Obesity induces signs of premature cardiac aging in younger patients: the role of mitochondria

Abstract

Objectives: The purpose of the present study was to investigate the influence of obesity on cardiac aging.

Background: Obesity is associated with an increased incidence of left ventricular hypertrophy, diastolic dysfunction, heart failure, and atherosclerosis.

Methods: Sixty male cardiac surgery patients were included in the study according to body mass index (18.5 to 25 kg/m²: normal weight; 30 to 35 kg/m²: obese) and age (<55 years: young; >70 years: old) and divided into 4 groups of 15 patients each. Right atrial cardiomyocytes were analyzed for mitochondrial function, markers of apoptosis, cardiac load or metabolism, and oxidative stress parameters. The metabolic state was further characterized in fasting blood samples.

Results: Obesity resulted in disturbed mitochondrial biogenesis and function (respiratory chain complex I) in the cardiomyocytes of young and old patients. Disturbed mitochondrial function was associated with signs of increased oxidative stress (protein carbonyl content, 8-hydroxy-2'-deoxyguanosine) as well as telomere shortening by up to 30%. Cardiomyocytes from older (obese and normal-weight) and young obese patients demonstrated higher levels of load-induced markers (atrial natriuretic peptide and brain natriuretic peptide) and proapoptotic activation with increased Bax and Bcl-xS expression, cytochrome C release, and caspase 3/9 activation. Disturbances in glucose metabolism and adipocytokine release were detectable in old (obese and normal-weight) and young obese patients. However, only minor deteriorations in most parameters were observed in obese subjects older than 70 years of age compared with normal-weight, age-matched patients.

Conclusions: These data indicate that obesity results in premature cardiac aging in younger patients, which may contribute to an increased risk for heart failure.