Cellular senescence and senotherapeutics in cardiovascular diseases

Jul 27, 2025Advances in pharmacology (San Diego, Calif.)

Cell aging and treatments targeting aging cells in heart and blood vessel diseases

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Abstract

Cellular senescence is associated with the progression of age-related cardiovascular diseases.

Cardiac senescent cells accumulate in the cardiovascular system and contribute to conditions such as heart failure and coronary artery disease.
These senescent cells release inflammatory factors and profibrotic agents that exacerbate cardiovascular pathologies.
Key factors leading to cellular senescence include oxidative stress, metabolic dysfunction, telomere shortening, and epigenetic changes.
Senotherapies may provide a novel approach to target mechanisms of cellular senescence and potentially prevent cardiovascular diseases in the elderly.
Therapeutic strategies include senolytics to selectively eliminate senescent cells, SASP suppressors to reduce inflammatory factors, and methods to inhibit the increase of senescent cells.

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Cellular senescence (CS) is characterized by stable cell cycle arrest and is resistant to growth-promoting stimuli allied with aging. Cardiac senescent cells (SCs) are highly heterogeneous cells that can regulate the pathophysiology of cardiovascular diseases (CVDs). SCs accumulate in the cardiovascular system, leading to typical age-related cardiovascular conditions. Such conditions advance in cardiovascular pathologies, including heart failure, coronary artery disease, cardiac fibrosis, etc., by evocating the production of proinflammatory mediators and profibrotic senescence-associated secretory phenotype (SASP). SCs release different factors depending on the cell type that became senescent. Many factors are responsible for CS with the aging process. The primary senescence causes are oxidative stress, metabolic dysfunction, telomere shortening, and epigenetic deregulation. However, it isn't easy to understand the molecular mechanisms that lead to CS and the consequences of CS in developing new strategies and therapeutic approaches to treat CVDs. Among all, senotherapies are an emerging approach for intervening against CS mechanisms in CVDs to potentially prevent and treat CVDS. Senotherapies allow targeting the underlying causes of aging rather than treating disorders and could reduce polypharmacy. Essentially, senotherapeutics represent an emerging anti-SC treatment and comprise three therapeutic approaches such as molecules to selectively kill SCs that are defined senolytics, compounds able to reduce evocated SC SASP, acting hence as SASP suppressors, called senomorphics, and inhibition of increase of the number of SCs in the cardiovascular tissues. Senotherapies might delay or prevent the CVDs in the elderly. Therefore, senotherapeutics represent the potential clinical application in CVDs, stressing benefits and signifying potential solutions for applying them as soon as effective anti-CVD treatments.

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Cellular senescence and senotherapeutics in cardiovascular diseases

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