what's ageing, cont

Matt Gray gray at boulder.Colorado.EDU
Sun Aug 18 12:03:40 EST 1991

In article <178539 at tiger.oxy.edu> hoopes at oxy.edu (Laura L. M. Hoopes) writes:
>I have been reading with interest the various ideas people have on the
>control of ageing rate...  It seems to me...  that the
>ageing process is mor really controlled by the organism but is an effect of
>the tendency of things to fall apart (thermodynamics).

Is there really any evidence that aging, per se, is caused by "things falling

>The differences
>between organism, cells, etc in this theory come from the different
>abilities of these organisms, cells, etc to maintain their life processes
>by repair, prevention, etc, but they still result in different ageing

Certainly, different organisms vary in their abilities to combat "environmental
abuses."  However, cells in culture should be normalized (in a sense) with 
respect to their environment.  Aside from cosmic irradiation (I loathe this 
concept), what else could cause things inside cells to fall apart in a tissue
culture flask?  Yet in culture, cells (especially fibroblasts) derived from 
different organsisms do display different rates of aging.  

Are these rates determined genetically or are they merely a result of an 
accumulation of damage?  Sorry, I know this is getting to be the age-old 
question in cell aging but I wanted to throw it out there to see what people 
currently think about it.

>The real puzzle...  is the germ line...how are these cells protected
>from the ageing process or reset to the non-aged conditions?  Laura

One of the unique features of germ line cells is that, prior to conception,
they do not undergo a tremendous amount of proliferation.  They must, of coarse,
be derived from preexisting cells that have undergone some amount of 
proliferation during development.  However, the majority of cell types that do
age, not counting cells that terminally differentiate like nerve and muscle 
etc..., undergo constant or intermittent proliferation in the organism during
its life.   

So, how indeed is the developmental program reset in the germ line?  You are 
certainly aware of the concept of "biological clocks."  Although no such 
mechanism has been identified in mammalian cells (or in any cells, to my 
knowledge), DNA methylation is a strong candidate for a means of resetting the 
aging clock.  In fact, DNA methylation patterns do appear to be reestablished 
during gametogenesis and early development.  Although the function(s) of DNA 
methylation in mammalian cells is uncertain at present, a "clock" mechanism may 
not have to be solely related to gene expression, per se.  That is, resetting
the clock could be a structural phenomenon that not only affects genes, but
rather all of the DNA in a cell.  These structural features that do not include
genes could be involved in proliferative capacity in some way, i.e., aging.

Does anyone know of any other possible mechanisms for bilogical clocks?

Matt \      /\/\  /|email: gray at boulder.Colorado.EDU
  /***\  /\/*/**\/*|Department of Molecular, Cellular, and Developmental Biology
 /  /\ \/**\/    \ |University of Colorado at Boulder, Boulder, CO  80309-0347  
/__/**\/____\_____\|(303) 492-7848

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