New NIH-funded studies will examine risk factors for age-related diseases

Liou Sun, Ph.D.

biology lab at the University of Alabama at Birmingham gains increased funding with the addition of two grants from the National Institutes of Health. The research team will use the funding to better understand the correlation between the biology of aging and neurodegenerative diseases such as Alzheimer’s disease.

The mechanisms responsible for the age dependence of the onset of neurodegeneration are unknown, which represents a fundamental problem in both neuroscience and biogerontology — the study of biological processes of aging.

Liou Sun, Ph.D., an assistant professor in UAB’s College of Arts and Sciences who studies the biology of aging, says previous studies provide strong evidence that metabolic derangements including obesity, metabolic syndrome and Type 2 diabetes constitute major risk factors for age-related diseases, including dementia and Alzheimer’s; but the mechanisms involved remain to be understood.

“We need to learn more about why these metabolic derangements are so powerfully linked to neurodegenerative diseases,” Sun said. “We chose to look at previous studies surrounding the interaction of aging with Alzheimer’s in particular, to learn more about these types of diseases.”

Alzheimer’s is a progressive neurodegenerative condition characterized by dementia, deposition of beta amyloid plaques and neurofibrillary tau tangles. Despite progress in developing treatments for the symptomatic relief of Alzheimer’s, most drugs exhibit only marginal benefits, and no cure currently exists.

With those limitations in mind, Sun’s team will look at previous models that have shown success in animals to develop a new model looking at the interaction of aging with Alzheimer’s, so that scientists can better analyze why the aging brain behaves in certain ways, and gain more information about how drugs can target the disease.

The growth hormone signaling functions as a central regulator of metabolism and energy use, and it coordinates the physiological responses of the entire organism through hormonal signaling. Mutant animals with reduced growth hormone signaling not only are long-lived, but are protected against age-associated decline in memory and learning.

Thus, combining delaying aging models with Alzheimer’s disease models exhibiting various phenotypic effects provides a novel opportunity to develop new models that will allow studies focused on the interaction among aging, metabolism and neurodegeneration.Methionine restriction has been shown previously to extend lifespan and delay aging in both rats and mice, dramatically decrease body weight and adiposity, and improve insulin sensitivity and ameliorate aging-associated alterations in glucose and lipid homeostasis.

“Our NIH-funded studies will determine whether suppression of the growth hormone signaling and methionine restriction will prevent development of behavioral and histopathologic abnormalities of Alzheimer’s disease, and whether that phenotype can serve as a model to study the interaction of aging with Alzheimer’s,” Sun said. “This will provide a new perspective to understand human brain disorders.”

The two new NIH grants total $762,905 and will support Sun’s team in their research for the next several years.

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