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