Reviewing the Characterization of Cellular Senescence in Aging
The accumulation of senescent cells with age is an important contributing cause of age-related disease and eventual mortality. These errant cells secrete a potent mix of pro-growth, pro-inflammatory signals that disrupt normal tissue maintenance and change cell behavior for the worse, leading to structural changes and loss of organ function throughout the body. Damping senescent cell signaling, such as by selectively destroying senescent cells, has shown considerable promise as a basis for rejuvenation therapies, and the sooner that the existing approaches are widely adopted for use by the elderly population, the better.
An increase in life expectancy in developed countries has led to an insurgency of chronic aging-related diseases. In the last few decades, several studies provided evidence of the prominent role of cellular senescence in many of these pathologies. Key traits of senescent cells include cell cycle arrest, apoptosis resistance, and secretome shift to senescence-associated secretory phenotype (SASP) resulting in increased secretion of various intermediate bioactive factors important for senescence pathophysiology. However, cellular senescence is a highly phenotypically heterogeneous process, hindering the discovery of totally specific and accurate biomarkers.
Strategies to prevent the pathological effect of senescent cell accumulation during aging by impairing senescence onset or promoting senescent cell clearance have shown great potential during in vivo studies and some are already in early stages of clinical translation. The adaptability of these senotherapeutic approaches to human application has been questioned due to the lack of proper senescence targeting and senescence involvement in important physiological functions. In this review, we explore the heterogeneous phenotype of senescent cells and its influence on the expression of biomarkers currently used for senescence detection. We also discuss the current evidence regarding the efficacy, reliability, development stage, and potential for human applicability of the main existing senotherapeutic strategies.