# Immunosenescence and its impact on ischemic stroke risk and outcomes in older adults: a systematic review

**Authors:** Celest Wen Ting Seah, Matthias Ho, Collin Chu, Karishma Sachaphibulkij, Paul A. MacAry, Laura McCulloch, Velda Xinying Han, Benjamin Yong-Qiang Tan, Vanda Wen Teng Ho

PMC · DOI: 10.3389/fnagi.2026.1776458 · Frontiers in Aging Neuroscience · 2026-03-09

## TL;DR

This paper reviews how aging-related immune decline worsens stroke outcomes in older adults and suggests targeting specific immune markers could improve recovery.

## Contribution

The study systematically links immunosenescence with ischemic stroke outcomes and identifies potential therapeutic immune targets in older adults.

## Key findings

- Elevated IL-6, hs-CRP, and Th17 cells are associated with worse stroke outcomes in older adults.
- An imbalance between Th17 cells and Treg cells is observed post-stroke.
- Higher NLR and B-cell subset changes contribute to inflammation and poor recovery.

## Abstract

Age is a major risk factor for ischemic stroke (IS), with immunosenescence–age-related immune system dysfunction - contributing to worse outcomes. Immunosenescence impairs immune responses, heightens inflammation, and increases susceptibility to infections, all of which affect stroke prognosis. This review investigates the association between immunosenescence, immune cell dysfunction, and IS risk and outcomes.

A systematic review was conducted to identify cohort studies examining immunosenescence in IS patients aged 60 and above. Databases PubMed and Embase were searched up to 10 August 2024. Studies were included if they analyzed immune cell markers or inflammatory markers in relation to IS risk or outcomes. A total of 11 studies met the inclusion criteria.

Elevated inflammatory markers such as interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and Th17 cells were significantly associated with poorer stroke outcomes. Studies indicated an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Treg) post-stroke. Higher neutrophil-to-lymphocyte ratio (NLR) and alterations in B-cell subsets were also observed in older stroke patients, further contributing to the inflammatory response. These immune dysregulations were linked to increased mortality and poor recovery.

Immunosenescence plays a crucial role in IS pathogenesis and recovery, with chronic inflammation and immune dysfunction exacerbating stroke outcomes in older adults. Targeting immune markers, particularly IL-6 and the Th17/Treg imbalance, may offer new therapeutic approaches to improve stroke prognosis in aging populations. Further research is needed to develop interventions that address immunosenescence in IS.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024583142.

## Linked entities

- **Proteins:** IL6 (interleukin 6)
- **Diseases:** ischemic stroke (MONDO:1060198)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** immune (MESH:D007154), stroke (MESH:D020521), IS (MESH:D002544), immune dysregulations (OMIM:614878), inflammation (MESH:D007249)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC13006566/full.md

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Source: https://tomesphere.com/paper/PMC13006566