[KuevDulin]

FIGHT AGING! NEWSLETTER
March 26th 2012

"Mitochondria crowd your cells, roving descendants of ancient bacteria
that were long ago co-opted to serve as power plants, turning food
into adenosine triphosphate (ATP), the energy store chemical used to
power cellular machinery. As a legacy of their bacterial origins,
mitochondria carry their own DNA, separate from that in the cell
nucleus. Making ATP is a messy business, creating all sorts of
reactive molecules as byproducts, and that mitochondrial DNA is more
vulnerable than the safely enclosed nuclear DNA. The balance of
evidence strongly implicates mitochondrial DNA damage as one of the
contributing causes of aging. A damaged gene can no longer be used as
a blueprint for the process of gene expression that produces the
protein machinery that is vital to the operation of a mitochondrion,
and from there matters only go downhill - it's a long road that ends
up at atherosclerosis, neurodegeneration, and many other forms of
advanced age-related degeneration.

"Thus finding ways to repair mitochondrial DNA (mtDNA) is of great
importance - but this is still a minority field of science in
comparison to stem cell medicine or cancer research. Nonetheless,
mitochondrial repair has been attracting some attention in the past
week, as an important new line of research made it to the press
release and publicity stage. The technique demonstrated is not really
repair, per se, more a method of working around damage to
mitochondrial genes - but it looks to be a great improvement over
existing methodologies in terms of cost, time, and difficulty. This
may enable broader and faster progress towards therapies that can
remove the harm caused by damaged mitochondria.

"The new method is a way to deliver more or less arbitrary RNA to
mitochondria, which should allow for continued function even after
mutational damage to important genes. Production of RNA is a first
step in the convoluted process of gene expression - by which genes are
used as a blueprint for proteins - so it's quite possible to skip the
gene and start with the RNA. This shortcut is the basis for a range of
modern life science research, and one obvious use is to correct for a
missing or damaged gene: find a way to provide the patient with an
ongoing supply of suitably crafted RNA molecules targeted to the right
places in his or her cells and it won't matter that the gene is
broken.

"I should note that there are only thirteen genes in the mitochondria
that are important for the purposes of this discussion, but the
process of producing repairs or workarounds for each one has been
hard, very different for each of them, slow, and difficult up until
this point. A method that works in a very similar way for all of them
is a big deal."