Prevailing theory of aging challenged in Stanford worm study

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.

Claimed original source: http://med.stanford.edu/news_releases/2008/july/aging-worm.h...

Journal article: http://www.cell.com/content/article/fulltext?uid=PIIS0092867...

"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.

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.