Age-Related Alterations in Brain Perfusion, Venous Oxygenation, and Oxygen Metabolic Rate of Mice: A 17-Month Longitudinal MRI Study

Background: Characterization of physiological parameters of the aging brain, such as perfusion and brain metabolism, is important for understanding brain function and diseases. Aging studies on human brain have mostly been based on the cross-sectional design, while the few longitudinal studies used relatively short follow-up time compared to the lifespan. Objectives: To determine the longitudinal time courses of cerebral physiological parameters across the adult lifespan in mice. Methods: The present work examined longitudinal changes in cerebral blood flow (CBF), cerebral venous oxygenation (Y(v)), and cerebral metabolic rate of oxygen (CMRO(2)) using MRI in healthy C57BL/6 mice from 3 to 20 months of age. Each mouse received 16 imaging sessions at an ~1-month interval. Results: Significant increases with age were observed in CBF (p = 0.017) and CMRO(2) (p < 0.001). Meanwhile, Y(v) revealed a significant decrease (p = 0.002) with a non-linear pattern (p = 0.013). The rate of change was 0.87, 2.26, and −0.24% per month for CBF, CMRO2, and Y(v), respectively. On the other hand, systemic parameters such as heart rate did not show a significant age dependence (p = 0.47). No white-matter-hyperintensities (WMH) were observed on the T(2)-weighted image at any age of the mice. Conclusion: With age, the mouse brain revealed an increase in oxygen consumption. This observation is consistent with previous findings in humans using a cross-sectional design and suggests a degradation of the brain's energy production or utilization machinery. Cerebral perfusion remains relatively intact in aged mice, at least until 20 months of age, consistent with the absence of WMH in mice.