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November 20, 2002

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Longevity Index


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.