Telomeric Theory - Related Research - Genes & Aging

Excelife excelife at
Sun Oct 4 00:42:30 EST 1998

In article <36167359.5E94D4C5 at>, james at says...
>> The second most dramatic changes in genetic expression occurs at the time 
>> the cell enters senescence.  These have been discussed before and I won't 
>> bother with the details here.
>This statement is fairly unsupported.  Not nearly enough
>work has been done to say whether this is true or not.  Just
>because it seems intuitive that between terminal
>differentiation and visible senescence nothing much would
>change (since we don't see phenotypic changes in culture),
>doesn't mean that is what is happening.  In fact, there are
>some theories that would argue that aging is a continuous
>change starting at the onset of maturity, and that the
>visible manifestation of senescence is only seem once things
>get REALLY out of control and cause the cell to function

I see your point, that just because we know of genetic changes occurring 
during initial development and after senescence, there may be just as much or 
even more change during the interim that we are just not aware of.

This could be the case and I would be interested in seeing research that 
shows what, if any, changes in gene expression does occur during this period.

One piece of evidence in support of this gradual change is that the telomeres 
are shortened during this period.  There are approx. 10 population doublings 
that occur between maturity and senescence and the telomeres are shortened 
each time the cell replicates.  It would seem likely therefor that other 
changes, in the genes and/or their expression, may be occurring as well.

>> Still, studies may show different genetic expression between young and old
>> cells in the absence of the senescent state. (Although my brief Medline
>> search couldn't come up with any, that is more a lack of knowing where to
>> look rather than a lack of studies.)  
>Actually I think it is a lack of studies.  The number of
>genes that we have information on is so small (relative to
>the number of total genes) that we really don't know what is
>going on at this point.

That would explain it.  As you note below, most of the research has been on 
observed changes in functioning.  Since no significant changes are noted 
during this period there not much interest in investigating it.

>Also bear in mind that the studies that do exist are studies
>that are grabbing the low-hanging fruit.  To think that the
>majority of genes are going to have the same type of
>expression pattern changes as the genes that we currently
>know about may be completely wrong.  It seems quite possible
>to me that the only reason the genes that we know change
>with aging were found was because they change dramatically
>and so are easy to spot with techniques such as differential
>display or subtractive hybridization.  There could be
>hundreds or thousands of smaller perturbations in gene
>expression, going up, going down, or oscillating, starting
>right after terminal differentiation, that are very
>important, but we simply have not spotted them because the
>technology to do so is only coming of age right now.

I agree.  The technological techniques for this and other scientific 
investigations, like the ability to detect senescent cells noted in my 
earlier post, are just now becoming available.

The techniques you are working on, James, may help us better understand what 
is going on in genetic expression in a wide range of situations.  I look 
forward to seeing some of your results.

Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.

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