Hello Mike,
Given that senescent fibroblast produce such large amounts of
collagenase, are collagenase inhibitors indicated for such
symptoms of aging such as sagging skin, arthritis, periodontal
disease, etc... ?
Regards,
Lou Pagnucco
"Mike West" <mwest at geron.com> wrote in article
<n1337706559.37463 at geron.com>...
> 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>
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> To: Suresh Rattan <rattan at imsb.au.dk>
>>>>
