The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease

Sep 12, 2025Immunology

How the Immune System and Aging Cells Interact in Aging and Disease

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Abstract

Immunosenescence is characterized by key features such as T-cell dysfunction and chronic inflammation, which may contribute to age-related diseases.

Immunosenescence involves a decline in immune cell diversity and functionality associated with aging.
Physical changes in lymphoid organs and dysfunction in cellular mechanisms are observed with immunosenescence.
Key features include thymic involution, B cell aging, and an imbalance in naïve versus memory cells.
Chronic inflammation, termed inflammaging, is linked to immunosenescence.
Targeting immunosenescence through interventions may help alleviate age-related diseases and promote healthier aging.

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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.

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The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease

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