MicroRNA Modulators of Dietary Restriction

Project Details


Dietary restriction extends lifespan, improves mid-life vigor, and retards age-related disease in
many species. Mechanisms underlying these benefits are not well understood. Defining the
cellular pathways by which dietary restriction is initiated and maintained holds potential for
combating obesity, diseases of old age such as cancer, and the general functional decline that
accompanies aging.
We have begun to investigate how microRNAs (miRNAs), small molecules that target partially
homologous transcripts to block their translational expression, impact the "quality of aging"
(healthspan) in the powerful experimental model C. elegans. In this animal, conserved genes can
be readily manipulated to address specific hypotheses regarding their activities. Moreover, nearly
all the C. elegans microRNA genes are likely to have been identified, deletions of most of these
genes have been recently generated, and our preliminary work suggests several miRNAs impact
lifespan and and/or healthspan phenotypes.
In mammalian systems, miRNA expression profiles change with different metabolic conditions,
although no studies to date have addressed changes in dietary restriction. The working hypothesis
we propose to test here is that specific microRNAs exert significant effects on the initiation
and/or maintenance of dietary restriction metabolism. If we identify these miRNAs and figure
out how they work, we could suggest manipulation of their mammalian counterparts to improve
healthy mid- and late-life.
We will therefore exploit the considerable experimental advantages of C. elegans model to identify
miRNAs that are differentially expressed in dietary restricted animals, and we will genetically test
candidates for causative action in DR induction and / or maintenance.
Because dietary restriction appears to transpire by a fundamental mechanism conserved from
nematodes to humans and because virtually nothing is known yet of microRNA modulation of
dietary restriction, our planned work should produce data relevant to human biology that pioneers
a new area in dietary restriction research with implications for therapeutic development.
Effective start/end date9/30/088/31/11


  • National Institute on Aging: $7,725.00


  • Genetics


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