Senolytic Vaccines from the Central and Peripheral Tolerance Perspective

Preventive medicine has proven its long-term effectiveness and economic feasibility. Over the last century, vaccination has saved more lives than any other medical technology. At present, preventative measures against most infectious diseases are successfully used worldwide; in addition, vaccination platforms against oncological and even autoimmune diseases are being actively developed. At the same time, the development of medicine led to an increase in both life expectancy and the proportion of age-associated diseases, which pose a heavy socio-economic burden. In this context, the development of vaccine-based approaches for the prevention or treatment of age-related diseases opens up broad prospects for extending the period of active longevity and has high economic potential. It is well known that the development of age-related diseases is associated with the accumulation of senescent cells in various organs and tissues. It has been demonstrated that the elimination of such cells leads to the restoration of functions, rejuvenation, and extension of the lives of experimental animals. However, the development of vaccines against senescent cells is complicated by their antigenic heterogeneity and the lack of a unique marker. In addition, senescent cells are the body's own cells, which may be the reason for their low immunogenicity. This mini-review discusses the mechanisms of central and peripheral tolerance that may influence the formation of an anti-senescent immune response and be responsible for the accumulation of senescent cells with age.