Vascular Ageing: Mechanisms, Risk Factors, and Treatment Strategies

Abstract

Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage atherosclerosis, may trigger or exacerbate the development of age-related vascular diseases, which each year contribute to more than 3.8 million deaths in Europe alone and necessitate a better understanding of the mechanisms involved. To this end, a large number of recent preclinical and clinical studies have focused on the exponential accumulation of senescent cells in the vascular system and paid particular attention to the specific roles of senescence-associated secretory phenotype, proteostasis dysfunction, age-mediated modulation of certain microRNA (miRNAs), and the contribution of other major vascular risk factors, notably diabetes, hypertension, or smoking, to vascular ageing in the elderly. The data generated paved the way for the development of various senotherapeutic interventions, ranging from the application of synthetic or natural senolytics and senomorphics to attempt to modify lifestyle, control diet, and restrict calorie intake. However, specific guidelines, considering the severity and characteristics of vascular ageing, need to be established before widespread use of these agents. This review briefly discusses the molecular and cellular mechanisms of vascular ageing and summarises the efficacy of widely studied senotherapeutics in the context of vascular ageing.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

“…Advanced age affects the distribution of T-helper subtypes Th1 and Th2 in a distinct manner that increases Th2 lymphocyte numbers, and associated pro-inflammatory responses appear to play a pivotal role in atherosclerosis and atherothrombosis [77,78]. The innate immune responses dominated by monocytes/macrophages also play a key role in determining the balance between the progression and regression of atherosclerotic disease [79].…”

“…NK cells and cytotoxic T-cells play crucial roles in the recognition and clearance of senescent cells and damaged cells [80], but the age-related accumulation of NK cells may contribute to chronic low-grade inflammation, or inflammaging [81]. By accelerating cellular senescence and apoptosis, chronic low-grade inflammation may promote tissue degeneration, plaque instability, and barrier disruption, and constitute a key factor for vascular remodeling [78,82].…”

Saponins as therapeutic candidates for atherosclerosis

“…Endothelial senescence has emerged as a pivotal risk factor for the onset of CVDs, due to its distinctive secretory profile, pro‐inflammatory nature, and morphological alterations (Yin & Pickering, 2016). This senescence impairs endothelial function and exacerbates oxidative stress, which has been strongly implicated in the onset and progression of atherosclerosis (Ya & Bayraktutan, 2023). Notably, saponins showed positive anti‐atherosclerotic therapeutic ability by inhibiting endothelial senescence.…”

Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics

“…Manifestations of vascular aging include arterial and capillary stiffness, endothelial dysfunction, increased oxidative stress, decreased capacity for angiogenesis, early signs of atherosclerosis, and low-grade chronic inflammation ( Ghebre et al, 2016 ). Vascular aging constitutes a progressive decline in both the structural integrity and functional capacity of blood vessels, which contributes to damage to the heart, brain, kidneys, and other organs ( Climie et al, 2023 ; Ya and Bayraktutan, 2023 ). It is important that, while there is extensive literature on arterial aging and related diseases, there is a significant knowledge gap on venous aging.…”

“…At first, two big groups of senotherapeutic compounds were identified: senolytics and senomorphics. Senolytics selectively induce cell death of senescent cells, mostly by targeting elements of anti-apoptotic and pro-survival pathways of the cell (tyrosine kinases, Bcl-2 protein family, MDM2, FOXO4, HDACs) ( Table 3 ), while senomorphics modulate the SASP, responsible of many of the deleterious effects associated to senescence (by targeting telomerase, sirtuins, mTOR, NF-kB, ATM JAK/STAT, p38/MAPK) ( Table 4 ) ( Ya and Bayraktutan, 2023 ).…”