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.

Активность -галактозидазы, ассоциированной с сенесцентностью, в эффекторных и регуляторных Т-лимфоцитах человека

It is well established that aging is accompanied by the accumulation of senescent cells across tissues. The triggers inducing cellular senescence are diverse and vary across cell types and organs, underpinning the high diversity of senescence phenotypes within individual cell types as well as at the tissue and organismal levels. Identifying common transcriptional patterns and senescence triggers while accounting for the remarkable diversity of aged and dysfunctional cells is fundamental to developing strategies aimed at reducing senescent cell burden. The aim of this study was to investigate the heterogeneity of human senescent cells across tissues at single-cell transcriptome resolution. We selected publicly available scRNA-seq data from healthy donors for the skin, lungs, small and large intestine, kidneys, and heart. The final dataset comprised 1.5 million cells from six tissues, encompassing 64 annotated cell types across 177 donors aged 15 to 88 years. To identify cell type-specific senescence signatures, we reproduced and adapted the signature identification algorithm underlying the SenePy library. This enabled us to identify de novo genes associated with aging and senescent status within a given dataset. Next, for senescent cells of each cell type, we obtained differentially expressed gene sets and performed gene set enrichment analysis (GSEA) using a broad collection of terms reflecting functional status, metabolic activity, and adaptive responses to various forms of cellular stress. As a result, we identified organ-specific aging features in senescent cells of different cell types. We also assessed the enrichment of antigen presentation pathways and the production of senescence-associated pro-inflammatory factors (SASP) in senescent cells across tissues. Furthermore, our analysis revealed novel tissue-specific patterns of ligand-receptor interactions between senescent cells and their microenvironment.