Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation
5 affiliations
- 1Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham , ,
- 2Laboratory of Exercise Physiology (FISEX), University of Campinas , ,
- 3Department of Kinesiology, School of Health and Human Sciences, University of North Carolina Greensboro , , ,
- 4Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health , ,
- 5National Institute for Health and Care Research (NIHR), Biomedical Research Centre , ,
Abstract
Background: Ageing impairs T cell function and responses to vaccines and infections. Effective T cell function requires rapid metabolic switching towards glycolysis, which becomes dysregulated with age. We have shown that physically active older adults have T cells that are more functional and metabolically fit. As exercise acutely elevates adrenaline and mobilises T cells via β2-adrenergic receptors (β2-AR), we hypothesise that habitual physical activity (PA) preserves β2-AR-mediated metabolic stimulation in T cells from older adults.
Methods: Older adults (≥65 years) with habitually high PA (HPA, n = 6) or habitually moderate PA (MPA, n = 6) were compared with young controls (18–35 years, n = 6). T cells were exposed to the β-agonist isoproterenol for 30 min to mimic acute exercise-like adrenergic stimulation, with or without the β2-AR blocker ICI-118,551. Following 1 h of rest, T cells were stimulated for 4 h in vitro with PMA and ionomycin. T cell activation (CD69), glucose transporter-1 (Glut1), intracellular cAMP concentrations under isoproterenol stimulation, and β2-AR mRNA expression were assessed.
Results: Older adults exhibited impaired CD8+ T cell activation and β2-AR blockade inhibited activation in all groups. Glut1 expression in CD8+ T cells was higher in older MPA than young, but did not differ from older HPA. In CD8+ T cells that were not stimulated with PMA and ionomycin, β2-AR blockade (with β-AR stimulation) increased Glut1 expression in all groups compared with β-AR stimulation alone, and this increase was greater in older HPA than MPA (p = 0.043). No group differences were observed in β2-AR mRNA expression or isoproterenol-induced β-AR cAMP responsiveness.
Conclusion: These exploratory findings indicate that individuals with higher levels of habitual PA have lower age-associated impairments in CD8+ T cell activation and metabolic switching in response to β stimulation. Interestingly, β2-AR blockade did not fully abrogate β stimulation, therefore future studies should investigate a potential influence of β1-AR in this modulation, to generate definitive conclusions.
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BibTeX
@article{sardeli2026impact,
title = {{Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation}},
author = {Amanda V. Sardeli and Ana Ramkrapes and Jakob Boyes-Jensen and Jon Hazeldine and Helena Batatinha and Niharika A. Duggal and Davide Calebiro and James E. Turner},
journal = {Frontiers in aging},
year = {2026},
month = oct,
doi = {10.3389/fragi.2026.1869552},
url = {https://europepmc.org/article/PMC/PMC13727592},
note = {CC BY},
}
RIS
TY - JOUR
TI - Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation
AU - Amanda V. Sardeli
AU - Ana Ramkrapes
AU - Jakob Boyes-Jensen
AU - Jon Hazeldine
AU - Helena Batatinha
AU - Niharika A. Duggal
AU - Davide Calebiro
AU - James E. Turner
PY - 2026
DA - 2026/10/20
JO - Frontiers in aging
DO - 10.3389/fragi.2026.1869552
UR - https://europepmc.org/article/PMC/PMC13727592
AB - Background: Ageing impairs T cell function and responses to vaccines and infections. Effective T cell function requires rapid metabolic switching towards glycolysis, which becomes dysregulated with age. We have shown that physically active older adults have T cells that are more functional and metabolically fit. As exercise acutely elevates adrenaline and mobilises T cells via β2-adrenergic receptors (β2-AR), we hypothesise that habitual physical activity (PA) preserves β2-AR-mediated metabolic stimulation in T cells from older adults. Methods: Older adults (≥65 years) with habitually high PA (HPA, n = 6) or habitually moderate PA (MPA, n = 6) were compared with young controls (18–35 years, n = 6). T cells were exposed to the β-agonist isoproterenol for 30 min to mimic acute exercise-like adrenergic stimulation, with or without the β2-AR blocker ICI-118,551. Following 1 h of rest, T cells were stimulated for 4 h in vitro with PMA and ionomycin. T cell activation (CD69), glucose transporter-1 (Glut1), intracellular cAMP concentrations under isoproterenol stimulation, and β2-AR mRNA expression were assessed. Results: Older adults exhibited impaired CD8+ T cell activation and β2-AR blockade inhibited activation in all groups. Glut1 expression in CD8+ T cells was higher in older MPA than young, but did not differ from older HPA. In CD8+ T cells that were not stimulated with PMA and ionomycin, β2-AR blockade (with β-AR stimulation) increased Glut1 expression in all groups compared with β-AR stimulation alone, and this increase was greater in older HPA than MPA (p = 0.043). No group differences were observed in β2-AR mRNA expression or isoproterenol-induced β-AR cAMP responsiveness. Conclusion: These exploratory findings indicate that individuals with higher levels of habitual PA have lower age-associated impairments in CD8+ T cell activation and metabolic switching in response to β stimulation. Interestingly, β2-AR blockade did not fully abrogate β stimulation, therefore future studies should investigate a potential influence of β1-AR in this modulation, to generate definitive conclusions.
SN - 2673-6217
ER -