New Scholar Award in Aging
David A. Sinclair, Ph.D.
Harvard Medical School

Identification of Genes and Compounds that Extend Yeast Life Span

Belying the complexity of the aging process, relatively minor changes to the environment or genetic make-up of an organism can dramatically slow the rate at which it ages. The question thus arises: How can seemingly simple changes have such profound effects on aging? Recent findings suggest that the pace of aging is actually governed by a surprisingly simple regulatory system that may have evolved to allow organisms to survive in stressful environments by redirecting resources from reproduction to stress resistance. The goal of our research is to use simple model organisms such as baker's yeast and a nematode worm (Caenhorabditis elegans) to identify and characterize genes that act in the conserved aging regulatory pathway.

It has been known for over 30 years that aging in rats can be slowed simply by restricting their calorie intake, in a dietary regime known as "calorie restriction". Interestingly, calorie restriction has been shown to affect aging in every organism tested thus far including yeast, fish, spiders and possibly primates. Using budding yeast as our primary model system we have identified numerous genes that are involved in extending life span under conditions of calorie restriction. By changing the copy number of these genes we have been able to significantly extend life span in yeast. All of the genes we have identified thus far have counterparts in C. elegans and humans. Many of these affect particular biosynthetic pathways and/or the packing of DNA into chromatin. Our ultimate goal is to identify small molecules that alter the statement of longevity genes or the activity of their gene products. In this way we hope to be able to devise drugs that slow onset of age-associated diseases by mimicking a state of calorie restriction, even when ample calories are consumed.

Contact Dr. Sinclair.