
Prevailing theory of aging challenged in Stanford worm study - gaika
http://www.thinkgene.com/prevailing-theory-of-aging-challenged-in-stanford-worm-study/
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sungam
In this study the authors measured the activity of most of the genes in the
worm genome and found that quite a large number change in activity
‘expression’ in old versus young worms. In general, for most genes, the amount
of protein produced from that gene is proportional to the amount of messenger
RNA transcribed. Transcription factors are proteins that regulate (either
increase or decrease) the production of messenger RNA. In this article the
authors found evidence that decreased levels of one particular transcription
factor ‘elt-3’ may account for many of the other changes in gene expression at
old age. They showed that elt-3 levels decreased with age and that this was
caused by an increase in the expression of two other transcription factors
‘elt-5’ and ‘elt-6’ which normally repress elt-3 expression. They show that if
the levels of elt-5 and elt-6 are experimentally reduced then elt-3 does not
decrease with age and the worms live longer. They propose that an increase in
elt-5 / elt-6 is a normal part of worm development but that it continues
inappropriately into adulthood where it has deleterious effects that lead to
aging. This is potentially interesting because to date there has been a huge
amount of evidence supporting the ‘unrepaired damage’ theories of aging; this
is the first evidence that aging can be a consequence of inappropriate
regulation of developmental pathways.

However this study has a number of limitations. Firstly, experimental removal
of elt-3 expression has no effect on lifespan whatever despite causing the
same changes in gene expression that are seen at old age. Secondly,
experimental reduction of elt-5 / elt-6 only increased maximum lifespan from
20 to 24 days – other mutations, such as the daf-2 mutation, increase maximal
lifespan to close to 50 days. Finally they do not address the mechanism of
increased elt-5 / elt-6 expression with age beyond speculating that it is a
disregulated developmental process; it is entirely possible that changes in
expression of these factors are simply a downstream consequence of some other
aging related change. Finally even if it were proven that aging in C elegans
is programmed like Salmon which die soon after breeding, this would likely
have no relevance to much longer living organisms such as mammals which almost
certainly age by different mechanisms.

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streety
Claimed original source:
[http://med.stanford.edu/news_releases/2008/july/aging-
worm.h...](http://med.stanford.edu/news_releases/2008/july/aging-worm.html)

Journal article:
[http://www.cell.com/content/article/fulltext?uid=PIIS0092867...](http://www.cell.com/content/article/fulltext?uid=PIIS0092867408007071)

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davi
"Natural selection can’t fix problems that arise late in the animals’ life
spans"

Another common theory is that the rate of aging in a given species is
optimized for rate of predation: if you are likely to be killed by the end of
the year, it makes sense to allocate more energy to reproduction. Whereas, if
you are likely to live to be 400, it makes sense to allocate a large portion
of your energy intake to self-maintenance.

The actual mechanism by which this optimization is implemented could easily
vary between species, but it is worth noting that caloric restriction (while
maintaining nutritional requirements) prolongs lifespan and vigor in all
species tested.

~~~
anamax
However, caloric restriction also seems to have a negative effect on
reproduction. If it also affects sexual satisfaction....

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biohacker42
Telomeres are a cancer stop mechanism.

The thing is, long lived large creatures like us have all kinds of mechanism
to repair DNA damage _and_ stop cancer that worms and mice don't.

As I once red in a Slashdot post (I think), we'd get _a lot_ more if we could
study elephants and whales, not mice and worms.

