Fig. 2

Cellular mechanisms of immunosenescence. Aging-induced alterations in various immune cell populations are depicted with young cells in the top row and aged cells in the bottom row. (1) HSC: Aging increases the number of HSCs but weakens their function. SNS degeneration decreases ADRβ3 signaling, generating an inflammatory niche. Myeloid-biased differentiation reduces lymphoid output, weakening adaptive immunity. (2) Neutrophils: Aged neutrophils exhibit prolonged lifespan, hypersegmentation, and impaired chemotaxis but enhanced CXCL1-driven recruitment. Elevated NET formation, ROS, and TNF-α production promote chronic inflammation. (3) Macrophages and Monocytes: Aging increases the proportion of CD14⁺CD16⁺ monocytes, which exhibit a proinflammatory phenotype with increased TNF-α and IL-6 production. Reduced phagocytosis causes debris accumulation and chronic inflammation. Elevated ROS, NO, and β2M contribute to metabolic diseases and cognitive decline. (4) T cells: Aging reduces the levels of IL-7 and chemokines, impairing naïve T cell survival, proliferation, and lymph node entry and limiting renewal. Aging decreases CD8⁺ T cell diversity and number. CD160 and CD244 expression increases, resembling an exhausted phenotype. Aged CD8⁺ T cells show reduced cytotoxicity and produce less IFN-γ, granzyme B, and perforin. CD4⁺ T cell activation decreases in part due to elevated PD-1 expression. (5) Aged DCs have weaker antigen presentation (MHC/CD40 downregulation), resulting in weaker CD4⁺ T cell responses. (6) NK cells: Aging reduces the number of CD56^bright NK cells and their activating receptors while increasing the number of inhibitory receptors (KIRs), impairing cytotoxicity. Degranulation and perforin secretion decline. NK cells shift toward a CD56^dim subset, where they secrete more proinflammatory cytokines, contributing to chronic inflammation. (7) B cells: In elderly individuals, antibody production and class switching decline due to CD40 downregulation and weakened BCR signaling. ABC expansion disrupts immune balance, weakening humoral immunity