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 04 15.
Article
en En
| MEDLINE
| ID: mdl-38113165
ABSTRACT
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.Methods:
We compared the effects of 6 weeks of therapy with either partial normoxic recovery alone or combined with the senolytic navitoclax after 16 weeks of intermittent hypoxia exposures, a hallmark of OSA, on multiphenotypic cardiometabolic and neurocognitive parameters.Measurements and MainResults:
Our findings indicate that only when combined with navitoclax, partial normoxic recovery significantly improved sleepiness (sleep in the dark phase 34% ± 4% vs. 26% ± 3%; P < 0.01), cognition (preference score 51% ± 19% vs. 70% ± 11%; P = 0.048), 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 is not only contingent on restoration of normal oxygenation patterns but can be further enhanced by targeting other OSA-mediated detrimental cellular processes, such as accelerated senescence.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Apnea Obstructiva del Sueño
/
Senoterapéuticos
/
Compuestos de Anilina
Límite:
Animals
Idioma:
En
Revista:
Am J Respir Crit Care Med
Asunto de la revista:
TERAPIA INTENSIVA
Año:
2024
Tipo del documento:
Article