Anti-senescence therapies: a new concept to address cardiovascular disease

Accumulation of senescent cells is an increasingly recognized factor in the development and progression of cardiovascular disease. Senescent cells of different types display a pro-inflammatory and matrix remodeling molecular program, known as the 'senescence associated secretory phenotype' (SASP), which has roots in (epi)genetic changes. Multiple therapeutic options (senolytics, anti-SASP senomorphics and epigenetic reprogramming) that delete or ameliorate cellular senescence have recently emerged. Some drugs routinely used in the clinics also have anti-senescence effects. However, multiple challenges hinder the application of novel anti-senescence therapeutics in the clinical setting. Understanding the biology of cellular senescence, advantages and pitfalls of anti-senescence treatments, as well as patients that can profit from these interventions is necessary to introduce this novel therapeutic modality into the clinics. We provide a guide through the molecular machinery of senescent cells, systematize anti-senescence treatments and propose a pathway towards senescence-adapted clinical trial design to aid future efforts.