TitleMicroRNAs modulators of dietary restriction and aging in Caenorhabditis elegans
NameShah, Mitalie B. (author), Padgett, Richard W (chair), Driscoll, Monica (internal member), Rongo, Christopher (internal member), Rutgers University, Graduate School - New Brunswick,
SubjectCell and Developmental Biology,
DescriptionAging is a universal phenomenon that is experienced by diverse organism. Aging can be
defined broadly as progressive decline in cellular functions in an organism with
increasing age, decreasing the ability to survive challenges. Understanding and
deciphering the mechanisms involved in this process has been a key focus of current
science. An important goal of aging research is not only to identify different approaches
to maximize human lifespan, but to also improve the quality of life with increasing age.
MicroRNAs (miRNAs) are known to regulate a range of biological processes including
cell differentiation, cell death, development, oncogenesis, and metabolism, but little is
known about how they impact the biology of aging. Our research mainly focuses on
identifying how miRNAs, small molecules that target partially homologous transcripts to
block their translational expression, influence healthspan and lifespan in C. elegans. We
have identified many mir deletion mutants that impact different aspects of aging like
longevity, metabolic and muscle aging. There are four measures that reflect how well or
how poorly the animals are aging: age pigment levels, swimming body bend frequency
assays, pharyngeal pumping rates, and lifespan studies. Applying these tests, we have studied miRNAs mir-1, mir-256 and mir-238 in a focused manner. Importantly, we have also found that the mir-80(Δ) mutant modulates dietary restriction- a metabolic condition
in which reduced caloric intake significantly increases lifespan in a wide range of species.
mir-80(Δ) mutant exhibits multiple parameters of healthy aging, reduced reproductive
phase and expression of molecular reporters associated with dietary restriction. Using
RNAi knockdown, we have identified multiple transcription factors (SKN-1, DAF-16 and
HSF-1) and a transcriptional co-factor CBP-1 that seems to play an important role in
making mir-80(Δ) long-lived through dietary restriction. In short, we have discovered the
first ever microRNA (miR-80) that modulates dietary restriction and longevity in C.
elegans. In sum, we have shown that microRNAs can modulate various aspects of C.
elegans healthspan, and determined the role of some microRNAs in aging, muscle
physiology and dietary restriction. Becaue miRNA signaling can be conserved, our
studies will provide clues to similar processes in vertebrates, including humans.
NoteIncludes bibliographical references
Noteby Mitalie B Shah
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.