[extropy-chat] AGING: real progress

Joao Magalhaes jpnitya at sapo.pt
Mon Feb 23 07:30:33 UTC 2004


Although the p66 mice live longer, there is little information regarding 
specific age-related pathologies. I don't remember reading anything 
regarding cancer rates in p66 -/- mice, so I would assume cancer rates do 
not change but I could be wrong.

As for WS and p66, I think you missed my point. At a molecular level they 
may have different roles. Yet I was looking at aging from a cell population 
perspective. At a tissue level, p66 decreases apoptosis, meaning tissues 
can have cells dividing slower or have less cells dividing to maintain 
tissue homeostasis. In WS, cells divide slower and less vigorously, meaning 
there must be more cells dividing to maintain homeostasis. The bottom line 
is: in p66 you have a higher production of cells while in WS you have a 
lower production of cells, meaning p66 allows cells to divide less 
frequently while WS obliges cells to divide more frequently. From this 
perspective it makes sense that p66 delays aging while WS decreases 
longevity and accelerates aging.

Just like you can't understand a painting by looking too closely, maybe you 
have to zoom out from the molecular perspective to understand aging.

Apoptosis is also affected by WS, though I'm not sure whether it's 
increased or decreased.

A couple of references on p66:

Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, 
P. P., Lanfrancone, L., and Pelicci, P. G. (1999). "The p66shc adaptor 
protein controls oxidative stress response and life span in mammals." 
Nature 402(6759):309-313.

Nemoto, S., and Finkel, T. (2002). "Redox regulation of forkhead proteins 
through a p66shc-dependent signaling pathway." Science 295(5564):2450-2452.

And a couple of references on the link between WS and apoptosis:



All the best,


PS: A good question then would be why mice mutant for WRN do not age faster 
since their cells divide slower in culture.

Joao Magalhaes (joao.magalhaes at fundp.ac.be)

Website on Aging: http://www.senescence.info
Reason's Triumph: http://www.jpreason.com  

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