Senescent Cells and Antiaging Medicine: Senescent Cells and Senescence-Associated Secretory Phenomenon (SASP)

Cellular senescence is an irreversible cell proliferation stop induced when strong DNA damage occurs, and the cell cycle checkpoint mechanism is strongly activated. This can be considered an important cancer suppression mechanism, along with apoptosis, to prevent the increase of abnormal cells inherent in normal cells. However, unlike apoptosis, which is cell death, it is known that cells that have undergone senescence are resistant to apoptosis and continue to survive for a long time. From these long-lived senescent cells, it has been revealed that various secretory proteins such as inflammatory cytokines, chemokines, extracellular matrix remodeling factors, and growth factors are produced. This phenomenon is called the senescence-associated secretory phenotype (SASP) [1]. The effects of SASP factors are diverse. At the cellular level, SASP factors work paracrinally on surrounding cells, causing them to age, or autocrinally on the senescent cells themselves, further enhancing senescence [1]. At the individual level, it has been reported that immune cells that have migrated due to SASP factors secreted from senescent hepatic stellate cells help to remove accumulated senescent cells [2, 3]. Also, as an important physiological action of SASP, it is known that SASP that occurs transiently in fibroblasts during tissue damage works for tissue repair. On the other hand, adverse effects have also been suggested. SASP in aging individuals where senescent cells accumulate is thought to lead to age-related inflammatory diseases and functional decline. Even in cancer-associated fibroblasts (CAFs) in the microenvironment of cancer tissues, senescence and SASP are observed [1], and it is known to promote cancer. Although the action of SASP is complex, there is a tendency for it to become a disadvantageous pathological action when SASP does not converge and persists (Fig. 24.1).