2006 AFAR Research Grant: Modulation of Stress Resistance and Aging in Mice

Please give a brief summary of your AFAR research project.
An enhanced ability to withstand the effects of toxic compounds appears to be an important mediator of life span in a variety of animals. Further, this increase in stress resistance may be the result of a reduction in the level of specific hormones involved in growth. The purpose of this project is to reduce the level of these hormones in mice using dietary and pharmacological interventions to determine its effect on stress resistance and aging.

What problems are you addressing and what specific questions will your research seek to answer?
The overall goal of this project is to determine the role of specific hormones in the determination of stress resistance and life span in mice. The specific questions to be addressed are: can a brief period of undernutrition in juvenile mice slow aging, extend life span, and increase stress resistance; which tissues are more resistant to stress in mice that age more slowly than others; and, does a reduction in specific growth-promoting hormones lead to enhanced stress resistance, slowed aging and extended life span?

What aspects of your project are most interesting from a scientific point of view?
The notion that events occurring during the first weeks to months of life could have long-term effects on metabolism and disease incidence is not new to science; however, whether or not these events can alter the rate of aging is largely unexplored. This project will directly address this issue. In addition, although there is substantial correlative evidence linking a reduction in growth-promoting hormones to the induction of stress resistance, there is still little direct evidence. This project will provide a direct test of this hypothesis using a specific drug known to reduce the activity of these hormones.

What are the implications of your research for age-related diseases and disorders?
If it can be shown that an enhanced ability to resist stress is important for successful aging, then determining which hormones are involved will give us the ability to improve our resistance to stress using specific drugs or dietary interventions in order to keep the elderly population healthier for longer.

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