Research Progress in Clearance of Senescent Cells in Aging and Age-related Diseases

Aging is an emerging and important research area. With the accumulation of knowledge in related fields and the advancement of technology, people gradually realized that aging itself can be intervened and it is of great scientific and practical significance to delay aging, especially delaying the occurrence and development of age-related diseases. Among the many factors that cause individual aging, the accumulation of senescent cells is considered to be an important reason that leads to organ aging and degeneration, and finally causes the age-related diseases. In recent years, a number of studies have shown that removing senescent cells in vivo can delay the occurrence of multiple age-related diseases, which directly proves that senescent cells are one of the important causes of age-related diseases, providing a new target for the treatment of age-related diseases. Cellular senescence is generally considered due to the activation of cell cycle inhibition pathway induced by accumulation of damages, and the cells permanently exit the proliferation cycle. Senescent cells undergo changes in cell morphology, transcriptional profiles, protein homeostasis, epigenome and metabolism. Moreover, senescent cells resist apoptosis and therefore accumulate in multiple organs and tissues in the body. Senescent cells secrete a number of inflammatory factors, leading to a local non-infectious inflammatory tissue microenvironment, which will cause organ function deterioration and a variety of age-related diseases. Therefore, several research groups have screened the library of small molecular compounds and found that certain compounds can selectively eliminate senescent cells by targeting pathways underpinning senescent cells' resistance to apoptosis. These small molecular compounds are called "senolytics ", denoting compounds for killing senescent cells. Senolytics have been shown to alleviate multiple age-related diseases and prolong the lifespan in animal models. Therefore, targeted killing of senescent cells has an important clinical application prospect for the treatment of a variety of age-related diseases so as to improve the healthy lifespan. In addition, strategies such as stem cell transplantation, gene editing and heterochronic parabiosis are also of great significance and inspiration in the development of anti aging research. By summarizing the recent important progress in the field of senescent cell clearance and a variety of anti-aging strategies, this paper briefly reviews the history of cellular senescence research, discusses the relationship between cellular senescence and age-related diseases, emphasizing on the potential therapeutic applications by targeting senescent cells and the limitations, as well as the further research directions in this field.