Skip Navigation

Researchers Earn $2M in Grants for Studies on Age-Related Cognitive Decline

NEWS

Researchers Earn $2M in Grants for Studies on Age-Related Cognitive Decline


By

Date

July 9, 2024

Media Contact

April Wilkerson
april-j-wilkerson@ouhsc.edu


OKLAHOMA CITY, OKLA. – Two University of Oklahoma researchers have been awarded more than $2 million in grants from the Hevolution Foundation to further their studies on age-related cognitive impairment, with an emphasis on improving “health span,” or the number of years a person remains healthy.

While modern medicine can help extend a person’s life span, researchers are increasingly studying ways to increase their healthy years of life. Because the process of aging increases the risk for memory problems and dementia, researchers must understand why as a first step toward delaying cognitive issues until later in life. The Hevolution Foundation invests in science that aims to uncover the root causes of aging.

“As we have longer life spans, it’s really important to identify ways to simultaneously promote increased health spans. It’s challenging when you have loved ones who have severe illness or cognitive impairment, yet they are not dying; they are physically able to keep living. We want to help people stay healthier longer,” said Hevolution grant recipient Shannon Conley, Ph.D., an assistant professor of cell biology in the OU College of Medicine. She is leading the work of the grant with Anna Csiszar, Ph.D., a professor of neurosurgery in the OU College of Medicine.

Blood Vessel Function

In their project, they seek to better understand how two types of cells in blood vessels work together for brain health but become dysfunctional as a person ages. Endothelial cells, which line the blood vessels, and smooth muscle cells, which are on the outside of the vessels, collaborate to help the brain respond to everyday stimuli, like sound or taste. During aging, they can undergo a process called cellular senescence, a kind of limbo when the cells aren’t dead but neither are they functioning normally and proliferating.

As a result, the cells can no longer perform their usual tasks, which then causes the blood vessels to have trouble contracting and relaxing normally. That vascular dysfunction sets the stage for cognitive impairment and eventually dementia. The researchers want to understand how cellular senescence leads to blood vessel dysfunction.

“We believe the link is something called de-differentiation: The endothelial cells and smooth muscle cells essentially lose their identity during senescence and become generic cells that don’t function well,” Conley said. “Understanding these mechanisms that lead to age-related defects in blood vessel function is really important for making progress toward a treatment or cure for dementia. You wouldn’t necessarily think that the blood vessels are the place to look, but there is so much evidence that blood vessel dysfunction is one of the earliest changes in the brains of people who develop dementia.

Shannon Conley.
Shannon Conley, Ph.D.

“When we think about dementia, we think about damage to the neurons in your brain,” she added. “But if the blood vessels in the brain are not functioning well, then the neurons don’t have enough energy or oxygen and eventually will degenerate. In addition, the blood vessels are very important for clearing waste materials, so if the blood vessels aren’t working properly, then you have an accumulation of abnormal material that will contribute to neuronal dysfunction.”

Metabolic Factors and Aging

The second grant recipient, Sreemathi Logan, Ph.D., an assistant professor of biochemistry and physiology in the OU College of Medicine, seeks to understand the metabolic factors, including obesity, that influence cognition during aging. A central question of her research is why some people’s brains seem to be resilient, while others are susceptible to cognitive problems and diseases like Alzheimer’s. For her studies, she separates aging mice into two groups – those with “intact” cognition and those with impaired cognition.

“Because we separate mice into different subgroups of varying cognitive function, we can better try to understand what specific cells are doing in the brain that contribute to healthy brain aging vs. impaired cognition,” she said. “My previous research has shown that mice mirror the differential cognitive abilities that humans exhibit and thus are a good model to investigate the incidence and progression of dementia with age.”

The group of cognitively impaired, older mice experience dysfunction of their mitochondria, which are responsible for providing energy to the brain. Loss of mitochondrial function can lead to persistent inflammation that is driven by cellular senescence, a hallmark of aging. Even though senescent cells have stopped dividing, they remain active, spewing out harmful substances that cause inflammation, further impairing cognition.

Sreemathi Logan.
Sreemathi Logan, Ph.D.

With this grant, Logan is studying the brain-adipose axis: how excess fat in the body, especially around the belly, affects cognition during aging. In particular, she is testing whether a ketogenic diet – high fat and reduced carbohydrates – can target cellular senescence. Existing research suggests that reducing carbohydrates, even in a high-fat diet, helps the body use fat more efficiently. Theoretically, that would lower the inflammatory factors of senescence and reduce the negative effects of fat on the brain.

Logan’s grant also allows her to investigate whether senolytics – drugs that target senescent cells – can positively affect cognition by regulating fat metabolism, the process of breaking down fat in the diet so it can be used for energy.

“Cognitive health is an important part of health span,” Logan said. “By understanding the biological underpinnings of why some mice perform better than others, we hope to eventually translate our findings to humans with varying cognitive abilities and design individualized treatments to improve cognitive function in older adults.”

Felipe Sierra, Ph.D., chief science officer for Hevolution, said the foundation is proud to support the advancement of research in the biology of aging.

“The research pursued by Drs. Conley and Logan is at the cutting edge in the field of age-related cognitive decline,” Sierra said. “The competive process for these awards highlights the achievements of these grantees and the University of Oklahoma. We are particularly gratified to support new investigators at the difficult stage of establishing their credentials in the field, and we look forward to the achievements of these two outstanding researchers.”

About the project

Shannon Conley, Ph.D., received the Hevolution Foundation – Geroscience Research Opportunities award, for a total of $2 million over five years. Sreemathi Logan, Ph.D., was awarded the Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience, for a total of $375,000 over three years.

About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university located in Norman, Oklahoma. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. OU was named the state’s highest-ranking university in U.S. News & World Report’s most recent Best Colleges list. For more information about the university, visit ou.edu.


Recent News

Campus & Community
July 12, 2024

OU Hudson College of Public Health Earns Reaccreditation

The Hudson College of Public Health on the University of Oklahoma’s Health Sciences campus has earned reaccreditation from the Council on Education for Public Health.


Impact
July 11, 2024

$5 Million Grant to OU Continues Work of Oklahoma Dementia Care Network

The University of Oklahoma is expanding the efforts of the Oklahoma Dementia Care Network. The program aims to improve health outcomes for people living with dementia and their caregivers through statewide geriatric workforce development.


Research
July 10, 2024

Engineering Professor Receives Prestigious Junior Faculty Award for Nitrate Conversion Research

Kasun Gunasooriya, Ph.D., an assistant professor in the University of Oklahoma School of Sustainable Chemical, Biological and Materials Engineering, has received a Ralph E. Powe Junior Faculty Enhancement award from the Oak Ridge Associated Universities. He was selected for his research on converting nitrate captured during the water purification process into ammonia, reducing water pollutants while generating an important fertilizer for global agriculture.