Abstract: Immunosenescence is a critical driver of systemic aging and affects infection susceptibility, vaccine responsiveness, and tumor immune surveillance in elderly individuals. This review aims to summarize the multilevel remodeling of the aging immune system and its effects in age-related diseases. A key feature of immunosenescence is the coexistence of impaired adaptive immunity and enhanced chronic inflammation. Aging of bone marrow and thymic involution lead to disturbed lymphoid-myeloid balance of hematopoietic stem cells and diminished naïve T cell output. Aging of secondary lymphoid organs further impair naïve T cell and B cell maintenance, antigen presentation, T-B cell interaction, and germinal center formation, leading to reduced antigen-specific responses to emerging infections and antigens. Meanwhile, aged innate immune cells show impaired phagocytosis and clearance, resulting in the accumulation of senescent cells, cell debris, and damage-associated molecular patterns. These signals activate downstream pro-inflammatory pathways and promote cytokine release. Persistent inflammation further aggravates immune-cell dysfunction and tissue microenvironmental damage, forming a vicious cycle of inflammaging. Therefore, declined adaptive immunity and inflammaging disrupt immune homeostasis and contribute to the development and progress of multiple age-related diseases, including cardiovascular, neurodegenerative, and autoimmune diseases. Future efforts should focus on precisely deciphering systemic immunosenescence, from central lymphoid organs to peripheral tissues, and on developing targeted intervention strategies based on the critical regulatory nodes in the aging of immune system.