Aging and Alzheimer disease lead to alterations in several biochemical properties of cultured skin fibroblasts. Total bound calcium increases in fibroblasts due to normal aging (+52%) and is elevated even further with Alzheimer disease (+197%). Processes that require mitochondrial function, such as glucose and glutamine oxidation, declined in cells from aged donors (-25%) and decreased even further in Alzheimer disease (-46%). In addition, biosynthetic processes that depend upon mitochondrial function, such as glucose or glutamine incorporation into protein and lipid, paralleled the oxidative decreases. Cytosolic and nuclear processes such as leucine incorporation into protein and thymidine into DNA were depressed more by aging than Alzheimer disease. These findings suggest that calcium homeostasis and mitochondrial functions are altered more by Alzheimer disease than normal aging.