Age-related vascular cognitive impairment and dementia (VCID), a subgroup of Alzheimer’s Disease and Related Dementias (ADRD) is a common cause of disability and reduced quality of life among the elderly.  Extensive recent data have demonstrated that microvascular pathologies in the brain play a central role in these processes.

We are interested in how aging affects the microvasculature of the brain and retina. In particular we’re interested in understanding the underlying cellular and molecular mechanisms that lead to vascular dementia as well as age related vascular diseases of the retina and choroid.

Through a deep exploration of the foundational biology of aging, our studies provide critical insights into how common aging mechanisms play a role in healthspan-limiting pathologies. Ultimately, our investigations lay the groundwork for the development of novel therapeutic strategies preserving cognitive function and enhancing the overall quality of life for our aging population.

For more information, reach out to Dr. Conley at shannon-conley@ouhsc.edu

What role does IGF-1 play in vascular smooth muscle cells in brain aging?

Cerebral microhemorrhages (CMH) are the result of rupture of small intracerebral blood vessels and progressively impairs neuronal function. The incidence of CMH dramatically increases with age, yet the underlying cellular mechanisms for CMH and increased vascular fragility are unknown. Blood vessel integrity requires plasticity of vascular smooth muscle cells (VSMCs), but aging fundamentally alters VSMC plasticity. Circulating levels of the vasoprotective peptide insulin-like groth factor 1 (IGF-1) are dramatically decreased with age. Our hypothesis is that impaired VSMC plasticity and function due to IGF-1 deficiency has a fundamental role in increased cerebrovascular fragility and development of CMH and cognitive decline with age.

How does aging lead to maladaptive changes in brain vascular cells?

The precise mechanisms by which aging influences endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) leading to age related cerebrovascular fragility remain elusive. Our hypothesis is that senescent brain cells trigger endothelial-to-mesenchymal transition in ECs and induce maladaptive phenotypic switching in VSMCs. These transdifferentiation processes are characterized by the down-regulation of cell-specific genes and the acquisition of inflammatory attributes, collectively compromising vascular function and structure, creating susceptible sites for vascular rupture ultimately culminating in cognitive decline.

How does aging change the choroidal vasculature?

The choroidal vasculature is much less studied than the retinal vasculature. Yet this unique tissue is responsible for supplying oxygen and nutrients to most of the outer retina, where photoreceptors are responsible for intiating vision. Choroidal pathologies contribute to age-related macular degeneration. Our lab is interested in understanding the cellular and molecular changes in the choroidal capillaries that occur with age, increasing risk for disease.

The Conley lab currently has an outstanding blend of PhD students, research assistants, and undergraduate researchers. We are part of the broader VCID (Vascular Cognitive Impairment and Dementia) team at OUHSC and collaborate closely with the other five labs that comprise that team.

Click here to learn more about current team members.

We’re always looking for dedicated Graduate Students (taken through the Graduate Program in Biomedical Sciences at OUHSC) and Postdocs. If you’re interested in joining the Conley lab, email Dr. Conley at shannon-conley@ouhsc.edu