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Heidi Tissenbaum receives NIA grant to study how aging increases susceptibility to Alzheimer’s disease

By Susan E.W. Spencer

UMass Medical School Communications

October 15, 2020
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Heidi Tissenbaum, PhD

A UMass Medical School researcher was recently awarded a $460,000, two-year grant from the National Institute on Aging to explore at the molecular level the connections between aging, health, and the onset and severity of Alzheimer’s disease.

“The idea of how you measure healthy aging is a big question,” said Heidi A. Tissenbaum, PhD, professor of molecular, cell & cancer biology.

People may be living longer, but there is a steep rise in the number of individuals with age-associated illness including Alzheimer’s disease. In the United States, more than 5 million people are affected by Alzheimer’s disease and there is no cure.

Dr. Tissenbaum previously published research conducted on long-lived mutant C. elegans that showed the genetically altered worms spent a greater portion of their life in a frail state, exhibited less activity and were more susceptible to environmental stress as they aged than typical nematodes.

The new study looks at how aging and health factors—specifically locomotion and ability to resist environmental stress—define the onset and/or severity of Alzheimer’s disease in transgenic worms that bear recombinant human amyloid A beta, one of the important proteins forming amyloid plaques found in the brains of people with Alzheimer’s disease.

The tiny worms make excellent models, according to Tissenbaum. They have just 959 cells, so one could easily ask what molecular signals make one cell different from another. And they only live around three weeks, making it feasible to perform a number of experiments and ask important questions.

“We think we have a simplified version of humans,” Tissenbaum said.

Tissenbaum’s lab uses strains of C. elegans that mimic Alzheimer’s disease by becoming immobile. Researchers can monitor how fast that happens under various conditions. These health-influencing factors include mobility and stress. Tissenbaum plans to build on this research in upcoming work looking at a high-sugar diet’s influence on healthy aging and frailty, as well.

Locomotion, or mobility, is a basic, measurable aging parameter for humans as well as C. elegans, Tissenbaum said. “You go into any nursing home and they look at the ability to go from sitting to standing and how far you can walk independently.”

Stress will be applied to the worms through their environment, either chemical or heat-induced.

In her research model, she said, “We can bring in another mutation that alters the number of days the animal is healthy or frail, manipulate that and look at what happens to the onset of paralysis or whether they stay in this paralyzed state.”

“I think about it this way,” Tissenbaum continued, “Why are elderly people more susceptible to, for example, COVID? Because they are compromised in some way. And if you’re already compromised, does this influence the onset of Alzheimer’s disease? So, we’re really trying to understand how aging makes you more susceptible to disease.”