Calcineurin links Ca2+ dysregulation with brain aging

Brain aging is associated with altered Ca2+ regulation. However, many Ca2signal transduction mechanisms have not been explored in the aged brain. He re, we report that cytosolic expression and activity of the Ca2+-dependent protein phosphatase calcineurin (CaN) increases in the hippocampus during a ging. CaN changes were paralleled by increased activation, but not expressi on, of CaN-regulated protein phosphatase 1 and a reduction in the phosphory lation state of CaN substrates involved in cell survival (i.e., Bcl-2-assoc iated death protein and cAMP response element-binding protein). The age-rel ated increase in CaN activity was not attributable to the inability of CaN to translocate to the membrane and was reduced by blocking L-type Ca2+ chan nels. Finally, increased CaN activity correlated with memory function as me asured with the Morris water escape task. The results suggest that altered regulation of CaN is one of the processes that could link Ca2+ dyshomeostas is to age-related changes in neural function and cognition.