Work

Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation

Year: 2026

Type: article

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 β 2 -adrenergic receptors (β 2 -AR), we hypothesise that habitual physical activity (PA) preserves β 2 -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 β 2 -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 β 2 -AR mRNA expression were assessed. Results Older adults exhibited impaired CD8 + T cell activation and β 2 -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, β 2 -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 β 2 -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, β 2 -AR blockade did not fully abrogate β stimulation, therefore future studies should investigate a potential influence of β 1 -AR in this modulation, to generate definitive conclusions.

Source: Frontiers in Aging

DOI: 10.3389/fragi.2026.1869552