PXD046854

PXD046854 is an original dataset announced via ProteomeXchange.

Title	Senolytic-Facilitated Reversal of End-Organ Dysfunction in a Murine Model of Obstructive Sleep Apnea
Description	Rationale: Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with accelerated biological aging and multiple end-organ morbidities. Current treatments, such as continuous positive airway pressure (CPAP), have shown limited cognitive, metabolic, and cardiovascular beneficial outcomes despite adherence. Thus, adjunct therapies aiming to reduce OSA burden, such as senolytics, could improve OSA outcomes. Objectives: To assess if targeting senescence in addition to partial normoxia mimicking “good” CPAP adherence can improve physiological outcomes in mice exposed to chronic intermittent hypoxia (IH). Methods: We compared the effects of 6 weeks therapy with either partial normoxic recovery alone or combined with the senolytic Navitoclax (NAV) after 16 weeks of IH exposures, a hallmark of OSA, on multi-phenotypic cardiometabolic and neurocognitive parameters. Results: Our findings indicate that only when combined with NAV, partial normoxic recovery significantly improved wakefulness (sleep in the dark phase: 34 ± 4% vs. 24 ± 3%, p < 0.01), cognition (Preference score: 51 ± 19% vs. 70 ± 11%, p < 0.05), coronary artery function (response to acetylcholine (vasodilation): 56 ± 13% vs. 72 ± 10%, p < 0.001), glucose, and lipid metabolism, and reduced intestinal permeability and senescence in multiple organs. Conclusions: These findings indicate that the reversibility of end-organ morbidities induced by OSA are not only contingent on restoration of normal oxygenation patterns and can be further enhanced by targeting other OSA-mediated detrimental cellular processes, such as accelerated senescence.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:08:28.849.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brian Mooney
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-10 12:15:09	ID requested
⏵ 1	2025-05-06 12:08:29	announced

10.1164/rccm.202306-1101oc;

Badran M, Puech C, Khalyfa A, Cortese R, Cataldo K, Qiao Z, Gozal D, Senolytic-facilitated Reversal of End-Organ Dysfunction in a Murine Model of Obstructive Sleep Apnea. Am J Respir Crit Care Med, 209(8):1001-1012(2024) [pubmed]

submitter keyword: normoxia,sleep apnea, intermittent hypoxia, senescence

Abdelnaby Khalyfa
contact affiliation	Department of Child Health and Child Health Research Institute, School of Medicine, University of Missouri, Columbia, MO, United States
contact email	khalyfaa@missouri.edu
lab head
Brian Mooney
contact affiliation	University of Missouri, Columbia
contact email	mooneyb@missouri.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046854
     1. Label: PRIDE project
     2. Name: Senolytic-Facilitated Reversal of End-Organ Dysfunction in a Murine Model of Obstructive Sleep Apnea