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Understanding the Stress of Aging and Diabetes

Amy Wagers, Ph.D., of Joslin Diabetes Center

Amy Wagers, Ph.D.

Thursday, May 19, 2011

Type 2 diabetes is a disease that increases in incidence with age and is associated with significant stress, and many Joslin research projects seek to understand the connection between these risk factors and development of diabetes. Two principal investigators lead basic research projects—one on adult stem cells and one on worms—that explore these related mechanisms, helping to move toward therapies that may slow the progression of the disease or minimize its effects.

Amy Wagers, Ph.D., studies tissue repair and regeneration in aging, focusing primarily on the role of two types of stem cells, one that makes blood and another that makes skeletal muscle. Her lab has documented the ways in which these stem cells lose functionality over time, and also has demonstrated that components in the blood of young mice may help to revive stem cells in old mice.

“We’re noticing an increasing number of similarities in tissue function between aging individuals and individuals with diabetes,” says Dr. Wagers. “Many of the cells and systems that are altered in old mice are also altered in mice we’ve made diabetic.”

Wagers’ work will aid in understanding how diabetes advances, how its effects may be accelerated by age-related factors, how tissues damaged by diabetes might be repaired, and how the deficits in cell production that accompany aging might be slowed.

T. Keith Blackwell, M.D., Ph.D., studies how cells and organisms protect themselves against stress, and the relationship to aging and chronic diseases such as diabetes. His lab works with the C. elegans worm, which is all of a millimeter long.

“The worm is a great animal for this work because we can do sophisticated genetic manipulations on a large scale to identify molecular processes that are involved in handling stress,” says Dr. Blackwell. “It helps us in discovering ‘wiring diagrams’ for fundamental mechanisms that then can be looked at in higher organisms such as mice and humans.”

Some projects in the Blackwell lab study stress in the endoplasmic reticulum—a structure in the cell that folds up proteins before they can do their work, and gets a real workout in beta cells.

“It’s hard for beta cells to pump out lots of insulin, particularly under conditions such as type 2 diabetes,” he says. “We look at mechanisms that defend the cell against this type of stress.”

Additionally, his lab examines the defensive mechanisms that guard against oxidative stress, in which a toxic form of oxygen builds up in tissues. This is another major contributor to the damage inflicted on beta cells and other cells impaired in diabetes, Dr. Blackwell explains.

Keith Blackwell, M.D., Ph.D.

Amy Wagers, Ph.D.

Page last updated: December 21, 2014