"We are on the verge of a revolution in medicine: understanding, treating, and ultimately preventing the causes of degenerative aging. But medical revolutions only happen if we all stand up in support of funding and research. We did it for cancer. We're doing it for Alzheimer's. We can do it for aging - and create an era of longer, healthier lives!"

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  • Monday, June 12, 2006

    "Anti-Aging Molecule" and the Need to Read Behind the News

    You just can't follow science through the mainstream media alone; the Korea Times provides an excellent demonstration today as to why this is the case:

    "All cells face an inevitable death as they age. On this path, cells became lethargic and in the end stop dividing but we witnessed that CGK733 can block the process," Kim said.

    "We also found the synthetic compound can reverse aging, by revitalizing already-lethargic cells. Theoretically, this can give youth to the elderly via rejuvenating cells," the 41-year-old said.

    Kim expected that the CGK733-empowered drugs that keep cells youthful far beyond their normal life span would be commercialized in less than 10 years.

    Where to start on this? My suspicion is that a reporter was entirely caught up a confusion between cellular senescence and degenerative aging in people. These are two very different things, but terms like senescence and aging - meaning "degenerative aging" in common usage - have a range of more precise meanings in scientific circles:

    Cellular senescence is the phenomenon where cells lose the ability to divide. In response to DNA damage (including shortened telomeres) cells either senesce or self-destruct (apoptosis) if the damage cannot be repaired. Organismal senescence is the aging of whole organisms. The term aging has become so commonly equated with senescence that the terms will be used interchangeably in this article.

    It might not even be the reporter who slipped up, but rather a translator; the article makes much more sense and is far less sensational if you replace "aging" with "cellular senescence" throughout.

    If you backtrack to the actual scientific paper, you'll find some interesting work on uncovering and manipulating the cellular mechanisms of senescence:

    Most somatic cells encounter an inevitable destiny, senescence. Little progress has been made in identifying small molecules that extend the finite lifespan of normal human cells. Here we show that the intrinsic 'senescence clock' can be reset in a reversible manner by selective modulation of the ataxia telangiectasia-mutated (ATM) protein and ATM- and Rad3-related (ATR) protein with a small molecule, CGK733.

    This is a proof of the capabilities of a fairly new system that allows far more effective and efficient insight into the workings of a cell than was possible even just a few years ago:

    Kim basked in global recognition last June when he and his associates developed a technology dubbed MAGIC, short for magnetism-based interactive capture.

    MAGIC uses fluorescent materials to check whether any drug can mix with targeted proteins inside the cell. The results were globally recognized by being printed by the U.S.-based journal Science at the time.

    "MAGIC is kind of a source technology to see inside cells. Based on the method, we also found a pair of promising substances that can deal with cancers," Kim said.

    Biotechnology marches ever onwards! By any standards, this is good science and very useful technology - but I don't see it as an immediate, direct step towards extended healthy life spans. Let me explain: an accumulation of senescence cells is a part of the aging process, and is quite possibly directly harmful in addition to cluttering up the body with inactive or oddly active tissue.

    The second type of supernumerary cells, senescent cells, accumulate in quite large numbers in one tissue, the cartilage in our joints. They also accumulate elsewhere, but in much smaller numbers; however, these may still be important by being actively toxic. They aren't able to divide when they should, and they also secrete abnormally large amounts of some proteins.

    However, cellular senescence serves at least one essential purpose in the body: it protects against cancer that results from age-damaged cells.

    "Cellular senescence is considered an essential contributor to the aging process and has been shown to be an important tumor suppression mechanism. In addition, emerging evidence suggests that senescence may also be involved in the pathogenesis of stem cell dysfunction and chronic human diseases. Under these circumstances cells undergo stress-induced premature senescence, which has several specific features." As this review paper points out, developing a technology to turn off programmed senescence would simply result in much more cancer - the process serves an important purpose in shutting down potentially dangerous cells. The problem needs a better solution, more likely focused on convincing the body to recycle these cells rather than leaving them to degrade the performance of tissue.

    Simply turning off or reversing cellular senescence is an impressive technology demonstration and teaches us more about cellular biochemistry, but it doesn't appear to me to the foundation for a viable anti-aging therapy.

    As a last note, and while we're on the subject, I should point out this timely item from Medical News Today:

    "Unless journalists are careful to provide basic study facts and highlight limitations the public may be misled about the meaning, importance and validity of the research", said Woloshin. For their study, the team analyzed newspaper, TV and radio stories that appeared in the US for research reports from five major scientific meetings in 2002 and 2003 to see if basic study facts (eg., size, design) were reported; whether cautions about inherent study weaknesses were noted; and if the news stories were clear about the preliminary stage of the research.

    The researchers found that basic study facts were often missing. For example, a third of reports failed to mention study size; 40% did not quantify the main result at all.

    Important study limitations were often missing. For example, only 6% (1/17) of the news stories about animal studies noted that results might not apply to humans. And only 2 of 175 stories about unpublished studies noted that the study was unpublished. Schwartz and Woloshin, who frequently present to the media on how to understand and accurately report research results, say that while reporters can and should do better, another reason for misinterpreted or "over-hyped" research is its early release at professional meetings that reporters are encouraged to attend.

    Food for thought, no? In this day and age of a searchable internet, there's no excuse for not getting out there to verify that a reporter knows what they're talking about. A simple internet connection gives you more power than the entire research department of a 1970s major news organization - make use of it!

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    Posted by: Harold Brenner at June 13, 2006 3:41 AM

    There are three important take home messages in this discovery:

    1. Senescence is reversible
    2. DNA damage induces senescence
    3. Rather than interfering with the DNA damage signaling pathway we should be looking at increasing the rate and ability to repair DNA damage to bring about the reversal of senescence.

    [Posted by: Harold Brenner at June 13, 2006 3:41 AM]

    Posted by: Toog at June 18, 2006 4:45 PM

    There are many biological technologies that are advancing at a rate similiar to what has been seen in computing.

    http://futurist.typepad.com/my_weblog/2006/03/are_you_prepare.html

    Living to 100 will be common for most us us alive today.

    [Posted by: Toog at June 18, 2006 4:45 PM]

    Posted by: Nostradamus at June 18, 2006 5:48 PM

    I cannot vouch for this theory of aging, but my Sister is an M.D., and claims that aging can never be "reversed", in a way most people can understand. First, she says, only in very rare instances can a man live over the age of 100. She said that she's performed almost 200 necropsies on men, and has never seen a man over the age of 75 that did not some evidence of prostate cancer. Prostate cancer is a slow killer, but live long enough and it will certainly kill you. Second, she says that cells make reproductions of themselves, but not "exact" ones. It's similar to putting a picture into a copy-machine and reproducing it. The copy looks just like the original. You can't tell the difference. But take that copy and make a copy of it, then that 3rd copy and repeat the process over and over, you will find that gradually the quality of the reproductions get so bad that they're useless. That's why skin cells wrinkle, blood vessels collapse, hair greys, and eventually cell damage is never repaired. Chemicals speed up the damage as well as hinder proper reproduction. But even if one lived a "Pure" life (clean water, wholesome food, lack of infection or injury, ect.)still that reproductive error rate will eventually cause failure, as DNA becomes frought with errors. She thinks we've just about extended life as long as it's going to be extended, save the ability for mass organ transplant or mechanical replacement. And you can't replace a brain. Not yet, anyway. Funny how this theory tends to support "Intelligent Design" to some extent. And you didn't think the Lord had a sense of humor????

    [Posted by: Nostradamus at June 18, 2006 5:48 PM]

    Posted by: Reason at June 18, 2006 6:00 PM

    I strongly suggest you visit the Strategies for Engineered Negligible Senescence (SENS) website for a suggested approach to repairing/reversing aging, based on what scientists know today.

    http://www.sens.org

    Progress is, by definition, the process of making new and better things a reality - such as repair strategies for the many modes of age-related cellular damage.

    [Posted by: Reason at June 18, 2006 6:00 PM]

    Posted by: James at June 18, 2006 8:00 PM

    Sorry Nostradamus, but cells do not fail because of "replicative fading" (which is a science fiction concept, btw) They fail because of the accumulation of damage. I'm afraid your sister is wrong, or perhaps pulling your leg.

    If we accept your sister's hypothesis as true for a moment, then by the 3rd and 4th replications, you would effectively be aged, as the body replaces all cells over a 10 year period, approximately. We should all therefore be at death's door by our mid 30's or 40's at most.

    As for your last point, I would suggest to you that a system that cannot be repaired or rejuvenated is an example of "Unintelligent Design". I'd expect better from such a powerful Deity :)

    You really should take Reason up on his suggestion to check out www.sens.org, there's a wealth of accurate scientific information there. You should probably direct your Sister there, too.

    Regards,

    [Posted by: James at June 18, 2006 8:00 PM]

    Posted by: Hugh Bristic at June 20, 2006 6:33 AM

    I can't find the original Nature article anymore, but when I looked through it originally, I thought it said that the rejuvenation also reversed genetic damage in cells. I could be misremembering, but it might be worth taking another look to make sure.

    [Posted by: Hugh Bristic at June 20, 2006 6:33 AM]

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