.

Indexed as

AgingFibroblast Growth FactorsLactic AcidNeuroprotective AgentsAnimalsMaleMiceMice, Inbred C57BLMice, KnockoutNeuronsfibroblast growth factor 21Fibroblast Growth FactorsLactic AcidNeuroprotective AgentsagingANLSFGF21HCA1lactate homeostasisMCT2

Identifiers

PMID41721736
PMCPMC12928016

What Socratic 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 Socratic graph.