With age the immune system becomes (a) ever less capable, but also (b) ever more inflammatory and overactive. Sustained inflammation is disruptive to tissue structure and function, contributing to age-related conditions, while the growing incapacity leads to an inability to sufficiently defend against infectious pathogens, destroy senescent cells, and destroy cancerous cells. The immune system is complex, the regulation of inflammation particularly so, and there are any number of measures that to some degree reflect the aging of the immune system. Not all of them are good, different measures are better or worse in specific contexts, and there is some degree of uncertainty over the quality of any given measure.
Identifying biomarkers of aging is essential for understanding their effects on health, disease, and responses to longevity-promoting interventions. Immunological biomarkers can help differentiate between changes that are driven by aging and those specific to diseases, which is particularly important for conditions that predominantly affect the elderly.
Novel biomarkers, such as the inflammatory aging clock (iAge), leverage deep learning to quantify chronic systemic inflammation and have shown strong correlations with multimorbidity and frailty. Additionally, immune cell proportion changes have been identified as significant biomarkers of aging. Recent studies using single-cell RNA sequencing (scRNA-seq) have revealed novel shifts in immune cell compositions, highlighting the complex and dynamic nature of immune aging. Moreover, lifestyle modifications, including diet and exercise, have shown promise in improving immune aging by positively impacting immunosenescence biomarkers. Additionally, certain drug interventions, such as metformin or mTOR inhibitors, offer targeted therapeutic benefits for conditions associated with immune aging.
This review aims to update the understanding of the clinical significance of immune aging, including its phenotypic and functional changes, and model immune aging in humans. We explore novel biomarkers and their roles, as well as potential strategies for mitigating the adverse effects of immunosenescence through targeted therapies and lifestyle modifications.
Link: https://doi.org/10.1093/jimmun/vkae036
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