Young blood rejuvenating cerebral microcirculation in old mice
Description: Aging-induced cerebromicrovascular endothelial dysfunction is the primary factor in impairment of neurovascular coupling (NVC) responses and dysregulation of cerebral blood flow (CBF), contributing to the genesis of vascular cognitive impairment and dementia (VCID). Heterochronic blood exchange (HBE) in mice as well as bioassay experiments in cultured endothelial cells treated with sera from human patients, non-human primates and rodent models of aging provide compelling evidence that implicates non-cell autonomous mechanisms as key drivers of endothelial aging processes. Guided by analysis of vascular transcriptomic changes in heterochronic parabiont mice the objective of the proposal is to elucidate the mechanism of cerebromicrovascular rejuvenation activated by specific circulating anti-geronic factors present in young blood. The central hypothesis is that young blood rescues the age-related decline in signaling via the NAD+/SIRT1 axis which can result in vascular rejuvenation, attenuation of endothelial oxidative stress, improved endothelial vasodilator function and restoration of endothelial angiogenic processes. The resulting increases in CBF and NVC responses reduce ischemic loci, promoting brain health. It is predicted that disruption of the NAD+ /SIRT1 axis will prevent cerebrovascular rejuvenation by HBE in aged mice. The proposed studies will elucidate the involvement of two key mechanisms in the protective effects of HBE against cerebromicrovascular aging and the pathogenesis of VCID.
Funder: American Heart Association
Amount: $64,070
Funding type: training
Funder scheme: Predoctoral Fellowship
Start date: 2022-01-01
End date: 2023-12-31
Investigators: Rafal Gulej, Rafal Gulej
Institution: Board of Regents of the University of Oklahoma, Health Sciences Center
Funded outputs count: 2
Funder award ID: 916225
OpenAlex ID: G7605328273