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Aging and Cardiovascular Diseases: The Role of Cellular Senescence

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Oxidative Stress in Heart Diseases

Abstract

Aging, which is associated with several undesirable processes, is a complex phenomenon. Aging mechanisms are not fully comprehended yet, however, diseased and aged cells are correlated with accumulation of senescent cells. Various studies have revealed that aging leads to structural and functional changes in cardiac cells. During aging, stresses such as telomere shortening and reactive oxygen species (ROS) induce cellular senescence which is characterized by permanent cell cycle arrest and secretion of inflammatory proteins that affect tissue environment. Especially, the effect of oxidative stress and ROS generation on macromolecules have been considered important in the modulation of various age-associated chronic disorders and the lifespan. Recent studies have shown the presence senescent phenotype in endothelial cells and smooth muscle cells of patients with heart failure, diabetes, and atherosclerosis. Existence of senescent vascular cells indicates that cellular senescence has a causative role in the pathology of cardiovascular diseases. There is also accumulating evidence that impairment in systemic metabolism is connected by cellular senescence. Therefore, clearance of senescent cells or suppression of cellular senescence is suggested as an important field for future investigation and the discovery of senolytics is seen as a promising therapy of vascular diseases. This chapter describes the phenomenon of cellular senescence with emphasis to its link to oxidative stress during aging and its essential role on the pathology of the vascular system.

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Abbreviations

AAA:

Abdominal aortic aneurysm

CVD:

Cardiovascular disease

DDR:

DNA damage response

DNA:

Deoxyribonucleic acid

EC:

Endothelial cells

ER:

Endoplasmic reticulum

ETC:

Electron transport chain

HFpEF:

Heart failure with a preserved ejection fraction

IL:

Interleukin

Keap1:

Kelch-like ECH associated protein 1

LV:

Left ventricular

MCP:

Monocyte chemoattractant protein 1

mTOR:

Mammalian target of rapamycin

NAD:

Nicotinamide adenine dinucleotide

NFκB:

Nuclear factor kappa B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOX:

NADPH oxidases

Nrf2:

Nuclear factor erythroid 2–related factor 2:

oxLDL:

Oxidized low-density lipoproteins:

PGC-1α:

PPAR-γ coactivator 1 alpha

ROS:

Reactive oxygen species

SAHF:

Senescence-associated heterochromatin foci

SAMP8:

Senescence accelerated mice prone 8

SASP:

Senescence-associated secretory phenotype:

SA-β-gal:

Senescence-associated beta-galactosidase

SIPS:

Stress-induced premature senescence

SIRT:

Sirtuin

SMC:

Smooth muscle cells

SOD:

Superoxide dismutase

TGFβ:

Transforming growth factor β

TNFα:

Tumor necrosis factor

VSMC:

Vascular smooth muscle cell

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Acknowledgment

This work was supported by The Scientific and Technological Council of Turkey (TUBITAK) 2219 Grant Program.

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Bozaykut, P. (2019). Aging and Cardiovascular Diseases: The Role of Cellular Senescence. In: Chakraborti, S., Dhalla, N., Ganguly, N., Dikshit, M. (eds) Oxidative Stress in Heart Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-13-8273-4_10

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