Reply to: RE>>How many cells are needed?
I think these discussions need to be put in the context of cell biology =
and the biology of cell aging to be informative. First, on the cell =
biology side, cell turnover in areas like blood cells do not involve a =
large amount of cell division of the most primative bone marrow stem =
cell, the large number of division occurs downstream. The bone marrow =
stem cell itself rarely divides, and appears to be losing telomeres at a =
rate similar to a telomerase negative cell, and indeed, approaching the =
Hayflick limit at about 100 years (PBLs that is). This could cause =
immune problems in advance of the whole population of PBS being =
stone-cold senescent because, of course, individual clones of cells =
needed to recognize particular antigens may be impeded in fighting an =
acute infection leading to serious disease or death.
In a similar way, just a few fibroblasts (for instance) that are =
senescent could lead to aging of connective tissues. Senescent cells =
are abnormal not only in the fact that they have ceased cell division, =
but also in that they are locked into a constitutive activated state in =
regard to secreted protein expression. For example, senescent =
fibroblasts secrete about 50X the normal level of collagenase which =
"acts at a distance" destroying collagen not only in the immediate =
vicinity of the senescent cell, but throughout the tissue.
So, the thought here is that a few senescent cells can lead to =
histopathology and age-related (time dependent) decline in morpholysis =
and physiolysis. It may be inappropriate to ask, where does the whole =
population of cells lose proliferative capacity.
-MWest
--------------------------------------
Date: 9/16/97 7:02 AM
To: Mike West
From: DawnC at bigfoot.com
I believe it's generally accepted that, even by age 100, our cells still
have enough telomeres to divide. Furthermore, as you know, cells can
reach a state of quiescence where they don't divide but still carry out
their normal functions.
So, while Telomere shortening is involved with aging, I don't think it's
the MAIN reason why we live 75-100 years.
Suresh Rattan wrote:
>> While teaching a course on biogerontology I have got stuck with this
> question: how many cells are needed to live a life of 100 years?
> The background for this question is that for the last 35 years the =
dominant
> paradigm in cellular ageing research is that normal diploid cells have =
a
> limited division potential, known as the Hayflick limit, which for =
human
> beings is about 50 to 70 doublings, depending upon the age of the =
donor,
> cell type etc etc etc. Therefore, even if one considers the first =
normal
> diploid cell, the zygote, having a Hayflick limit of, say 70, then it =
can
> potentially give rise to 10 to the power 21 (I cannot type superscript =
on
> this e-mail format!!); that is 1 followed by 21 zeroes number of =
cells. Is
> this number sufficient to take us through life?
> 1: The answer papears to be YES if you calculate this (highly highly
> simplified/simplistic) way: The protein weight of a single cell is =
about
> 250 pigogram; so a 100 Kg person will have about 10 raised to the =
power 14
> cells; even if 100% of the cells have to be replaced everyday for 100
> years, one needs a total of 10 to the power 19 cells maximally; thus
> thepresent estimates of the Hayflick limit provide enough cells to =
live.
> 2: The answer appears to be NO if you calculate in another way (the =
way
> Harry Rubin has done in his recent critical review of in vitro versus =
in
> vivo ageing, published in the Mechansism of Ageing and Development, =
vol.
> 98; pp. 1-35; 1997): take an example of epidermal layer of the skin; =
basal
> cells have to divide once every 10 days or so for the regular
> differentiation and turnover of keratinocytes; so in a year they have =
to
> divide about 36 times, and in 100 years, about 3600 times; the same =
may be
> the case for other dividing cell populations (RBC turnover time about =
3
> times a year, so about 300 times in 100 years, and so on. Considering =
this
> way, the present estimates of the Hayflick limit are too low to be
> meaningful in real terms.
> So, what is correct? Even if we consider that normal diploid cells =
have a
> limit, how much it is and is it relevant to ageing? Or there is no =
limit
> like that in the body, and all that stuff which people have been doing =
for
> the last 35 years with respect to finding regulatrors of proliferative
> capacity is crap?
--
-Dawn-
Time is the best teacher. Unfortunately, it kills all of its students.
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To: ageing at net.bio.net
From: Dawn <DawnC at bigfoot.com>
Subject: Re: How many cells are needed?
Date: Tue, 16 Sep 1997 08:29:33 -0500
Message-ID: <341E89BD.16DF at bigfoot.com>
Reply-To: DawnC at bigfoot.com
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To: Suresh Rattan <rattan at imsb.au.dk>
