Young Blood for Old Brains

Aging leads to the degradation of function and the onset of diseases in nearly all tissues and organs. Our research has been centered on brain aging, which results in cognitive decline and is a major risk factor for sporadic neurodegenerative diseases such as Alzheimer's. While brain cell- and tissue-intrinsic factors are likely essential in driving the aging process, recent studies document a remarkable sensitivity of the brain to circulatory factors. Thus, blood-borne factors from young mice or humans are sufficient to counteract aspects of brain aging and improve cognitive function in old mice. Conversely, factors from old mice are detrimental to young mice and impair cognition. We found evidence that the cerebrovasculature is an important target of circulatory factors and that brain endothelial cells show prominent age-related transcriptional changes in response to plasma. Furthermore, plasma proteins are taken up broadly into the young brain through receptor-mediated transport at the vasculature, a process that decreases with age. At the same time, proteins originating in the brain can be detected in plasma. This allows us to observe physiological shifts related to brain aging in the blood and offers novel methods to monitor individual brain physiology and aging. These findings open opportunities to identify biomarkers and regulators of aging, in general, and for the brain and other organs specifically.