Cristofalo Study [was Senescence and Crisis: Whats the difference?]

Excelife excelife at
Sat Oct 17 10:51:43 EST 1998

Re: Cristofalo VJ, Proc Natl Acad Sci U S A 1998 Sep 1;95(18):10614-9

"Relationship between donor age and the replicative lifespan of human cells
in culture: a reevaluation."

>> Without data on telomeric length and a selection process that could skew
>> the results you're going to have to come up with some better studies to
>> show fibroblasts do not senescence in the elderly.
>Tom, you must be a great deal more careful with your logic before you
>challenge the findings of respected specialists like Cristofalo and Allen.
>This question has nothing whatsoever to do with the history of the line,
>only to do with its future (how it behaves after isolation from the donor).
>You're suggesting that the cells isolated from older donors had shorter
>telomeres than those from younger donors

Quite the contrary, by selecting only "healthy" people for the study their 
telomeric length was probably pretty similar regardless of age.  (Just a 
quick note; Dr. V.J. Cristofalo is well respected and carries no bias to his 
research.  But he still should have tested for telomeric length.) 

>Now, I would have been less surprised if you'd said that the selection
>of donors skewed BOTH the telomere length and the replicative capacity,
>such that the (perhaps unusually healthy) older donors has on average
>the same length telomeres (hence replicative capacity) as younger ones.
>That's admissible -- "all" you have to do is square it with the finding
>that health does not confer indefinite lifespan.

That was my suggestion, which I may not have made clear, and without data on 
telomeric length from the study we don't know if it's accurate or not.

>We are talking about the in vivo case (relevance of donor age), so the
>first citation is the only one with any relevance.  It is a small study
>dating from 1985.  I haven't read the paper, only the abstract, but I
>submit that if you are willing to take that in preference to a large,
>recent and sophisticated study from Cristofalo, not to mention Harley's
>revised interpretation of Allsopp 1992 (which is of course directly in
>line with Cristofalo et al), then you are not following your own maxim:
>"If the facts don't fit the theory you change the theory not the facts".

(I don't recognize your reference to Harley's new interpretation of Allsopp 
and would like to review it if you have the reference.)

I do agree with the maxim posted above and evidence is mounting that there is 
a difference between in vitro and in vivo aging, at least in some 
fibroblasts. Analyzing and interpreting these results is one of the reasons 
we're having this discussion and why I referenced Critofolos' paper in the 
first place.

A paper by Takeda K,, (J Cell Physiol 1992 Dec;153(3):450-9, "Similar, 
but not identical, modulation of expression of extracellular matrix 
components during in vitro and in vivo aging of human skin fibroblasts.", 
delineates some of these differences.

Whether there is a difference in telomeric maintenance and shortening in 
these cells over time is an issue that needs to be explored.

Thomas Mahoney, Pres.
Lifeline Laboratories, Inc. 

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