Cellular senescence: mechanisms and clinical implications

• Anna M. Masyutina
• Mikhail V. Pashenkov
• Boris V. Pinegin

Abstract

Cellular senescence is a fundamental biological process which consists of an irreversible blocking of cell division induced by extrinsic or intrinsic factors. Cellular senescence is required for development and maintenance of normal structure of tissues and organs as well as for prevention of malignant transformation. However, in an aged organism, accumulation of senescent cells in tissues becomes an important factor contributing to tissue damage and aging-associated diseases. Negative effects of senescent cells are mediated by secretion of pro-inflammatory cytokines in the context of the so-called senescence-associated secretory phenotype (SASP). In immune system, increased numbers of senescent cells contribute to generalization of tissue damage and compromises defense against pathogens. In experimental models, elimination of senescent cells results in delayed development of aging-associated pathologies, increases life span of animals. Senotherapeutic drugs, designed to treat age-associated diseases by eliminating senescent cells or modulating SASP, are a subject of intense pre-clinical and clinical research.

Keywords:cellular senescence; senescent cells; immunosenescence; T cells; cytokines; senotherapeutics

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