Evidence map›Paper›PMID 40766702›Full record

ArticlebioRxiv : the preprint server for biology2025

Targeting CyclinD1-CDK6 to Mitigate Senescence-Driven Inflammation and Age-Associated Functional Decline.

Adarsh Rajesh, Aaron P Havas, Rouven Arnold, Kathryn Lande, K Garrett Evensen, Kelly Yichen Li, Sainath Mamde, Qian Yang, Armin Gandhi, Karl N Miller and 17 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Adarsh RajeshSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.ORCID 0009-0003-4326-7442
Aaron P HavasSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Rouven ArnoldSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Kathryn LandeSalk Institute for Biomedical Studies, Integrative Genomics and Bioinformatics Core, La Jolla, CA.
K Garrett EvensenSalk Institute for Biomedical Studies, Integrative Genomics and Bioinformatics Core, La Jolla, CA.
Kelly Yichen LiSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Sainath MamdeUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Qian YangUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Armin GandhiSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Karl N MillerSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Marcos Garcia TenecheSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Zoe YaoSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Jessica ProulxSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Andrew DavisUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Laurence HaddadinSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Michael AlcarazSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Carolina C MacipSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Brightany LiSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Xue LeiSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Charlene MicianoUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Elizabeth SmootUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Allen WangUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Jeffrey H AlbrechtUniversity of Minnesota, Department of Medicine, Minneapolis, MN.
April E WilliamsSalk Institute for Biomedical Studies, Integrative Genomics and Bioinformatics Core, La Jolla, CA.
Bing RenUniversity of California San Diego, Department of Cellular and Molecular Medicine, La Jolla, CA.
Kevin Y YipSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.
Peter D AdamsSanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA.

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
STRUCTURAL BASIS FOR EPIGENETICS IN AGING AND LONGEVITYP01AG031862 · NIA · WISTAR INSTITUTE · PI SCHULTZ, DAVID C · 2008 to 2022
$28.3M
Project 4: Interrogating and harnessing age-related IFN signaling and innate immunity in HCC prevention and therapyP01AG073084 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI PETER D. ADAMS, GERALD SHADEL · 2021 to 2026
$13.6M
Spatial Mapping Senescent Cells Across the Mouse Lifespan by Multiplex Transcriptomics and EpigenomicsU54AG079758 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI PETER D. ADAMS · 2022 to 2026
$12.1M
Beckman Coulter Biomek i7 Hybrid automated workstationS10OD036254 · OD · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI HUANG, CHUN-TENG · 2024 to 2024
$594k
Mitonuclear signaling pathways in senescence-associated inflammationK99AG073450 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLER, KARL NATHAN · 2022 to 2023
$236k
NCI NIH HHS P30 CA030199NIA NIH HHS K99 AG073450NIA NIH HHS P01 AG031862NIA NIH HHS P01 AG073084NIA NIH HHS U54 AG079758NIH HHS S10 OD036254
6 · The paper itself

Abstract

Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the Senescence Associated Secretory Phenotype (SASP) and interferon-stimulated genes (ISGs). Cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated in these non-proliferating cells. We show that CCND1 and its kinase partner CDK6 drive SASP and ISG expression in senescent cells by promoting DNA damage accumulation. This leads to the formation of cytoplasmic chromatin fragments (CCFs) that activate pro-inflammatory CGAS-STING signaling. The tumor suppressor p53 (TP53) and its target p21 (CDKN2A) antagonize this CCND1-CDK6-dependent DNA damage accumulation pathway to suppress the SASP. In aged mouse livers, senescent hepatocytes show increased Ccnd1 expression. Hepatocyte-specific

Identifiers

PMID40766702
PMCPMC12324409

What OpenQuestion 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 OpenQuestion graph.