Evidence map›Paper›PMID 42624917›Full record

ArticleNature aging2026

Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.

Adarsh Rajesh, Aaron P Havas, Rouven Arnold, Kathryn Lande, Xue Lei, Kelly Yichen Li, Armin Gandhi, Ana Catarina Franco, Seung-Hwa Woo, Anthony B Lagnado and 37 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature aging, 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

5 · Who and what money

Authors and funding

47 authors.

Adarsh RajeshSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0009-0003-4326-7442
Aaron P HavasSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4291-8015
Rouven ArnoldSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Kathryn LandeSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Xue LeiSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Kelly Yichen LiSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Armin GandhiSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-8246-4663
Ana Catarina FrancoMayo Clinic, Department of Physiology and Biomedical Engineering, Rochester, MN, USA.
Seung-Hwa WooMayo Clinic, Department of Physiology and Biomedical Engineering, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-9336-4457
Anthony B LagnadoMayo Clinic, Department of Physiology and Biomedical Engineering, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-9380-5179
Angela LiouSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
K Garrett EvensenSalk Institute for Biological Studies, Integrative Genomics and Bioinformatics Core, La Jolla, CA, USA.
Linshan LauxMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota Medical School, Minneapolis, MN, USA.
Maggie KlaersMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota Medical School, Minneapolis, MN, USA.
Jake KircherMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota Medical School, Minneapolis, MN, USA.
Amirhossein Nayeri RadLudwig Boltzmann Institute for Traumatology, The Research Center (in cooperation with AUVA), Vienna, Austria.
Hiroshi TanakaSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Marcos Garcia TenecheSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4785-7987
Michael AlcarazSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Karl N MillerSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Zoe YaoSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0009-0007-6236-8395
Sviatlana ZaretskiSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Sainath MamdeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Qian YangDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0004-1911-8874
Jessica ProulxSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5452-0461
Andrew DavisSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Laurence HaddadinSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0009-0006-2359-4288
Carolina Cano MacipSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0009-0000-3905-2973
Brightany LiSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Nirmalya DasguptaSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Zong Ming ChuaSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Cedomir StamenkovicCardiovascular and Muscular Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Gabriele GuarnacciaCardiovascular and Muscular Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Hideki TanizawaInstitute for Genetic Medicine, Hokkaido University, Sapporo, Japan.ORCID http://orcid.org/0000-0002-2573-2473
Charlene MicianoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Elizabeth SmootDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Allen WangDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9870-7888
Rebecca A PorrittSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-0973-5092
Alessandra SaccoSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-1669-0221
Ken-Ichi NomaInstitute for Genetic Medicine, Hokkaido University, Sapporo, Japan.ORCID http://orcid.org/0000-0002-5187-6788
Jeffrey H AlbrechtDivision of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0009-0002-6268-0315
Laura J NiedernhoferMasonic Institute on the Biology of Aging and Metabolism, University of Minnesota Medical School, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-1074-1385
Joao F PassosMayo Clinic, Department of Physiology and Biomedical Engineering, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-8765-1890
April E WilliamsSalk Institute for Biological Studies, Integrative Genomics and Bioinformatics Core, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9281-8528
Bing RenNew York Genome Center, New York, NY, USA.
Kevin Y YipSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5516-9944
Peter D AdamsSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. padams@sbpdiscovery.org.ORCID http://orcid.org/0000-0002-0684-1770

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Alan Saghatelian · 1985 to 2026
$82.8M
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
San Diego Nathan Shock CenterP30AG068635 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI SHADEL, GERALD · 2020 to 2024
$6.0M
The role of sub-lethal mitochondrial apoptotic stress in cellular senescenceR01AG068048 · NIA · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2020 to 2024
$2.2M
Development of machine learning software to quantitatively map telomere induced senescence in tissue sections during agingUH3CA268103 · NCI · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2023 to 2025
$1.6M
Investigating the role of cytosolic mitochondrial double-stranded RNA in cellular senescence and agingR01AG082708 · NIA · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2023 to 2025
$1.5M
Development of machine learning software to quantitatively map telomere induced senescence in tissue sections during agingUG3CA268103 · NCI · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2021 to 2022
$1.1M
Mitonuclear signaling pathways in senescence-associated inflammationK99AG073450 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLER, KARL NATHAN · 2022 to 2023
$236k
California Institute for Regenerative Medicine (CIRM) EDUC-4-12813NCI NIH HHS UG3 CA268103NCI NIH HHS UH3 CA268103NIA NIH HHS R01 AG068048NIA NIH HHS R01 AG082708U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30 CA014195U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) K99 AG073450U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P01 AG031862U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P01 AG073084U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P30 AG068635U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U54 AG079758
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), including interferon-stimulated genes (ISGs). Here we confirm and extend previous observations that cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated across models of nonproliferating senescent 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 that activate pro-inflammatory cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling. In aged mouse livers, senescent hepatocytes show increased Ccnd1 expression. Hepatocyte-specific Ccnd1 knockout or treatment with the clinical grade CDK4/6 inhibitor palbociclib reduces DNA damage and ISGs in aged mouse liver. Further, palbociclib suppresses frailty and improves physical performance of aged mice. These findings demonstrate a role for CCND1/CDK6 in regulating DNA damage and inflammation in senescence and aging, highlighting it as a promising target for therapeutic repurposing.

Indexed as

AgingCellular SenescenceCyclin D1Cyclin-Dependent Kinase 6InflammationAnimalscGAS-STING Signaling PathwayDNA DamageHepatocytesHumansLiverMaleMiceMice, KnockoutPiperazinesPyridinesCcnd1 protein, mouseCdk6 protein, mouseCyclin D1Cyclin-Dependent Kinase 6palbociclibPiperazinesPyridines

Identifiers

PMID42624917

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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.