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November 20, 2002
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Aging and
Disease
Infections can fell you at any age
It's clear that certain diseases--most notably infectious
diseases--aren't directly related to aging but can assail you at any age.
Vibrant youth is no surety against fulminating infections.
It's also clear that other (degenerative) diseases must
necessarily be exacerbated by aging.
Preventing cardiovascular disease means preventing your
veins and arteries from aging.
For example, the stiffening of arteries and of the heart with
advancing age raises blood pressure and reduces the pumping capacities of the
heart. Treating this requires the softening or de-polymerization of connective
tissues. But this stiffening of connective tissue is part of what causes other,
visible symbols of aging such as wrinkles and sagging skin. Softening veins,
arteries and the heart would have, as a side effect, the amelioration of the
cosmetic stigmata of aging. It would make you look younger.
Preventing cancer entails preventing cells from aging
Cancer is also exacerbated by aging. As cells approach their
Hayflick limits, the probability of cancer rises rapidly.
On the other hand, if you could back up cellular ages, as, to
a certain limited extent, you can with retin-A, you might move cells farther
from a malignant transformation. But at the same time, you would be restoring
cells to a more youthful condition. In other words, if you completely prevented
cancer, you would be preventing cells from growing old and functioning
improperly. .
Alzheimer's and Parkinson's Diseases might be prevented
by preventing aging
Like cancer and cardiovascular disease, AD and PD tend to be
diseases of old age. You don't see a lot of AD and PD among twenty-year-olds. AD
and PD also appear to have some relationship with cerebrovascular competence.
The bottom line is that is we manage to
cure degenerative diseases, we'll have gone a long way toward curing the
degenerative disease that's known as aging.
I know I've said this before,
but it's becoming more apparent how true this is. You can't separate aging
remediation from the alleviation of degenerative diseases.
Worrying about the consequences of life extension may
be a laugh for the next fifty years
I can't resist another comment about life extension. In all
likelihood, concerns about what's going to happen when we conquer aging are in
the same league with concerns in 1952 about what was going to happen in the
1960's and 1970's when robots took over the world. Much as I wish it were
otherwise, the conquest of aging may not be a burning issue for the next x
years.
Some candidate worries for highly motivated worriers
For anyone who's looking for something to worry about, how about
worrying about runaway global warming, as peat bogs, methane ice, and other
carbon dioxide and methane reservoirs warm slightly and begin to outgas? Or how
about worrying about robots taking over? Were getting closer. Or how about an
artificial intelligence that somehow takes over the Internet? How about some of
our brightest people taking "smart drugs" as they become available,
and, waxing incredibly intelligent, take over the world? (Of course, you might
argue that anyone's who has two brain cells to click together wouldn't want the
job.)
"Immortal"
Skin
Dr. Lynn Allen-Hoffmann's "immortal"
skin
In 1995, Sandy Schlosser, the lab manager for Dr. Lynn
Allen-Hoffmann's laboratory at the University of Wisconsin Medical School,
noticed some living skin cells among a colony of dead skin cells that she was
throwing away. Normally, skin cells last about 15 weeks in vitro, and then die.
Ms. Sclosser held the Petri dish to the light and said, "Hey, Lynn, what
the heck is this?" Dr. Allen-Hoffmann had no idea. "Oh gosh, maybe
it's a long-lived variant. Let's just keep it and see what happens." They
did, and the
skin cells never stopped growing ("Immortal Skin", Popular
Science, August, 2001, pg.58).
That was seven years ago, and the skin cells are still
dividing, and are still normal skin cells... with one exception: they're
not dying of old age.
Geron Corporation's "immortalized"
tissue products
In the meantime, Geron
Corporation is currently marketing "immortal"
cell lines for research purposes. Geron achieves this extension of
proliferative capability by transfecting normal human tissue cells with the
human telomerase gene, permitting them to replicate indefinitely.
Interestingly, cells taken from diseased tissues can also be
"immortalized", allowing diseased tissues to be studied. In other
words, "immortalization" does not bring about the elimination of
inheritable defects, but apparently, only evades the Hayflick limit.
Do these immortalized tissues age in other
respects?
One interesting question would be: do these tissues age in
terms of other age markers such as lipofucsins? It might be that
"immortalized" cells that are continuing to divide would, during
mitosis, split lipofucsins between the parent cell and the daughter cell, thus
continually diluting the lipofucsin content of the dividing cells. However, the
same argument could be made regarding normal skin cells. However, we know that
these do eventually build up high levels of lipofucsin deposits in spite
of their continuing replication.
What about the HeLa cancer cell culture?
Of course, "immortalized" skin cultures haven't
been around for 80 or 90 years. Possibly, they would also age after enough time
has passed. (One clue to this might lie in the HeLa (Henrietta
Lacks) cancer cell culture, which is still going strong after 50
years.)
Can an animal be "immortalized" by
transfecting it with the telomerase gene?
One thought that comes to mind: if someone were to be
telomerase-enabled at age 20 or age 30, would her or his age be arrested at that
point? What would happen if this were attempted with an animal model? Has it
already been tried with animals?
A very important consideration is that, in vivo, human skin
cells produce their own telomerase. For some reason, this must not operate when
skin cells are cultured. Would transfecting skin cells with a telomerase gene
change anything?
Might transfection with the telomerase gene
trigger latent malignancies in animals?
One cause for caution in this is the possibility that
telomerase, administered to an animal, might immortalize damaged cells that
become malignant. (One would expect that this would have been tried in animals
by now.)
I could imagine that the fact that malignant cells haven't
turned up in "immortalized" cells may not say much about their
resistance to malignant transformations. The human body contains about 50
kilograms of tissue (10 trillion cells), and even then, milignancies may not
occur over the course of a lifetime. For a billion cells, the chance of
developing cancer over the course of a hundred years would be negligible. (Of
course, tissue cultures don't have the benefits of an immune system to add to
their cancer protection.)
I've
enclosed the term "immortal" in quotes because only death and taxes
last forever.
Blue Gene and
ASCI Purple
About two years ago, I reported plans for IBM's Blue Gene, a
petaflops computer. A petaflops is 1015 floating point operations per second, or
several hundred thousand times as fast as today's fastest desktop computers.
Today, there have been announcements updating the plans for Blue Gene, and
another IBM supercomputer called ASCI Purple (An Incredible Calculator).
IBM expects to deliver a 360-teraflops version of Blue Gene to the Livermore
Radiation Laboratory by 2005 (Supercomputer speed race on again).
IBM will also produce a 100-teraflops computer known as ASCI Purple which is
advertised as matching the speed of the human brain. (Evidently, someone is
taking Dr. Hans Moravec's speed of 100 teraflops as the speed of operation of
the human brain.) And as all of this makes fresh headlines, "The Cell"
is presumably ticking away, waiting for its bombshell 2005 debut (IBM, Sony, Toshiba team on processor architecture for broadband).
In the meantime, Cray Computer has announced plans for a
petaflops computer by 2010 (Cray fills need for computer speed).
It wouldn't seem impossible to find teraflops computing
speeds in linked desktop computers by 2010, especially if special-purpose chips
sets were available. Matrox had a seven-board, 100-gigops graphics processor on
the market several years ago. Reportedly, nVidia has a one-terops graphics card
available now.
Human-brain processing speeds are getting closer.
Disk Storage
Capacities
The National Storage Industry Consortium has set a goal
of dsk drives that can store one terabit per square inch by 2006. That would
enable 3-to-4 terabyte, 3.5" disk drives by 2006, in keeping with the
doubling-every-year capacity increases that have characterized disk drives for
the past decade. NIST has awarded Seagate a $21,000,000, 5-year research
contract to develop disk storage techniques that will increase disk storage
capacities by a fact or 100 or more, eventually allowing, perhaps, 20-or-more
terabytes to be stored on a 3.5" disk drive. Impressive as are these
numbers, it is perhaps worth mentioning that the human brain, with 1015
synapses, might store something like 1,000 terabytes of information. Of course,
the brain is constructed of unreliable components, and may require redundancy to
a degree that isn't necessary in computers. In that case, 200 terabytes might be
a more realistic estimate of the brain's storage capacity. (My estimates are
very uncertain.) By 2010, 200 terabytes might be achievable with 10 20-terabyte
disk drives. And by 2014, that number might shrink to one or two disk drives.