Evidence map›Paper›PMID 42523366›Full record

ArticlebioRxiv : the preprint server for biology2026

Targeting cellular senescence alleviates bone marrow aging.

Bowen Yan, Jin Han, Yang Yang, Peiyi Zhang, Jason O Brant, Jianhui Chang, Ha-Neui Kim, Maria Almeida, Prabhjot Kaur, Qingchen Yuan and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

17 authors.

Bowen YanDepartment of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA.ORCID 0000-0003-4730-6763
Jin HanTranslational Tissue Engineering Center, Department of Chemical and Biomolecular Engineering and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
Yang YangDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.
Peiyi ZhangDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Jason O BrantUniversity of Florida Health Cancer Institute, Gainesville, FL, USA.
Jianhui ChangDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
Ha-Neui KimDivision of Endocrinology, Department of Internal Medicine, Center for Musculoskeletal Disease Research and Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Maria AlmeidaDivision of Endocrinology, Department of Internal Medicine, Center for Musculoskeletal Disease Research and Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Prabhjot KaurDepartment of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA.
Qingchen YuanDepartment of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA.
Marco DemariaUniversity of Groningen (RUG), European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen (UMCG), Groningen, the Netherlands.
Kalyanee ShirlekarUniversity of Florida Health Cancer Institute, Gainesville, FL, USA.
Jennifer ElisseeffTranslational Tissue Engineering Center, Department of Chemical and Biomolecular Engineering and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
Guangrong ZhengUniversity of Florida Health Cancer Institute, Gainesville, FL, USA.
Ying LiangLindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
Daohong ZhouDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.ORCID 0000-0002-2400-6461
Olga A GuryanovaDepartment of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA.ORCID 0000-0002-6514-8466

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aging of the hematopoietic system impairs hematopoietic stem cell (HSC) function and alters bone marrow niche behavior, increasing susceptibility to anemia, infections, and hematologic malignancies. Here, pharmacologic clearance of senescent cells with the PROTAC compound 753b simultaneously targeting BCL-xL and BCL-2 reverses key secretory, transcriptional, and functional hallmarks of hematopoietic aging with low toxicity, restoring balanced lineage output. Single-cell RNA sequencing further demonstrates that 753b treatment attenuates aging-associated transcriptional signatures in HSCs, while selectively eliminating senescent, pro-survival niche cells without grossly perturbing niche composition. Functionally, 753b suppresses pro-inflammatory cues from both niche and hematopoietic cells including those emanating from neutrophil progenitors, rebalancing global bone marrow secretory ecosystem across stromal and hematopoietic compartments. Collectively, we identify 753b-induced senescent cell clearance as a powerful strategy to rejuvenate aged hematopoiesis and re-establish homeostatic communication between HSCs and their microenvironment, with implications for mitigating age-related hematologic dysfunction and improving hematologic health in older individuals.

Identifiers

PMID42523366
PMCPMC13405142

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.