Evidence map›Paper›PMID 40832280›Full record

ArticlebioRxiv : the preprint server for biology2025

Paracrine Bone-Derived Senescent Secretome Induces Spatially Patterned ECM and Biomechanical Vulnerability in Human Brain Organoids.

Chanul Kim, Luke Daniel Ofria, Anannya Kshirsagar, Elizabeth Gomez Flores, Sai Kulkarni, Alan Y Liu, James L Kirkland, Annie Kathuria, Maryam Tilton

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. 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

9 authors.

Chanul KimDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Luke Daniel OfriaDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Anannya KshirsagarDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Elizabeth Gomez FloresDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Sai KulkarniDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Alan Y LiuOptics11 Life Inc., Boston, Massachusetts, USA.
James L KirklandCenter for Advanced Gerotherapeutics, Division of Endocrinology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Annie KathuriaDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Maryam TiltonWalker Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX, USA.

Funding

Effect of Aging on Preadipocyte DifferentiationR37AG013925 · NIA · MAYO CLINIC ROCHESTER · PI KIRKLAND, JAMES L. · 2016 to 2025
$6.6M
Impact of Local vs. Systemic Senescent Bone Cell Accumulation on Healthy Osteocyte MechanosensationK25AG095370 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI Maryam Tilton · 2025 to 2026
$292k
NIA NIH HHS K25 AG095370NIA NIH HHS R37 AG013925
6 · The paper itself

Abstract

Aging is increasingly recognized as a systemic process, yet the mechanisms by which senescent cells' signal from peripheral tissues accelerate brain aging remain poorly defined. Here, we used chronic exposure of human cerebral organoids to the secretome of senescent osteocytes to investigate how peripheral aging signals reshape brain tissue architecture. We combined spatially resolved optical fiberbased interferometry nanoindentation with transcriptomic and immunofluorescence profiling, demonstrating that bone-derived senescence-associated secretory phenotype (SASP) factors induce a biphasic mechanical response, early global tissue softening, followed by the emergence of discrete hyper-stiff microdomains. This spatially heterogeneous biomechanical remodeling was accompanied by upregulation of extracellular matrix (ECM), inflammatory, and senescence pathways, and suppression of neurodevelopmental and synaptic gene networks. Our results reveal that chronic paracrine SASP exposure from senescent osteocytes drives localized ECM reorganization and mechanical vulnerability in human brain tissue, providing mechanistic insight into how peripheral cellular senescence may contribute to regional brain fragility during aging.

Identifiers

PMID40832280
PMCPMC12363841

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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.