[extropy-chat] AGING: research progress

[Robert J. Bradbury]

Well, it looks like the mitochondrial theory of aging
is getting some support.  Scientists created mice
with a defective mitochondrial DNA polymerase and it
significantly shortened their lifespans.

URL:
http://www.sciencedaily.com/releases/2004/05/040527234844.htm

Abstract from PubMed:
Point mutations and deletions of mitochondrial DNA (mtDNA)
accumulate in a variety of tissues during ageing in humans, monkeys and
rodents. These mutations are unevenly distributed and can accumulate
clonally in certain cells, causing a mosaic pattern of respiratory chain
deficiency in tissues such as heart, skeletal muscle and brain. In terms
of the ageing process, their possible causative effects have been
intensely debated because of their low abundance and purely correlative
connection with ageing. We have now addressed this question experimentally
by creating homozygous knock-in mice that express a
proof-reading-deficient version of PolgA, the nucleus-encoded catalytic
subunit of mtDNA polymerase. Here we show that the knock-in mice develop
an mtDNA mutator phenotype with a threefold to fivefold increase in the
levels of point mutations, as well as increased amounts of deleted mtDNA.
This increase in somatic mtDNA mutations is associated with reduced
lifespan and premature onset of ageing-related phenotypes such as weight
loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature
of the spine), osteoporosis, anaemia, reduced fertility and heart
enlargement. Our results thus provide a causative link between mtDNA
mutations and ageing phenotypes in mammals.

URL for Nature article:
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v429/n6990/abs/nature02517_fs.html

Now it looks like the problem is due to an accumulation of mutations in
the mitochondrial DNA.  But whether that problem causes decreased
production of ATP (meaning the cells may have reduced protein production
capacity) or in more production of free radicals and is thus linked to the
free radical theory of aging (which IMO is linked in complex ways to the
somatic mutation theory of aging) doesn't seem to be clear.

However it should be considered that there are probably
many ways to shorten lifespan -- but that doesn't immediately
translate to methods that may be used to extend lifespan.

Robert