INS and diabetes mellitus: Given that Ca2+ dysregulation is considered a hallmark of brain aging [65], [78], [79], [80], is present in animal models of diabetes [81], [82], [83], [84], and appears to contribute to insulin resistance in the periphery [85], we tested the hypothesis that PIO might reduce Ca2+-dependent brain biomarkers of aging in vivo and thereby provide some relief from the cognitive decline seen with aging.