Defective control of cytoplasmic calcium concentration in T lymphocytes from old mice

Cytoplasmic calcium concentration ([Ca] i ) rises within minutes of exposure of T lymphocytes to a mitogen. T cells from old mice are defective in this reaction, a defect that could reflect either altered signal transduction or instead a more general age‐associated change in intracellular calcium regulation. We therefore tested the ability of T cells from old mice to regulate their [Ca] i concentration after exposure to low concentrations of ionomycin, an agent that raises [Ca] i but bypasses receptor‐mediated signal transduction mechanisms. Exposure of T cells to ionomycin leads to an abrupt increase in [Ca] i followed by stabilization at a dose‐dependent plateau level that is affected by extracellular EGTA, by calmodulin inhibitors, and by modulators of protein kinase C. Plateau levels of [Ca] i after ionomycin challenge were consistently lower in T cells from old mice than in T cells from young mice. Flow cytometric experiments showed that while essentially all T cells from both old and young mice responded to ionomycin, they did so to an extent that depended on donor age. The age‐dependent increase in resistance to ionomycin‐induced changes in [Ca] i cannot be attributed to diminished membrane permeability to the ionomycin‐calcium complex. The data suggest that aging may lead, in T lymphocytes, to a relative resistance to increases in [Ca] i , a resistance that in turn prevents cell activation.