Jing Luan
Bryan Wu
Xingchun Gao- 1Clinical Research Center, The 924th Hospital of the Chinese People’s Liberation Army Joint Logistic Support Force, Guilin, Guangxi, China
- 2Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, Shaanxi, China
- 3Roche (United States), Pleasanton, CA, United States
- 4Institute of Basic Medical Sciences, School of Basic Medical Science, Xi’an Medical University, Xi’an, Shaanxi, China
Editorial on the Research Topic
Immune senescence: a key driver of aging and age-related disorders
Aging is a multifaceted biological process characterized by progressive declines in physiological function, increasing susceptibility to diseases such as cancer, infections, autoimmune disorders, and metabolic syndromes (Ajoolabady et al., 2024; Guo et al., 2022). A growing body of evidence underscores the critical role of immunosenescence—the age-related functional deterioration of the immune system—in mediating these vulnerabilities. Immunosenescence disrupts immune surveillance, diminishes vaccine efficacy, elevates cancer risk, and fosters a state of chronic, low-grade inflammation termed “inflammaging” (Doherty et al., 2025; Franck et al., 2025; Liu et al., 2023). While traditionally viewed as an inevitable aspect of chronological aging, accumulating data reveal significant interindividual variability in immunosenescence trajectories, shaped by genetic predisposition, lifestyle factors, and environmental exposures (Wang et al., 2022). This heterogeneity underscores the urgent need to identify reliable biomarkers of immune aging and clarify the mechanisms linking immunosenescence to systemic aging and specific pathologies. Accordingly, these efforts—elucidating these mechanisms and tracking the process via biomarkers—are pivotal for developing targeted strategies to modulate immune function, ultimately mitigating age-related decline and extending health span (Ross et al., 2024).
These four articles within this Research Topic collectively enhance our understanding of immunosenescence, emphasizing its extensive impact on health and disease. Ge et al. reveal significant heterogeneity in lymphocyte subsets between infants and older adults, demonstrating that infants possess higher absolute counts of naïve and memory T cells, while older adults exhibit increased levels of NK cells. Furthermore, the age-related polarization of the CD4+/CD8+ ratio emerges as a promising biomarker for immunosenescence, offering critical insights to inform age-specific vaccination strategies and immune risk stratification in elderly populations. This shift not only reflects the progressive decline in naive T-cell reserves but also highlights the accumulation of terminally differentiated lymphocytes, which together underscore the systemic dysregulation characteristic of aging immune systems. Building on this, Zhang et al. establish a direct connection between cellular senescence and the pathogenesis of Crohn’s disease (CD), identifying senescence-related gene signatures and key hub genes such as STAT3, IL6, and IL1A that contribute to immune dysregulation and intestinal pathology. By elucidating senescence-related gene signatures that delineate molecular subtypes and correlate with immune dysregulation, their research effectively bridges fundamental aging biology with complex chronic inflammatory disorders. Lu et al. demonstrate the clinical utility of a simple systemic immune-inflammation index (SII), derived from routine blood counts, as a robust predictor of all-cause and cancer-specific mortality in older adults (≥60 years). This work underscores the translational potential of simple, inflammation-associated metrics in stratifying mortality risk. Finally, Trebing et al. address a vital methodological consideration in immune aging research by investigating the stability of a composite immune age metric (IMMAX) across the circadian cycle. Their findings validate IMMAX as a reliable biomarker while highlighting the need for standardized sampling timing in immune aging studies. Together, these studies affirm that immunosenescence is not merely a consequence of aging but an active contributor to its pathology, influencing disease susceptibility, progression, and outcomes across diverse contexts.
In summary, the convergence of evidence from these studies solidifies immunosenescence as a fundamental aspect of aging biology. The dynamic interplay between cellular senescence, inflammatory pathways, and circadian rhythms elucidated here presents novel opportunities for biomarker development and therapeutic targeting. Future research should prioritize longitudinal studies to unravel causal relationships between immune aging and systemic decline while leveraging omics technologies to identify precision interventions. By harnessing insights from immunosenescence, we can aspire not only to extend healthspan but also to redefine aging as a modifiable process—ultimately transforming our approach to age-related diseases.
Author contributions
JL: Writing – original draft. BW: Writing – original draft. XG: Supervision, Writing – review and editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. This work is supported by the Scientific Research Program Funded by Education Department of Shaanxi Provincial Government (No.23JS049), Natural Science Basic Research Program of Shaanxi (2020JZ-56), Program for Science and Technology Innovation Team in Xi’an Medical University (2021TD05), Shaanxi Youth Talents Project, Social Development Project of Shaanxi Provincial Science and Technology Department (2025SF-YBXM-377).
Conflict of interest
Author BW was employed by Roche (United States).
The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
Ajoolabady, A., Pratico, D., Tang, D., Zhou, S., Franceschi, C., and Ren, J. (2024). Immunosenescence and inflammaging: mechanisms and role in diseases. Ageing Res. Rev. 101, 102540. doi:10.1016/j.arr.2024.102540
Doherty, T. M., Weinberger, B., Didierlaurent, A., and Lambert, P. H. (2025). Age-related changes in the immune system and challenges for the development of age-specific vaccines. Ann. Med. 57, 2477300. doi:10.1080/07853890.2025.2477300
Franck, M., Tanner, K. T., Tennyson, R. L., Daunizeau, C., Ferrucci, L., Bandinelli, S., et al. (2025). Nonuniversality of inflammaging across human populations. Nat. Aging 5, 1471–1480. doi:10.1038/s43587-025-00888-0
Guo, J., Huang, X., Dou, L., Yan, M., Shen, T., Tang, W., et al. (2022). Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct. Target Ther. 7 (7), 391. doi:10.1038/s41392-022-01251-0
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., et al. (2023). Immunosenescence: molecular mechanisms and diseases. Signal Transduct. Target Ther. 8 (8), 200. doi:10.1038/s41392-023-01451-2
Ross, J. B., Myers, L. M., Noh, J. J., Collins, M. M., Carmody, A. B., Messer, R. J., et al. (2024). Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity. Nat. Apr 628, 162–170. doi:10.1038/s41586-024-07238-x
Keywords: aging, biomarker, circadian, Crohn’s disease, immune cell, immune senescence
Citation: Luan J, Wu B and Gao X (2026) Editorial: Immune senescence: a key driver of aging and age-related disorders. Front. Aging 7:1776990. doi: 10.3389/fragi.2026.1776990
Received: 29 December 2025; Accepted: 02 January 2026;
Published: 13 January 2026.
Edited and reviewed by:
Anshu Agrawal, University of California, Irvine, United StatesCopyright © 2026 Luan, Wu and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xingchun Gao, Z3hjMTk5MjgxMDAzQDE2My5jb20=