Physiological and pathological consequences of cellular senescence

Abstract

Cellular senescence, a permanent state of cell cycle arrest accompanied by a complex phenotype, is an essential mechanism that limits tumorigenesis and tissue damage. In physiological conditions, senescent cells can be removed by the immune system, facilitating tumor suppression and wound healing. However, as we age, senescent cells accumulate in tissues, either because an aging immune system fails to remove them, the rate of senescent cell formation is elevated, or both. If senescent cells persist in tissues, they have the potential to paradoxically promote pathological conditions. Cellular senescence is associated with an enhanced pro-survival phenotype, which most likely promotes persistence of senescent cells in vivo. This phenotype may have evolved to favor facilitation of a short-term wound healing, followed by the elimination of senescent cells by the immune system. In this review, we provide a perspective on the triggers, mechanisms and physiological as well as pathological consequences of senescent cells.

Fig. 1

Biological consequences of cellular senescence. Cellular senescence can be induced by various triggers, including, but not limited to, telomere dysfunction, oncogene activation, reactive oxygen species and cell–cell fusion. Short-term presence of senescent cells plays a beneficial role in tumor suppression, wound healing and embryonic development. However, the long-term persistence of senescent cells in tissues can paradoxically promote tumorigenesis and development of age-related diseases

Fig. 2

Identifying senescent cells. The use of several molecular markers that represent different characteristics of cell senescence is necessary for identifying senescent cells. The markers are divided into categories according to their function. A combination of markers representing different categories might increase the validity of the identification

Fig. 3

Therapeutic strategies for preventing and eliminating senescent cells. The diagram summarizes the proposed strategies to reduce the presence of senescent cells. These strategies include: extending telomere length with the use of telomerase activators would enhance the replicative lifespan of cells and prevent replicative senescence. Senescent cells could potentially be reverted/reprogrammed back to their functional state. Rejuvenation of an age-impaired immune system may enhance removal of senescent cells. Alternatively, enhancing immune recognition of senescent cells may also be an option. Therapeutic compounds can be developed which specifically target and induce cell death in senescent cells