From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Fri Apr 28 2000 - 14:15:22 MDT
Blech, phooey.... The Reuters piece is a classic example of good
science getting munged by the press. I've commented appropriately
on some of the excesses the press may have solicited from the
authors and would encourage the authors to put a little less "spin"
on their work in the future. The last thing the field of anti-aging
research needs is to build a history of excessive claims by scientists.
On Fri, 28 Apr 2000, Doug Skrecky posted a copy of a Cryonet message #13652:
> CryoNet - Fri 28 Apr 2000; From: Jan Coetzee
>
> Report: Cloning Produces Unnaturally Young Cattle
>
> By Maggie Fox, Health and Science Correspondent
> WASHINGTON (Reuters) -
Could one of our super-sleuths come up with an Email address for Maggie?
She could use a copy of this.
> Scientists who cloned six cows said on Thursday the animals show
> signs of being even younger than their chronological ages, and said this
> could mean cloning technology offers a true fountain of youth.
Crap, absolute crap. What is the meaning of "younger"?
What the Science article says is "Extension of cell life-span...".
Even that term is misleading because strictly speaking, the "life-span"
of a cell is how long the cell lives. The article should have said
"Extension of cellular replication capability...".
Sloppy work on the part of the Science editors.
Recent publications have called into question the early simplistic
assumptions regarding telomere length and aging. For example
see: Modello, C. et al, "Telemere length in fibroblasts and blood cells
from healthy centenarians". Exp. Cell Res 1999 10;248(1):234-42.
> The cloning process seemed to have literally turned back the aging clock
> in the cells of the six heifers.
Since there is no clear scientific picture of cellular aging at a
molecular level (only early hints of how gene expression may change),
and a couple of marker genes (e.g. Campisi's work) it is excessive to
claim the aging clock has been turned back. The article abstract cites
the measurement of one gene only (EPC-1).
>
> The researchers said it might be possible to use cloning to create organs
> that are nearly immortal for use in transplants, or tissue lines to treat
> diseases of aging such as Alzheimer's, arthritis and heart disease.
How? Treating Alzheimer's with a "cloned" brain, arthritis with
cloned joints and heart disease with meters of cloned blood vessels?.
Claims in these areas should stick with examples where we have known
applications for "cell-replacement" (not organ-replacement).
Parkinson's treatments or repopulation of the immune system after
chemotherapy to treat leukemia would be better choices for possible
applications.
>
> ``Not only were we able to clone calves ... but these animals appear to
> have cells younger than their chronological age,'' Robert Lanza of
> Advanced Cell Technology, Inc., who led the study, said in a telephone
> interview.
Only if you assume telomere length is a measure of chronological age.
This statement is like saying a decrease in accumulated DNA mutations
or protein glycosylation results in "younger" cells. Aging is a
multifactorial process. Only when the complete measurement of *all*
the aging related biomarkers is feasible and the work done by ACT
demonstrates that their work impacts *all* of them, should they make
claims regarding clones having "younger" cells. The accurate statement
would be that the cells have "increased replicative potential and
show indications of gene expression patterns typical of 'younger'
cells".
>
> Clock Gets Reset
>
> ``What we showed in this paper is this clock gets reset. It gets wound
> back up,'' said Dr. Michael West, president and chief executive officer
> of the Worcester, Massachusetts-based company. ``It remains to be
> determined whether this would extend the life of the animal.''
The jury is still out on whether telomeres represent "a clock".
West at least makes an appropriately conservative statement
regarding animal longevity.
>
> The findings, published in the journal Science, are surprising because
> the most famous cloned animal, Dolly the sheep, appears to be older than
> her chronological age.
Again we have people equating telomere length and "age"!
Anyone who understands the mechanism by which telomerase acts would
understand that should be able (in theory) to reset telomeres length
to a juvenile state or even longer. The article indicates that their
results "could be due to species differences and/or differences in
nuclear transfer techniques or donor cell types".
So, they have confirmed what one would have expected but don't know
how they did it...
>
> When they are frayed beyond repair, the cell dies. This stage is known
> as senescence.
This is simply wrong. The cells *DO NOT DIE*. They simply cease
to replicate.
>
> Dolly had old telomeres. But the six heifers, cloned from cells taken
> from a 45-day-old fetus, have exceptionally young telomeres.
Better would be the terms "long" and "short", not "old" and "young".
>
> ``The egg cells acts like a little time machine and can take it back, as
> far as we can tell, to the beginning of life,'' West said.
Fine, I can accept that. There has to be a mechanism for reglating
the activity of telomerase in germ cells.
>
> ``It's the first day in a new era in treating age-related disease,''
> West said.
A tad extreme, particularly given that they don't know how they
produced the effect.
>
> ``If you had a damaged heart, we could take a few cells from you and
> grow up new heart cells and these would be your own cells so you
> wouldn't reject them,'' added Lanza.
I know of no work that uses muscle "grafts" onto a heart to strengthen it.
Far better would be the growth of a new heart, and we are a long way
from that until we completely understand the regulatory processes
in complex organ development and someone has demonstrated control
over those processes in the lab. We can do skin and a few other
organs today, but we are far from growing organs that have complex
cellular or physiological architectures.
> Of course, this would involve technically cloning the patient --
> something called therapeutic cloning -- and there would be opposition
> to allowing it.
This doesn't involve cloning the whole patient, it involves growing
new organs from the patient's cells. Once telomerase regulation
is understood, it should be possible to lengthen the telomeres
*without* going through a cloning process. Cloning is a rather
expensive and unnecessary process [1896 oocytes used, 87 positives
(5%) after just the first step].
>
> Lanza said his team does not quite understand how the heifers became
> ``younger''. But he said genes whose activity usually dies down as a
> cell ages were especially active.
>
> ``These results suggest the animals are younger than their biological
> age,'' Lanza said.
>
This would be interesting, because it could imply some type of switch
or imprinting that could keep telomerase (or other "youth promoting"
genes) active longer. It is going to be interesting to see how this
relates to the CR work and theories that sexual maturity shifts
resources from maintenence and repair into reproduction. If they
have accidentally stumbled on a switch for youthful maintenence and
can understand what they did, then it really would be a breakthrough.
> ``When other cows the same age start to grow old and frail, their cells
> should be able to divide the same as a newborn calf's. They should be able
> to repair damage due to disease and aging and should live longer,
> healthier lives.
The results are only going to impact tissues with dividing cells.
Accumulated damage and death of non-dividing cells will be unaffected.
>
> Only time will tell. Cows allowed to lead natural lives live to be 24
> and older.
So anyone over 60 will likely be dead before we know for sure...
The URL for the original Science article is:
http://www.sciencemag.org/cgi/content/full/288/5466/665
Robert
P.S. Doug, could you repost this to CryoNet (or tell me how to do it)?
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