2025/09/12 by Mohammed Ayoub, Marc Ayoub, Chris Abou Jaoude +4
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Genetics, Aging, and Longevity in Model Organisms #Neuroinflammation and Neurodegeneration Mechanisms #Tryptophan and brain disorders
paper · doi:10.1111/imm.70036
crossref issued 2025/09/12 · crossref published 2025/09/12 · crossref published-online 2025/09/12 · openalex publication_date 2025/09/12 · crossref created 2025/09/12 · openalex created_date 2025/10/10 · crossref deposited 2025/12/01 · crossref published-print 2026/01/01 · crossref indexed 2026/07/30 · openalex updated_date 2026/07/30
Immunosenescence is the process of immune dysfunction and gradual deterioration of the immune system associated with aging, while cellular senescence is the stable cell cycle arrest that can occur in non-immune or immune cells in response to stress or damage. Immunosenescence significantly impacts both the innate and adaptive immune responses and is characterised by physical changes in lymphoid organs, as well as dysfunctions in cellular and molecular mechanisms. Key features of immunosenescence include T-cell dysfunction, thymic involution, B cell aging, an imbalance in the ratio of naïve to memory cells, chronic inflammation known as inflammaging and metabolic dysregulation. This decline in immune cell diversity and functionality contributes to various age-related diseases. Therefore, restoring a more 'juvenile' immune function in aging populations, through interventions targeting immunosenescence, holds promise for alleviating many age-related diseases and promoting healthier aging. In this review, we provide a comprehensive understanding of the interplay between the immune system and senescent cells in both healthy and disease contexts. We then dissect the immune dysfunction that occurs with aging, known as immunosenescence, and explore its impact on the health of elderly individuals. Finally, we discuss recent advances in targeting immune system aging to promote healthier longevity, with a special focus on Programmed Death-Ligand 1 (PD-L1), an emerging and promising target for therapeutic intervention.