Is it the time of seno-therapeutics application in cardiovascular pathological conditions related to ageing?

Abstract

It rates that in 2030, the cardiovascular diseases (CVD) will result in 40% of all deaths and rank as the leading cause. Thus, the research of appropriate therapies able to delay or retard their onset and progression is growing. Of particular interest is a new branch of the medical science , called anti-ageing medicine since CVD are the result of cardiovascular ageing. Senescent cells (SC) accumulate in cardiovascular system contributing to the onset of typical age-related cardiovascular conditions (i.e., atherosclerosis, medial aorta degeneration, vascular remodeling, stiffness). Such conditions progress in cardiovascular pathologies (i.e., heart failure, coronary artery disease, myocardial infarction, and aneurysms) by evocating the production of a proinflammatory and profibrotic senescence-associated secretory phenotype (SASP). Consequently, therapies able to specifically eliminate SC are in developing. The senotherapeutics represents an emerging anti-SC treatment, and comprises three therapeutic approaches: (a) molecules to selectively kill SC, defined senolytics ; (b) compounds able in reducing evocated SC SASP, acting hence as SASP suppressors, or capable to change the senescent phenotype, called senomorphics ; (c) inhibition of increase of the number of SC in the tissues. Here, it describes them and the emerging data about current investigations on their potential clinical application in CVD, stressing benefits and limitations, and suggesting potential solutions for applying them in near future as effective anti-CVD treatments.

Translation of Cellular Senescence to Novel Therapeutics: Insights From Alternative Tools and Models

“…Lastly, senotherapeutic approaches have been used in the treatment of various age-related diseases including CVD in the last couple of years ( Anderson et al, 2019 ; Walaszczyk et al, 2019 ) and new methods are in the process ( Balistreri et al, 2021 ). Although many mechanism-based approaches for targeting senescent cells have been validated, their side effects are likely to limit therapeutic use.…”

Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy

“…This new approach would allow reconstituting aged adipose tissue by rejuvenating existing cells or by injecting their angiogenic cell products into ischemic tissue [39] . An alternative approach is to eliminate senescent cells through "senolytic" therapies [40,41] . Table 3 summarizes the main senotherapeutics in aging-associated cardiovascular diseases.…”

Senescence in Vascular Smooth Muscle Cells and Atherosclerosis

“…The suitability and reliability of traditional markers of senescence have recently been questioned due to a lack of specificity and application across cell types ( 9 – 11 ). Further, existing anti-aging drugs have limitations in their application during atherosclerosis treatment ( 12 ). To address these issues in this review, we: (1) attempt to summarize the characteristics of VSMCs senescence during the atherosclerosis process; (2) identify key factors regulating VSMCs senescence; (3) assess potential pathways that may be exploited therapeutically to mitigate VSMC senescence; (4) discuss the progression of atherosclerotic cardiovascular disease, and the current challenges faced in fully characterizing this process.…”