Studying Aging with RNA interference. |
Created January 5th, 2003. Copyright 2003 by Duane Hewitt
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The topic for this weekend in my review of 2002 is RNA interference (RNAi). This refinement
of antisense technology has matured in 2002 and is being applied to the study of many biological
phenomena including aging. Before I specifically discuss RNAi it is necessary to introduce some
concepts in molecular biology.
You may remember from biology that our genes are encoded in deoxyribonucleic acid (DNA) which
is found in the nucleus of our cells. Think of DNA as a reference book in the library. DNA must
remain in the nucleus for protection. Like an encyclopedia in the library it may be referred to
when necessary as a master copy that is maintained in good condition.
RNA (ribonucleic acid) serves the role of a photocopy that is made from selected pages of the
DNA reference book that provides instructions to make a protein. For the sake of analogy lets say
that someone wanted to make an ant farm and photocopied the instructions from the encyclopedia in the
library. RNA (the photocopy) can leave the nucleus (the library) and be used to carry information to
the rest of the cell.
The proteins produced from the information encoded in RNA are the action molecules of the cell,
serving functions ranging from catalysts to structural molecules. Using the photocopied instructions
to make an ant farm is analogous to the RNA instructions being used to produce proteins. The process
of information moving from DNA to RNA to protein is referred to as gene expression. There are thought
to be as many as 100,000 genes in humans but only a small subset are expressed at any one time in any
one type of cell.
Genes encoded by DNA are copied into RNA molecules by a process referred to as transcription.
The RNA molecules that encode for proteins are specifically called messenger RNA (mRNA). The mRNA are
read by ribosomes in the cell and the information is used to manufacture proteins in a process known
as translation.
RNA interference is a novel technique (first reported in 1998) that has generated a buzz in
the study of aging as well as in biology in general . It involves the use of small interfering RNA (siRNA)
or RNA interference (RNAi) to inhibit the expression of a specific gene. This technique takes advantage
of the fact that cells have a defense mechanism that degrades double stranded RNA. This has evolved
because double stranded RNA does not exist in cells unless they are infected by viruses. Therefore this
defense mechanism will break down double stranded RNA molecules.
The RNAi technique uses small RNA molecules that form pairs with the mRNA (Remember from
above "What is RNA?") molecules that normally produce proteins and cause them to be broken down before
they can produce a protein. Blocking protein production may cause a change such as an increase in lifespan.
This effect has been observed in at least one study.
The most powerful application of RNAi to the study of aging to date has been in studies of the
worm Caenorhabditis elegans which has been the subject of previous articles at this site.
The worms were fed bacteria containing siRNA for each gene of the C. elegans genome. The genes that
extended the worm lifespan were then identified and categorized.
The largest group of genes found to extend lifespan were related to the energy generating
machinery of the mitochondria. It remains open to debate how relevant these genes will be to human aging
for as obvious as it may seem it is still worth noting that humans are not worms. C. elegans have a 50%
survival rate without oxygen for 100 hours therefore their biochemistry is, in certain respects, very
different than ours. However RNAi will soon be applied to more closely related species like mice and
perhaps those results will be more similar to human aging. Further characterization of C. elegans will
also enable better identification of proteins that are relevant to the human condition.