Considering Cellular Senescence in Macrophages – Fight Aging!


Cells become senescent in response to damage, a toxic environment, the signaling of nearby senescent cells, or, most commonly, because they reach the Hayflick limit on replication. Senescent cells cease replication and begin to secrete pro-inflammatory signals, attracting the attention of the immune system. With advancing age he aged immune system becomes less able to clear senescent cells in a timely manner, leading to a growing, permanent presence of senescent cells in tissues. Some of these senescent cells are themselves immune cells. Given the importance of the immune system to tissue maintenance and regeneration, particularly tissue residence innate immune cells such as macrophages, it should be no surprise to find that senescence in these cells is viewed as contributing to degenerative aging.

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. As the first-responder to the pathogens and damage in the immune response, macrophages play a vital role in the function of phagocytosis and polarization towards different situations to mediate the inflammation inside individuals. Senescent macrophages are usually featured with an unbalanced polarization state, compromised phagocytosis, impaired migration, and damaged autophagy. Due to the abnormal accumulation and the aberrant functions of senescent macrophages, aged people tend to be unhealthy or with acerbated diseases.

Senescent macrophages play various functions in different diseases or organs which indicates that treatments should be specialized for the distinctive characteristics of senescent macrophages. In the cognitive decline, senescent macrophages turn to behave abnormally in phagocytosis for the dampened scavenging of abnormal unfolded proteins in the central nervous system. The imbalanced polarization state in senescent macrophages also contributes to the development of malignant cancers. More senescent macrophages tend to the M2 phenotype promoting tumor cells proliferating and counteract against cytotoxic T lymphocytes.

Contrarily, in ovarian tissue, senescent macrophages turn to the M1 phenotype with a higher level of iNOS which causes ovarian aging. Secretions of senescent macrophages are also in close relationship with some organ disorders. Grancalcin produced by senescent macrophages would exacerbate skeletal aging for the impaired balance between osteogenesis and adipogenesis of bone marrow stroma cells. Additionally, metabolic disturbances like chaotic cholesterol levels in senescent macrophages cause age-related macular degeneration for their proangiogenic function.



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