Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice

TL;DR

The study found that immune cell cytokine profiles in the peritoneum of mice are linked to lifespan, with long-lived mice showing specific immune adaptations.

Contribution

This work identifies specific immune cell cytokine patterns in peritoneal leukocytes that correlate with longevity in aging female mice.

Findings

Long-lived mice show adult-like immune profiles with specific pro- and anti-inflammatory cytokine adaptations.

Older mice with higher CD4/CD8 ratios and certain cytokine levels tend to live longer.

Negative correlations exist between specific immune cell markers and shorter lifespans.

Abstract

Peritoneal immune cell function is a reliable indicator of aging and longevity in mice and inflammaging is associated with a shorter lifespan. Nevertheless, it is unknown if the content of cytokines in these immune cells is linked to individual differences in lifespan. Therefore, this work aimed to investigate different peritoneal leukocyte populations and their content in intracellular pro-inflammatory (TNF and IL-6) and anti-inflammatory (IL-10) cytokines by flow cytometry in adult (10 months-old, n = 8) and old (18 months-old, n = 20) female Swiss/ICR mice. In addition, old mice were monitored longitudinally throughout their aging process, and the same markers were analyzed at the very old (24 months-old, n = 8) and long-lived (30 months-old, n = 4) ages. The longitudinal follow-up allowed us to relate the investigated parameters to individual lifespans. The results show that long-lived female mice exhibit an adult-like profile in most parameters investigated but also display specific immune adaptations, such as increased CD4+ and CD8+ T cells containing the pro-inflammatory TNF cytokine and CD4+ T cells and macrophages containing the anti-inflammatory cytokine IL-10. These adaptations may underlie their exceptional longevity. In addition, a negative correlation was obtained between the percentage of cytotoxic T cells, KLRG-1/CD4, large peritoneal macrophages, and the percentage of CD4+ T cells containing IL-6 and macrophages containing IL-10 in old age and lifespan, whereas a positive correlation was found between the CD4/CD8 ratio and the longevity of the animals at the same age. These results highlight the crucial role of peritoneal leukocytes in inflammaging and longevity.

The online version contains supplementary material available at 10.1007/s10522-024-10110-0.

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