This review by Naftali Raz and Karen M. Rodrigue explores the patterns and biological underpinnings of cognitive and behavioral changes throughout adulthood, focusing on brain structure. The authors summarize postmortem and noninvasive magnetic resonance imaging (MRI) studies to understand age-related differences and changes in brain structure. They discuss the links between brain aging patterns and cognitive decline, and present examples of activities and conditions that can influence the course of normal aging. The review also examines the mechanisms of differential brain aging, including neurotransmitter systems, stress and corticosteroids, microvascular changes, calcium homeostasis, and demyelination. Key findings include the differential vulnerability of association cortices to aging, the role of white matter hyperintensities (WMH) in cognitive decline, and the impact of hypertension and aerobic fitness on brain aging. The authors conclude by speculating on the mechanisms of differential brain aging and the potential for interventions to mitigate age-related brain changes.This review by Naftali Raz and Karen M. Rodrigue explores the patterns and biological underpinnings of cognitive and behavioral changes throughout adulthood, focusing on brain structure. The authors summarize postmortem and noninvasive magnetic resonance imaging (MRI) studies to understand age-related differences and changes in brain structure. They discuss the links between brain aging patterns and cognitive decline, and present examples of activities and conditions that can influence the course of normal aging. The review also examines the mechanisms of differential brain aging, including neurotransmitter systems, stress and corticosteroids, microvascular changes, calcium homeostasis, and demyelination. Key findings include the differential vulnerability of association cortices to aging, the role of white matter hyperintensities (WMH) in cognitive decline, and the impact of hypertension and aerobic fitness on brain aging. The authors conclude by speculating on the mechanisms of differential brain aging and the potential for interventions to mitigate age-related brain changes.