Tuesday, July 09, 2024

Improving 'health span' through slowing age-related cognitive decline



Researchers earn $2.3 million in grants from Hevolution Foundation



UNIVERSITY OF OKLAHOMA

Shannon Conley, Ph.D. 

IMAGE: 

RESEARCHER SHANNNON CONLEY, PH.D., STUDIES AGE-RELATED COGNITIVE IMPAIRMENT AT THE UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE.

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CREDIT: UNIVERSITY OF OKLAHOMA




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.

“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.

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.”

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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.


 

UQ research reveals exercise brain boost can last for years



High-intensity interval exercise improves brain function in older adults for up to 5 years



UNIVERSITY OF QUEENSLAND

Exercise and cognition 

VIDEO: 

EMERITUS PROFESSOR PERRY BARTLETT DISCUSSES WHAT THE STUDY TELLS US ABOUT EXERCISE AND BRAIN FUNCTION

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CREDIT: THE UNIVERSITY OF QUEENSLAND



A longitudinal study by University of Queensland researchers has found high-intensity interval exercise improves brain function in older adults for up to 5 years.

Emeritus Professor Perry Bartlett and Dr Daniel Blackmore from UQ’s Queensland Brain Institute led the study in which volunteers did physical exercise and had brain scans. 

Emeritus Professor Perry Bartlett and Dr Daniel Blackmore have shown high intensity exercise boosts cognition in healthy older adults and the improvement was retained for up to 5 years. 

Emeritus Professor Bartlett said it is the first controlled study of its kind to show exercise can boost cognition in healthy older adults not just delay cognitive decline.

“Six months of high-intensity interval training is enough to flick the switch,” Emeritus Professor Bartlett said.

“In earlier pre-clinical work , we discovered exercise can activate stem cells and increase the production of neurons in the hippocampus, improving cognition.

“In this study, a large cohort of healthy 65 – 85-year-old volunteers joined a six-month exercise program, did biomarker and cognition testing and had high-resolution brain scans.

“We followed up with them 5 years after the program and incredibly they still had improved cognition, even if they hadn’t kept up with the exercises.”

Ageing is one of the biggest risks for dementia, a condition that affects almost half a million Australians.

“If we can change the trajectory of ageing and keep people cognitively healthier for longer with a simple intervention like exercise, we can potentially save our community from the enormous personal, economic and social costs associated with dementia,” Emeritus Professor Bartlett said. 

Emeritus Professor Bartlett and Dr Blackmore worked in collaboration with Honorary Professor Stephan Riek and The School of Human Movement and Nutrition Sciences at UQ.

During the study, the researchers assessed the impact of three exercise intensities: 
•    Low – predominantly motor function, balance and stretching
•    Medium – brisk walking on a treadmill
•    High – four cycles running on a treadmill at near maximum exertion

Dr Blackmore said only the high-intensity interval exercise led to cognitive improvement that was retained for up to 5 years.

"On high-resolution MRI scans of that group, we saw structural and connectivity changes in the hippocampus, the area responsible for learning and memory,” Dr Blackmore said.

“We also found blood biomarkers that changed in correlation to improvements in cognition.

“Biomarkers can be useful in predicting the effectiveness of the exercise a person is doing.”

With 1 in 3 people aged 85 years likely to develop dementia, Dr Blackmore said the impact of the research was far-reaching.  

“Our finding can inform exercise guidelines for older people and further research could assess different types of exercise that could be incorporated into aged care,” he said.

"We are now looking at the genetic factors that may regulate a person’s response to exercise to see if we can establish who will and who will not respond to this intervention.

“The use of biomarkers as a diagnostic tool for exercise also needs further research.”

The research was published in Aging and Disease.

It receives ongoing support from the Stafford Fox Medical Research Foundation.

 Exercise and cognition [VIDEO] |

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