Deficient Ca2+ signaling and metabolic activity in Aged T cells – Are they connected?

The immune system is compromised in aged individuals, characterized by loss of adaptive immunity and an increase in non-specific innate immunity. Amongst the immune system components most affected by aging are the T lymphocytes. T-cell activation significantly increases intracellular calcium (Ca2+) concentration, an important secondary messenger that regulates multiple cellular functions, including proliferation, differentiation, and cytokine secretion. Calcium influx in T cells depends on glycolysis, as phosphoenolpyruvate (PEP), a glycolytic intermediate, inhibits Sarco/ER Ca2+-ATPase (SERCA) to induce store-operated calcium entry (SOCE). With aging Ca2+ homeostasis is often dysregulated, leading to blunted Ca2+ signaling. Moreover, in aged T cells, activation-induced metabolic reprogramming is deficient. This study investigated whether deficient metabolic activity in aged T cells was connected to dysregulates Ca2+ entry.