Mechanisms of aging in the cardiovascular system: challenges and opportunities

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  Figure 1. Cellular senescence is closely related to a variety of diseases throughout the body. In the cardiovascular system, cellular senescence leads to dysfunction of ECs, VSMCs, etc., which in turn increases the risk of diseases such as hypertension, AS, and cardiac infarction. In the nervous system, neuronal senescence may trigger neurodegenerative diseases, such as Alzheimer’s disease and Parkinson ‘s disease. In conclusion, cellular senescence accumulates in systemic tissues and becomes a potential trigger for a variety of diseases.

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  Figure 2. Overview of this review.

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  Figure 3. Signaling pathways and mechanisms of cellular senescence. Cellular senescence is a cellular state triggered by stress injury and some physiological processes, which is mainly divided into replicative senescence and non-replicative senescence. Replicative senescence is caused by telomere shortening due to continuous division of normal cells, and when telomeric DNA shortens to a certain extent, cells automatically turn on the ageing program and prevent cell cycle progression through the p53/p21 and p16INK4A/Rb signaling pathways. Non-replicative ageing can be triggered by various stress factors, and nuclear DNA damage is an important role. DNA damage-activated DDR can lead to p53 activation via ATM or ATR kinase activation, which in turn triggers cell cycle arrest. DDR can also induce SASP secretion via the cGAS-STING pathway. SASP components secreted by nearby senescent cells, such as IL-6, trigger the JAK-STAT signaling pathway, the so-called paracrine-induced senescence. In addition, mitochondrial dysfunction has been implicated as a driver of cellular senescence, mainly through three different mechanisms, which have been described in detail previously. ATM,…

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  Figure 4. Cardiovascular disease is associated with senescence of a variety of cells. Senescent cardiomyocytes mainly showed decreased fatty acid oxidation ability and enhanced glucose oxidation pathway. ECs are continuously exposed to unique injury-stimulating environments (blood flow pressure, blood flow shear stress, circulating factors, pathogenic stimuli, etc.) and are therefore highly susceptible to injury. In addition to being affected by DNA damage, oxidative stress, etc., SIRT6 deficiency and SIRT1 inactivation can lead to senescence in VSMCs. Under stress conditions, the phenotype of CFs is irreversibly altered, as shown by an increase in ageing markers such as α-SMA. Immune-related cells such as DCs, Macrophages, and T cells regulate the progression of cardiovascular disease mainly through changes in inflammatory factors. α-SMA, myofibroblast marker; Ang II, Angiotensin II; CPT1, carnitine palmitoyl transterase-1; SIRT1/6, Sirtuin 1/6.