[extropy-chat] AGING: New Theory
jpnitya at sapo.pt
Sat Apr 17 22:26:57 UTC 2004
As with all theories of ageing, my major problem is how to prove that the
mechanism you propose is a cause rather than an effect of ageing. For
instance, you place a lot of weight on double strand breaks (DSB) as a
causal factor in ageing. My advice would be for you to make a list of
proteins involved in DSB repair and the phenotype witnessed in mice or
humans when these proteins are mutated. At the IABG10 meeting in Cambridge
last September, Vijg gave a talk along these lines in considering DSB
repair mechanisms as critical in ageing but I was left mostly unconvinced.
He did not show a clear trend in mutations affecting DSB influencing
ageing. For instance, don't p53 mutations affect DSB? What about Pms2? Both
these mutations decrease the lifespan of mammals but don't appear to change
ageing. Nibrin also affects DSB in humans and yet mutations in NSB1 do not
appear to accelerate ageing--at least not to me, though Vijg has argued it
The manuscript I'm working on deals exactly with the issue of segregating
cause and effect of ageing. Animal models, such as mice, and human
progeroid syndromes offer the best evidence of causal mechanisms in ageing.
My opinion is that these are the best set of observations we have for
understanding ageing and by fitting these observations together we may be
able to develop an holistic view of the mechanisms of ageing. I'll warn you
when I have a final version of the manuscript but it looks good.
All the best,
Joao Magalhaes, Ph.D.
Website on Ageing: http://www.senescence.info
Reason's Triumph: http://www.jpreason.com
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