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. 2022 May 5;77(5):883-891.
doi: 10.1093/gerona/glab330.

Age-Related Sexual Dimorphism on the Longitudinal Progression of Blood Immune Cells in BALB/cByJ Mice

Cláudia Serre-Miranda  1   2 , Susana Roque  1   2 , Palmira Barreira-Silva  1   2 , Claudia Nobrega  1   2 , Neide Vieira  1   2 , Patrício Costa  1   2 , Joana Almeida Palha  1   2 , Margarida Correia-Neves  1   2
Affiliations

Age-Related Sexual Dimorphism on the Longitudinal Progression of Blood Immune Cells in BALB/cByJ Mice

Cláudia Serre-Miranda et al. J Gerontol A Biol Sci Med Sci. .

Abstract

The study of immune system aging is of relevance, considering its myriad of interactions and role in protecting and maintaining body homeostasis. While mouse models have been extensively used to study immune system aging, little is known on how the main immune populations progress over time and what is the impact of sex. To contribute to filling this gap, male and female BALB/cByJ mice were longitudinally evaluated, from 3 to 18 months old, for the main blood populations, assessed by flow cytometry. Using linear mixed-effect models, we observed that the percentages of neutrophils, monocytes, eosinophils, and total natural killer (NK) cells increase with aging, while those of B cells, T cells (including CD4+ and CD8+ subsets), and Ly6C+ NK cells decrease. Males present higher percentages of neutrophils and classical monocytes Ly6Chigh over time, while females present higher percentages of total T cells, both CD4+ and CD8+, eosinophils, and NK cells. Males and females display similar percentages of B cells, even though with opposite accelerated progressions over time. This study revealed that mouse models recapitulate what is observed in humans during aging: an overall proportional decrease in the adaptive and an increase in the innate immune cells. Additionally, it uncovers an age-related sexual dimorphism in the proportion of immune cells in circulation, further strengthening the need to explore the impact of sex when addressing immune system aging using mouse models.

Keywords: Adaptive immune; Aging; Animal model; Blood; Gender differences; Immunosenescence; Innate immune system; Linear mixed models; Sex; system.

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Figures

Figure 1.
Figure 1.
Longitudinal evaluation of blood immune cells. Percentages of the main innate (eosinophils [A], total NK cells [B], Ly6C+ NK cells [C], neutrophils [D], and monocytes Ly6Chigh [E]) and adaptive immune cell populations over time (total B cells [F], total T cells [G], CD4+ T cells [H], CD8+ T cells [L], and activation compartments within CD4+ and CD8+ T cells: CD62L− [I and M, respectively], CD62Lhigh [J and N, respectively] and CD62Lint [K and O, respectively]). The representation combines the results of 3 independent experimental sets. Each dot represents one animal, where males are depicted as diamonds (teal in online version) and females as circles (orange in online version). Lines represent the best-fit equation representative of the data (either linear regression or second-order polynomial [quadratic] functions).
Figure 2.
Figure 2.
Variance of each immune cell population at various time points (overall—top panel; only on females—middle panel; only on males—bottom panel). Variance calculated on normalized values (z-scores). Dark grey corresponds to the lowest and highest variances (in online version blue corresponds to the lowest variances and red to the highest).
See this image and copyright information in PMC

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