Evidence mapPaperPMID 40974022Full record

ArticleAging cell2025

DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains.

Yaru Liu, Pan Liao, Bo Yan, Dai Li, Shishuang Zhang, Wei Zhang, Zexi Jia, Zihan Zhang, Han Gao, Qiang Liu and 3 more

Abstract read
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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.

Yaru LiuDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Pan LiaoTianjin Institute of Geriatrics, Tianjin, China.
Bo YanDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.ORCID 0000-0003-0674-197X
Dai LiDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Shishuang ZhangDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Wei ZhangDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Zexi JiaDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Zihan ZhangTianjin Institute of Geriatrics, Tianjin, China.
Han GaoDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Qiang LiuDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Fanglian ChenDepartment of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China.
Ping LeiDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Zhenyu YinDepartment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.ORCID 0000-0002-1763-8460

Funding

National Natural Science Foundation of China 82271401Tianjin Municipal Education Commission Scientific Research Plan Project 2023KJ114
6 · The paper itself

Abstract

Aging leads to neurodegenerative diseases, such as cognitive decline, which are induced by persistent chronic low-grade inflammation in the brain driven by microglial activation. However, whether and how brain-derived exosomes from aged mice (A-exo) induce a pro-inflammatory state and cellular senescence in microglia within the aging brain is poorly understood. Here, we report that brain-derived exosomes from aged mice (A-exo) cause cognitive decline in normal young mice, inducing microglial overactivation, lipid droplet accumulation, and senescence-associated secretory phenotype (SASP) secretion. This abnormal microglial activity arises from the elevated expression of PTGDS in A-exo due to mouse aging, resulting in increased central and peripheral D-prostanoid receptor 1 (DP1) ligand PGD2 levels, which subsequently leads to sustained DP1 signaling activation. Consequently, this process promotes myeloid cell infiltration, cellular senescence, and cognitive decline by generating a senescent, pro-inflammatory microglial phenotype. Blocking the DP1 receptor ameliorates A-exo-mediated microglial overactivation, myeloid cell infiltration, and cellular senescence. Strikingly, DP1 receptor blockade improves cellular senescence, neuroinflammation, and cognitive decline in aged mice. Our findings reveal a systemic mechanism underlying the sustained activation of microglia following brain aging, paving the way for improving chronic neuroinflammation, cellular senescence, and cognitive decline associated with aging.

Indexed as

AgingBrainCellular SenescenceCognitive DysfunctionExosomesMicrogliaReceptors, ProstaglandinAnimalsMaleMiceMice, Inbred C57BLReceptors, ProstaglandinagingDP1 receptorsexosomesmicroglianeuroinflammation

Identifiers

PMID40974022
PMCPMC12610410

What Socratic holds

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Registered trials

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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.