Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 May 1;214(5):889-902.
doi: 10.1093/jimmun/vkae036.

Immunological biomarkers of aging

Fei Wu  1 , Wei-Chieh Mu  1 , Nikola T Markov  1 , Matias Fuentealba  1 , Heather Halaweh  1 , Fiona Senchyna  1 , Max N Manwaring-Mueller  1 , Daniel A Winer  2   3   4   5 , David Furman  1   6
Affiliations
Review

Immunological biomarkers of aging

Fei Wu et al. J Immunol. .

Abstract

The immune system has long been recognized for its critical role in the elimination of pathogens and the development of autoimmune diseases, but recent evidence demonstrates that it also contributes to noncommunicable diseases associated with biological aging processes, such as cancer, cardiovascular disease, neurodegeneration, and frailty. This review examines immunological biomarkers of aging, focusing on how the immune system evolves with age and its impact on health and disease. It discusses the historical development of immunological assessments, technological advancements, and the creation of novel biomarkers and models to study immune aging. We also explore the clinical implications of immune aging, such as increased susceptibility to infectious diseases, poor vaccine responses, and a higher incidence of noncommunicable diseases. In summary, we provide a comprehensive overview of current research, highlight the clinical relevance of immune aging, and identify gaps in knowledge that require further investigation.

Keywords: biomarkers; human aging; immune aging; immunosenescence; inflammaging.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
A schematic representation of novel immunological biomarkers of aging. This figure illustrates advanced techniques for modeling immune aging in humans, highlighting the cellular and molecular changes in the immune system that occur with aging. It also demonstrates the phenotypic and functional consequences of these changes, such as increased susceptibility to infections and noncommunicable diseases. AD, Alzheimer’s disease; CVD, cardiovascular disease; DNAm, DNA methylation; RA, rheumatoid arthritis; T2D, type 2 diabetes; UTI, urinary tract infection.
Figure 2.
Figure 2.
A platform for modeling immune aging in humans using human tonsil-derived organoids or PBMCs. This system employs accelerated aging perturbations, such as microgravity, to simulate immune aging. Subsequent omics analyses, including RNA sequencing, are conducted to identify potential interventions that can mitigate the detrimental effects of aging on the immune system. KO, knockout.
See this image and copyright information in PMC

References

    1. Herzog CMS et al.; C. Biomarkers of Aging. Challenges and recommendations for the translation of biomarkers of aging. Nat Aging. 2024;4:1372–1383. - PubMed
    1. Wang Y, Dong C, Han Y, Gu Z, Sun C. Immunosenescence, aging and successful aging. Front Immunol. 2022;13:942796. - PMC - PubMed
    1. Furman D et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25:1822–1832. - PMC - PubMed
    1. Sayed N et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat Aging. 2021;1:598–615. - PMC - PubMed
    1. Tomusiak A et al. Development of an epigenetic clock resistant to changes in immune cell composition. Commun Biol. 2024;7:934. - PMC - PubMed