Cerebral microhemorrhages and gait abnormalities in aging
Description: Project Narrative The increasing prevalence of multifocal cerebral microhemorrhages (also known as “cerebral microbleeds) is a significant problem in the aging population, which progressively impair neuronal function and contribute to cognitive decline and gait disorders.Our hypothesis is that aging-induced accumulation of senescent endothelial cells in the cerebral microcirculation is responsible for a pro- fragility microvascular phenotype: senescent cells release activated matrix proteinases and other paracrine factors ("senescence-associated secretory phenotype" or SASP), which promote structural maladaptation to high pressure, degradation of collagen and remodeling of extracellular matrix, thus creating loci of least resistance that can easily burst upon induction of hypertension. Using an approach that combines neuroanatomical analysis, innovative imaging techniques, and integrative cerebrovascular physiology, we will be able to test novel, translationally relevant interventional strategies, senolytics, for prevention of CMHs and protecting cerebral function in the elderly as well.
Funder: National Institute on Aging
Funding type: research
Funder scheme: R01
Start date: 2017-09-15
End date: 2030-06-30
Investigator: ANNA CSISZAR
Institution: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
Funded outputs count: 147
Funder award ID: R01AG055395
OpenAlex ID: G9000892147