Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain

Abstract

Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging.

Fig 1. Schematic of the NVU.

The NVU comprises the cerebral microvascular endothelium (shown in red), its basement membrane, and associated pericytes (yellow) and astrocytes (orange). The perivascular space exists between the endothelium and astrocytic endfeet. The endothelium provides the structural and functional basis for the blood–brain barrier (BBB), while astrocytes and pericytes control barrier induction and maintenance [7]. Junctional proteins exist between endothelial cells and astrocytes (glia limitans) to help regulate entrance into the CNS parenchyma. Image credit: Gareth R. John & Benjamin M. Laitman.

Fig 2. The impacts of exercise on age-related cognitive decline.

Three major factors have been implicated in promoting age-related cognitive decline: inflammation, neurovascular changes, and changes in CNS structure and function. Exercise has been shown to be beneficial in impacting these three categories. It has been shown to promote neurogenesis [16], increase CBF and angiogenesis [14], and reduce inflammation [4,17], correlating with improved cognitive performance. Soto et al. adds to this data (red text) by demonstrating that exercise reduces the age-related loss of pericytes, basement membrane components, and astrocyte reactivity at the NVU, and reduces the amount of complement induction in myeloid cells. Image credit: Gareth R. John & Benjamin M. Laitman.