[extropy-chat] AGING: New Theory

Joao Magalhaes 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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