Senescence- and Immunity-Related Changes in the Central Nervous System: A Comprehensive Review

Abstract

Senescence is a cellular state characterized by an irreversible halt in the cell cycle, accompanied by alterations in cell morphology, function, and secretion. Senescent cells release a plethora of inflammatory and growth factors, extracellular matrix proteins, and other bioactive substances, collectively known as the senescence-associated secretory phenotype (SASP). These excreted substances serve as crucial mediators of senescent tissues, while the secretion of SASP by senescent neurons and glial cells in the central nervous system modulates the activity of immune cells. Senescent immune cells also influence the physiological activities of various cells in the central nervous system. Further, the interaction between cellular senescence and immune regulation collectively affects the physiological and pathological processes of the central nervous system. Herein, we explore the role of senescence in the physiological and pathological processes underlying embryonic development, aging, degeneration, and injury of the central nervous system, through the immune response. Further, we elucidate the role of senescence in the physiological and pathological processes of the central nervous system, proposing a new theoretical foundation for treating central nervous system diseases.

Figure 1.

The role of cellular aging in the interaction of the CNS and the immune system. The leaves represent immune cells in the immune system, and the roots represent nerve cells and glial cells in the central nervous system. The aging of the immune system and the central nervous system contribute to the aging of the other. Understanding the role of cellular aging in the immune system and the central nervous system will help to advance the research of central nervous system diseases. Created with BioRender.com.

Figure 2.

Senescence in different states of the CNS. The role of different cellular senescence, including neurons, neural stem cells, microglia, astrocytes, and oligodendrocytes, in embryonic development, aging, degeneration, injury, and neurotumor in the central nervous system is discussed in detail here. At the same time, the role of immune cell senescence in innate and adaptive immunity, including NK cell, macrophage, T cell and B cell, was discussed. Created with BioRender.com.