Obesity Induces Signs of Premature Cardiac Aging in Younger Patients

Niemann, Bernd; Chen, Ying; Teschner, M; Li, Ling; Silber, Rolf-Edgar; Rohrbach, Susanne

doi:10.1016/j.jacc.2010.09.040

Cited by 148 publications

(140 citation statements)

References 33 publications

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“…Data on age-related changes in obesity has led some researchers to postulate that obesity could be considered as a condition of premature metabolic dysfunction resembling ageing (Tchkonia et al 2010;Burt Solorzano and McCartney 2010;Niemann et al 2011). Other studies claim that molecular pathways of regulation involved in obesity and ageing are divergent and specific or at least not overlapping (Miard and Picard 2008).…”

Section: Ageingmentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

344

203

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Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

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Section: Ageingmentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

344

203

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“…This change in the endothelium is associated with cellular senescence, which is a stress response characterized by irreversible cell cycle exit and an altered secretory proteome profile (Coppe, Desprez, Krtolica, & Campisi, 2010). Well‐known molecular triggers for the senescence response include attrited telomeres, exposure to sublethal genotoxic stress, and activation of the DNA damage response (DDR) or oncogene signals (Imanishi, Hano, Sawamura, & Nishio, 2004; Mistriotis & Andreadis, 2017; Niemann et al., 2011). In addition, traditional cardiovascular risk factors have been shown to induce premature cardiovascular senescence (Erusalimsky, 2009).…”

Section: Introductionmentioning

confidence: 99%

Human electronegative LDL induces mitochondrial dysfunction and premature senescence of vascular cells in vivo

et al. 2018

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SummaryDysregulation of plasma lipids is associated with age‐related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low‐density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg−1 day−1) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence‐associated β‐galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5‐treated but not L1‐treated mice. Similar to that, in Syrian hamsters with elevated serum L5 levels induced by a high‐fat diet, nuclear γH2AX deposition and senescence‐associated β‐galactosidase staining were increased in the aortic endothelium. This phenomenon was blocked in the presence of N‐acetyl‐cysteine (free‐radical scavenger) or caffeine (ATM blocker), as well as in lectin‐like oxidized LDL receptor‐1 (LOX‐1) knockout mice. In cultured human aortic endothelial cells, L5 augmented mitochondrial oxygen consumption and mitochondrial free‐radical production, which led to ATM activation, nuclear γH2AX deposition, Chk2 phosphorylation, and TP53 stabilization. L5 also decreased human telomerase reverse transcriptase (hTERT) protein levels and activity. Pharmacologic or genetic manipulation of the reactive oxygen species (ROS)/ATM/Chk2/TP53 pathway efficiently blocked L5‐induced endothelial senescence. In conclusion, L5 may promote mitochondrial free‐radical production and activate the DNA damage response to induce premature vascular endothelial senescence that leads to atherosclerosis. Novel therapeutic strategies that target L5‐induced endothelial senescence may be used to prevent and treat atherosclerotic vascular disease.

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“…Moreover, cardiomyocyte senescence is implicated in the myocardial damage caused by doxorubicin and obesity 16, 17. However, as the primary cell population that constitutes ≈75% of the myocardium volume,18 the contribution of cardiomyocyte senescence to heart remodeling has not been thoroughly elucidated to date.…”

Section: Introductionmentioning

confidence: 99%

Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA4‐Dependent CCN1 Secretion

Cui

Xue

Yang

et al. 2018

JAHA

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BackgroundStress‐induced cell premature senescence participates in a variety of tissue and organ remodeling by secreting such proteins as proinflammatory cytokines, chemokines, and growth factors. However, the role of cardiomyocyte senescence in heart remodeling after acute myocardial infarction has not been thoroughly elucidated to date. Therefore, we sought to clarify the impact of premature myocardial senescence on postinfarction heart function.Methods and ResultsSenescence markers, including p16INK 4a, p21CIP 1/ WAF 1, and SA‐β‐gal staining, were analyzed in several heart disease models by immunostaining. Both postinfarction mouse hearts and ischemic human myocardium demonstrated increased senescence markers. Additionally, senescence‐related secretory phenotype was activated after acute myocardial infarction, which upregulated senescence‐related secretory phenotype factors, including CCN family member 1 (CCN1), interleukin‐1α, tumor necrosis factor α, and monocyte chemoattractant protein‐1. In vivo, a tail vein injection of AAV9‐Gata4‐shRNA significantly attenuated senescence‐related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence‐related secretory phenotype factors, CCN1 administration reduced myofibroblast viability in vitro and rescued the deleterious effect of AAV9‐Gata4‐shRNA in vivo.ConclusionsMyocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA‐binding factor 4‐CCN1 pathway.

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Obesity Induces Signs of Premature Cardiac Aging in Younger Patients

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

Cited by 148 publications

References 33 publications

Obesity and related consequences to ageing

Obesity and related consequences to ageing

Human electronegative LDL induces mitochondrial dysfunction and premature senescence of vascular cells in vivo

Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA4‐Dependent CCN1 Secretion

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