Senescence-Associated Secretory Phenotype of Cardiovascular System Cells and Inflammaging: Perspectives of Peptide Regulation

Abstract

A senescence-associated secretory phenotype (SASP) and a mild inflammatory response characteristic of senescent cells (inflammaging) form the conditions for the development of cardiovascular diseases: atherosclerosis, coronary heart disease, and myocardial infarction. The purpose of the review is to analyze the pool of signaling molecules that form SASP and inflammaging in cells of the cardiovascular system and to search for targets for the action of vasoprotective peptides. The SASP of cells of the cardiovascular system is characterized by a change in the synthesis of anti-proliferative proteins (p16, p19, p21, p38, p53), cytokines characteristic of inflammaging (IL-1α,β, IL-4, IL-6, IL-8, IL-18, TNFα, TGFβ1, NF-κB, MCP), matrix metalloproteinases, adhesion molecules, and sirtuins. It has been established that peptides are physiological regulators of body functions. Vasoprotective polypeptides (liraglutide, atrial natriuretic peptide, mimetics of relaxin, Ucn1, and adropin), KED tripeptide, and AEDR tetrapeptide regulate the synthesis of molecules involved in inflammaging and SASP-forming cells of the cardiovascular system. This indicates the prospects for the development of drugs based on peptides for the treatment of age-associated cardiovascular pathology.

Free fatty acid receptor 4 in cardiac myocytes ameliorates ischemic cardiomyopathy

“…Senescent cells are also characterized by a senescence-associated secretory phenotype (SASP), and in heart this can include anti-proliferative proteins, pro-inflammatory molecules, matrix metalloproteinases, adhesion molecules and sirtuins. 34, 35 Analysis of the transcriptome data identified a specific SASP associated with the loss of Ffar4 in the infarcted myocardium (Table 3).…”

Cellular senescence in cancer: molecular mechanisms and therapeutic targets

“…Apart from the features described above, senescent cells remain metabolically active and develop a hypersecretory phenotype, SASP, another key hallmark of senescence that allows them to communicate with and affect neighboring cells 152 . SASP components can be broadly categorized into three groups: extracellular proteases, secreted insoluble protein/nonprotein components, and soluble signaling molecules (interleukins [ILs], chemokines, and growth factors) 153,154 . In this section, the major components of the SASP, the upstream mechanisms that modulate their formation and secretion, and their role in the tumor microenvironment (TME) are presented.…”

“… 152 SASP components can be broadly categorized into three groups: extracellular proteases, secreted insoluble protein/nonprotein components, and soluble signaling molecules (interleukins [ILs], chemokines, and growth factors). 153 , 154 In this section, the major components of the SASP, the upstream mechanisms that modulate their formation and secretion, and their role in the tumor microenvironment (TME) are presented.…”

Senescence-Induced Atherosclerosis: The Potency of Senolytic Therapy

“…This is because as people age, their immune cell function tends to deteriorate, a process known as immunosenescence, which is particularly common among the elderly. 9…”

“…26,27Senescence-associated secretory phenotype (SASP)The term SASP refers to a complex secretion profile generated by cells undergoing senescence. The recognized categorization of SASP components includes signaling factors, proteases, extracellular matrix (ECM) proteins, and non-protein constituents.Based on their molecular mode of action, these components encompass receptor-interacting entities such as soluble signaling molecules like cytokines, chemokines, and growth factors; molecules that act directly like non-protein elements, ROS, and nitric oxide; and regulatory factors such as matrix metalloprotease inhibitors and plasminogen activator inhibitors 9. The composition and potency of SASP exhibit considerable variability, contingent upon factors including the trigger and length of time of stressor, environmental cues, and type of cell.28 The Senescence-Associated Secretory Phenotype(SASP) undergoes initial regulation mainly at the transcriptional level.…”