Chronic Intermittent Hypoxia Triggers a Senescence-like Phenotype in Human White Preadipocytes

Author(s)

Polonis, Katarzyna ^[1] ; Becari, Christiane ^{[1, 2]} ; Chahal, C. Anwar A. ^{[1, 3]} ; Zhang, Yuebo ^[1] ; Allen, Alina M. ^[4] ; Kellogg, Todd A. ^[5] ; Somers, Virend K. ^[1] ; Singh, Prachi ^{[6, 1]}

Affiliation

^[1] Mayo Clin, Dept Cardiovasc Med, Rochester, MN 55902 - USA

^[2] Ribeirao Preto Med Sch, Dept Surg & Anat, Ribeirao Preto, SP - Brazil

^[3] Mayo Clin, Grad Sch Biomed Sci, Rochester, MN - USA

^[4] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN - USA

^[5] Mayo Clin, Dept Surg, Rochester, MN - USA

^[6] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 APR 22 2020.
• Web of Science Citations: 0

Abstract

Obstructive sleep apnea (OSA) is a common sleep disorder associated with obesity. Emerging evidence suggest that OSA increases the risk of cardiovascular morbidity and mortality partly via accelerating the process of cellular aging. Thus, we sought to examine the effects of intermittent hypoxia (IH), a hallmark of OSA, on senescence in human white preadipocytes. We demonstrate that chronic IH is associated with an increased generation of mitochondrial reactive oxygen species along with increased prevalence of cells with nuclear localization of gamma H2AX \& p16. A higher prevalence of cells positive for senescence-associated beta-galactosidase activity was also evident with chronic IH exposure. Intervention with aspirin, atorvastatin or renin-angiotensin system (RAS) inhibitors effectively attenuated IH-mediated senescence-like phenotype. Importantly, the validity of in vitro findings was confirmed by examination of the subcutaneous abdominal adipose tissue which showed that OSA patients had a significantly higher percentage of cells with nuclear localization of gamma H2AX \& p16 than non-OSA individuals (20.1 +/- 10.8% vs. 10.3 +/- 2.7%, P-adjusted<0.001). Furthermore, the frequency of dual positive gamma H2AX \& p16 nuclei in adipose tissue of OSA patients receiving statin, aspirin, and/or RAS inhibitors was comparable to non-OSA individuals. This study identifies chronic IH as a trigger of senescence-like phenotype in preadipocytes. Together, our data suggest that OSA may be considered as a senescence-related disorder. (AU)

• FAPESP's process: 18/23718-8 - Role of renin angiotensin system in abdominal aortic aneurysm
• Grantee: Christiane Becari
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 17/21539-6 - Role of renin angiotensin system in Abdominal Aortic Aneurysm
• Grantee: Christiane Becari
• Support Opportunities: Research Grants - Young Investigators Grants