Abstract Aging profoundly impacts immune function, leading to a phenomenon termed immunosenescence, characterized by diminished immune responsiveness, chronic low-grade inflammation (inflamm-aging), and increased susceptibility to infections, cancers, and autoimmune diseases. This systematic review investigates the mechanisms underpinning immunosenescence and its clinical implications, emphasizing the interplay between cellular and molecular changes and their contributions to age-related diseases. A comprehensive literature search across PubMed and Google Scholar identified studies published between 2014 and 2024. Eligible studies focused on cellular senescence, oxidative stress, chronic infections, inflamm-aging, and therapeutic strategies to mitigate immunosenescence. Data extraction and synthesis adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, with meta-analysis applied where comparable outcomes were available. Key findings include the roles of thymic involution, naive T-cell depletion, and chronic infections (e.g., cytomegalovirus and HIV) in accelerating immune aging. Mechanisms such as telomere attrition, mitochondrial dysfunction, and epigenetic modifications emerged as critical contributors. Clinically, immunosenescence impacts vaccine efficacy, chronic disease progression, and infection management in aging populations. This review underscores the need for innovative interventions targeting immune aging, including tailored vaccines, anti-inflammatory therapies, and immune rejuvenation strategies. The findings provide a foundation for future research and therapeutic advancements in managing immunosenescence-related health challenges.
Gupta et al. (Tue,) studied this question.