Abdellatif Mahmoud, Schmid Sophie T, Fuerlinger Alexander, Kroemer Guido
Department of Cardiology, Medical University of Graz, Graz 8036, Austria.
Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université Paris Cité, Sorbonne Université, Paris, France.
Cardiovasc Res. 2024 Aug 22. doi: 10.1093/cvr/cvae177.
As the global demographic landscape continues to shift towards an aged population, so does the medical and socioeconomic burden of cardiovascular diseases. Indeed, ageing is one of, if not the, key risk factor for the development of cardiovascular diseases. However, there are currently no approved cardiovascular therapeutics that primarily target the molecular and cellular mechanisms underlying the ageing process itself. In this review, we present the potential of emerging anti-ageing strategies, including epigenetic rejuvenation, metabolic reprogramming, autophagy activation, as well as senolytic and anti-inflammatory therapies, in delaying or reversing the development of age-related cardiovascular disorders, while considering potential sex differences. In doing so, we implicate cellular ageing processes in the pathogenesis of several prevalent cardiovascular diseases, such as atherosclerosis, hypertension, various types of cardiomyopathies (including its hypertrophic, ischemic, dilated, diabetic, and arrhythmogenic forms) and heart failure, particularly that with preserved ejection fraction. Finally, we outline future challenges and steps needed for the implementation of these novel anti-ageing strategies in the clinical setting, with the aim of challenging the long-held notion of ageing as a 'nonmodifiable' risk factor for cardiovascular diseases.
随着全球人口结构持续向老龄化转变,心血管疾病的医学和社会经济负担也在加重。事实上,衰老即便不是心血管疾病发展的关键风险因素,也是其中之一。然而,目前尚无获批的主要针对衰老过程本身潜在分子和细胞机制的心血管治疗方法。在本综述中,我们探讨了新兴抗衰策略的潜力,包括表观遗传年轻化、代谢重编程、自噬激活以及衰老细胞溶解和抗炎疗法,这些策略在延缓或逆转与年龄相关的心血管疾病发展方面的潜力,同时考虑了潜在的性别差异。在此过程中,我们阐述了细胞衰老过程在几种常见心血管疾病发病机制中的作用,如动脉粥样硬化、高血压、各种类型的心肌病(包括肥厚型、缺血型、扩张型、糖尿病型和致心律失常型)以及心力衰竭,尤其是射血分数保留的心力衰竭。最后,我们概述了在临床环境中实施这些新型抗衰策略所需面对的未来挑战和步骤,旨在挑战长期以来将衰老视为心血管疾病“不可改变”风险因素的观念。