Via Ouroboros and a few other places, I note that the open-access journal PLoS Genetics has started off on a series of reviews and opinion pieces on aging science.

An Age-Old Problem

In keeping with the mission statement of our journal to present interdisciplinary research in the broadest possible context, we have commissioned a series of Review and Opinion articles bound thematically to a discrete set of topics of inherent complexity, as well as broad interest. Each component of the series will examine a facet of the chosen problem and we hope that the amalgam of each series, which will be available electronically as a unified entity, will both educate the non-specialist as well as provide a balanced view that will transmit to our readership an appreciation of the progress made and the future trends in each field.

Our inaugural series focuses on aging, a field under both rapid evolution and substantial controversy.

Yes indeed - though the focus here skirts around the most interesting controversy of all, that surrounding the moral imperative to apply scientific knowledge to treat, repair and otherwise cure aging as soon as possible. There is considerable controversy and ongoing change within and surrounding the gerontology community on topics such as the potential timescales of extending healthy longevity, and whether that goal should be the focus of research.

(My point of view: what is the point of researching a field of medicine that relates to great suffering, pain and death if not to as rapidly as possible use that knowledge to prevent that suffering, pain and death? Aging is no different from cancer or AIDS in that respect, and you don't hear many voices within the cancer research community advocating a "look but don't touch" philosophy of science).

The first review in the series is a topic long-time readers might be familiar with; an examination of the nuts and bolts of the mitochondrial free radical theory of aging, such as it is understood today.

The Role of Mitochondrial DNA Mutations in Mammalian Aging

The mitochondrial theory of aging is based on the premise that reactive oxygen species (ROS), generated throughout the lifespan of an organism, damage mitochondrial macromolecules, including proteins, lipids, and mtDNA. Although most molecular damage is reversible through repair or molecular turnover mechanisms, unrepaired DNA damage may lead to mutations that accumulate as a function of age. The accumulation of mutations ultimately leads to permanent age-related mitochondrial dysfunction, which contributes to the aging phenotype.

The precise nature of the details are still being debated; the plausible scenario put forward by biomedical gerontologist Aubrey de Grey a few years back (and explained for the layman in a past post here at Fight Aging!) is still not an open and shut case at this time. Bulletproof analysis of the evolution of very complex biochemical systems across years and decades of time is still a little beyond present day capabilities - but not for too much longer. If I had to throw a date into the ring, I'd suggest we should be looking for final settlement of the details of the mitochondrial free radical theory of aging no later than 2012.

That said, I suspect research teams will be entering clinical trials for therapies for the repair and replacement of damaged mitochondria en mass in the body somewhat in advance of that date. That feat has already been demonstrated in animals, and the pace of research is blistering these days.

Technorati tags: aging, gerontology, medical research, mitochondria

Posted by Reason at 8:59 PM
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As noted over at the Methuselah Foundation blog, the Foundation technology volunteers have enabled group memberships in The Three Hundred:

For the price of a cup of coffee per day, would you like to join a select group of humanitarians who will be remembered for their vision and saving millions of lives?

Modern medical science continues to show us that the aging process may no longer be the intractable problem it has been perceived to be for every generation preceding ours. There is a present need to move faster towards a previously unattainable goal: the control of aging. This need for more rapid medical progess is only magnified by the current profound lack of funding for aging research. Funding springs, at root, from widespread public awareness of advances and possibilities in aging research. Educating the public is an essential step in moving philanthropists and governments to allocate more resources to the study of aging. The problems caused by aging leave us poor in body, spirit, and finances. We must step forward to tackle them!

...

What's it worth to you to live 150 healthy years? What's it worth to you to raise the average human lifespan to 150 years, just as a start? These are not idle questions! Membership of The Three Hundred is a meaningful but affordable commitment: $1,000 a year, by the end of each year, for 25 years. This amounts to $85 a month or $2.75 a day, the equivalent of a visit to Starbucks.

I and many others in the healthy life extension community have joined The Three Hundred in the fast few years order to meaningfully influence the future of longevity research - these funds go to the Mprize for anti-aging research, and the SENS research funded by the Methuselah Foundation. But if you don't want to take on a place in The Three Hundred by yourself, why not band together with your friends and share in the knowledge that you are helping to advance the healthy life extension cause?

For an examination of why everyone should step up and contribute to the growth of the Methuselah Foundation and success of its initiatives, I turn to an essay by Michael Rae:

While I am still relatively young and believe that I am indeed aging more slower than those around me, I have suffered the loss of my loved ones to the aging process already. It's bad enough to watch allegedly "independently-living" aged strangers out in public, idly shuffling their feet, pushing cleverly designed wheeled walkers or balancing on their canes, unable to open the doors for themselves, faces a mask of apathy. It's much worse to spend even a few minutes in a nursing home, walking out of a world of relative health of body and mind into an asylum of decay: men and women, once fit and optimistic about the future, now tied to oxygen tanks, raving mad or sunk into almost complete retreat from the outside world, sitting down hours in advance of their meals for lack of any better purpose to their lives, needing help to get out of bed or clean their own wastes.

...

We need an intervention that will fundamentally arrest, or reverse, the biological decay that creeps into our every cell with each passing year. Too few people are pushing this agenda. We - the healthy life extension community - must put our hands upon the wheel. If not us, who else, after all?

The first group membership has been opened by Parish Mozdzierz for the Betterhumans community; what will your group be?

Technorati tags: activism, life extension

Posted by Reason at 9:19 PM
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I'm very much in favor of folk who step up and inspire people to get things done: all sweeping changes start with a single act, and the world can be changed greatly if a million people each contribute one small but meaningful action to the whole. So I'm pleased to see people itching to get started and make a difference to the future of healthy life extension technology over at the Immortality Institute:

27 May - 2 June : The world will be introduced to the concept of longevity, and healthy lifespan extension.

It will be done by simply having every available member of ImmInst subscribing to this thread, following this thread, participating in this thread, and achieving the goals of this thread so that between those dates every single member who has participated will be mobilised to post between 10 and 20 flyers in very public places in their local area. Inexpensive, easy, effective.

It is late February. I am arbitrarily designating 1 month to discussion time, 1 month to flyer design, and 1 month to movement organisation. 3 months maximum. The date I am picking then is the week from 27 May 2007 - 2 June 2007. In that week I intend to have every single member of ImmInst who is functionally capable of doing so, to have printed themselves a number of "Awareness Raising Flyers" and to then post these flyers to strategic points in their local city, suburb, town, village, workplace, university, bus stop and any other place they can get to.

Simple and to the point - a clearly defined goal that everyone can help accomplish. Very good. The discussion thread and flier design thread are both active, so jump on in and show your support!

As I often repeat here, the future is a matter of what you make of it, and the greatest hurdle to the rapid development of medical technologies to greatly extend the healthy human life span is the absence of widespread support and understanding for such a goal. That is a problem everyone can help with - you don't have to be a scientist or wealthy to reach out and educate a couple of people on the real prospects for progress towards greater longevity. If our future is one of frailty, suffering and death, it will be because we have failed to convince our fellows of the plausibility and merits of working towards a cure for aging.

Technorati tags: activism, life extension

Posted by Reason at 8:40 PM
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A group of the regulars over at the Immortality Institute forums - a place where a number of advocates and activists for healthy life extension gather to swap notes and plan next steps - are planning a regular voice chat event. The first will be held on March 1st to establish the level of interest and iron out the bugs:

Ok, so at night during the week seems like the best time. I am going to go ahead and make it for Thursday, March 1st at 10 pm (22:00) EST (in the US: 9 Central, 8 Mountain, 7 Western). It should last about 30 minutes to an hour, give or take a little.

Here is the calculation for the time it will be in different parts of the world at 10pm (22:00) EST March 1st:
http://www.timeanddate.com/worldclock/fixedtime.html?month=3&day=1&year=2007&hour=22&min=0&sec=0&p1=25

...

It will be a Skypecast (info on Skypecasts below), and here is the page for it (I scheduled it):
https://skypecasts.skype.com/skypecasts/skypecast/detailed.html?id_talk=470647

Hopefully it is a success!

You might want to take a brief look at the way in which Skypecasts work before diving in:

You really have to try it to see, but basically there are 3 levels of people: 1) those with permission to speak, 2) those waiting to speak, and 3) those just listening.

When you first sign in, you are in the group that is just listening (generally the largest group), and you click the "request to talk" button at the top when you want to talk, which moves you into group 2. The moderator can allow anyone to talk, bump someone from speaking ability down to regular, or bump someone from the room completely if they are being bad.

It is really very easy, and once you are in there for about 15 seconds you will realize how it works.

Post to the discussion thread if you have suggestions on procedure, specific topics, timing going forward, or any other thoughts.

Technorati tags: life extension, skypecast

Posted by Reason at 11:30 AM
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I strongly encourage everyone interested in healthy life extension to put in at least a little time to become familiar with the underlying science and concepts - how else are you to distinguish the cranks from the forward-looking researchers and advocates, if not by educating yourself as a layman? It also pays to garner a better understanding of the way in which the scientific method - the foundation of science - works in practice; you'll be far better equipped to identify the strength of support for of a concept, as well as those trying to game the system by cherry-picking results. On this latter topic, you might want to read a couple of related posts from back in the archives:

• Cranks and the Impulse to Certainty
• Faking Scientific Results Never a Long-Term Prospect
• SENS: Just Like the Rest of Science, But Not
• Magical Thinking Abounds in the "Anti-Aging" Marketplace
• On Correlation and Causation

After you have the basics down, it can't hurt to regularly stroll through the searchable archives at PubMed, or similar resource for scientific publications. It's easy enough to skip over the densely worded material that is presently beyond you (and there will always be material that is beyond you - science has grown to the point at which very technical discussions in any given field are beyond casual reading even for other scientists), and you'll usually find something interesting and new. Don't be intimidated by new words, long words and unfamiliar names; that's what Google and Wikipedia are for - make use of these resources, and benefit by them. You'll find that a good deal of scientific nomenclature is simply a matter of precision in naming, and mostly easy and helpful once you get into the swing of things. The process of learning about present research - the sort of thing you won't find in a textbook - is one of identifying common threads, and finding the links that transform what you read into a coherent whole.

Running a quick search in PubMed for "aging" today, and ordering by date, I fished out up the following items of interest from recent publications:

Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle

It is well established that neurogenesis in the dentate gyrus slows with aging, but it is unclear whether this change is due to slowing of the cell cycle, as occurs during development, or to loss of precursor cells. ... Taken together, these findings indicate that precursor cells [are] lost from throughout the dentate gyrus in old age with no concomitant change in the cell cycle time.

This first paper is interesting because it contributes to an ongoing debate I have had my eye on for some months: researchers know that stem cell activity and accompanying regenerative capabilities diminish with age. The logical explanation is that this is an evolutionary adaptation to reduce the risk of cancer due to the activity of age-damaged cells. But is there less activity due to a decline in the number of stem cells, or because the stem cells are performing less work due to environmental cues or changes in regulatory mechanisms? The strategies for restoring function - assuming you have a way to deal with the cancer risk to hand - would be different in either case, and the papers demonstrating evidence for both sides of the debate are piling up.

Molecular signaling and genetic pathways of senescence: Its role in tumorigenesis and aging

In response to progressive telomere shortening in successive cell divisions, normal somatic cells enter senescence, during which they cease to proliferate irreversibly and undergo dramatic changes in gene expression. Senescence can also be activated by various types of stressful stimuli, including aberrant oncogenic signaling, oxidative stress, and DNA damage. Because of the limited proliferative capacity imposed by senescence, as well as the ability of senescent cells to influence neighboring non-senescent cells, senescence has been proposed to play an important role in tumorigenesis and to contribute to aging.

WRN at telomeres: implications for aging and cancer

Werner Syndrome (WS) is a premature aging syndrome characterized by early onset of age-related pathologies and cancer. Since WS is due to a single gene defect, it has attracted much interest from researchers seeking to understand pathways that contribute to cancer and aging at cellular and molecular levels. The protein mutated in WS, WRN, appears to play a major role in genome stability, particularly during DNA replication and telomere metabolism. Much of the pathophysiology associated with WS, including the rapid onset of cellular senescence, early cancer onset and premature aging, can be attributed to a defect in telomere maintenance.

Telomeres - the protective ends of chromosomes that are worn away with progressive cell division - and cellular senescence play an important part in the developing picture of aging. Telomeres, and the various biochemical mechanisms for shortening and lengthening them, are the lynchpin connecting aging and cancer, part of an evolutionary balance between too little cellular regeneration and too great a risk of developing cancer. Werner syndrome is one window allowing scientists to learn more about this system as a whole - and how to manipulate it. A number of research groups are presently working on the control of telomeres with the goal of treating age-related disease or intervening in aging - it remains to be seen just where this path will go.

Microglia derived from aging mice exhibit an altered inflammatory profile

Microglia play a critical role in neurodegenerative diseases and in the brain aging process. Yet, little is known about the functional dynamics of microglia during aging. ... Aging microglia were characterized by the presence of lipofuscin granules, decreased processes complexity, altered granularity, and increased mRNA expression of both pro-inflammatory (TNFalpha, IL-1beta, IL-6) and anti-inflammatory (IL-10, TGFbeta1) cytokines. ... The low but sustained production of pro-inflammatory cytokines by aging microglia may have a profound impact in the brain aging process.

Two items here: the first is the presence of lipofuscin, one of the many "junk" chemicals that build up in the body with aging; lipofuscin is demonstrated to damage a number of important processes in the day to day operation of cells. Lipofuscin is a target for some research groups, including the LysoSENS bioremediation research funded by Methuselah Foundation donors. If you could remove this buildup of junk from cells, a number of processes would improve - this would in fact be the repair of some facets of aging in the treated tissues.

The second item is inflammation: we know that chronic inflammation over years and decades is a cause of accumulating damage in the body. This is why too much fat is a bad thing - it pumps out the cytokines too. You might find some of the information online on "inflammaging" interesting; the puzzle of the aging immune response is that it does too little and too much at the same time. It runs rampant with damaging inflammatory signaling, and yet accomplishes little of its job.

These last two papers relate to another topic of interest that I have been watching in recent months: the effect of antioxidants in cellular mitochondria on healthy life span. Antioxidants applied liberally to our biochemistry (such as those taken as supplements) appear to have little or no benefit. More advanced methologies of localizing antioxidants to the mitochondria have been shown to increase life span in mice by 20-30% or so - but this is a good deal more of an engineering proposition than a matter of ingesting the right chemicals.

Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats

The disintegration of mitochondrial membrane integrity was determined higher in the liver of old rats than that of young rats. This was well correlated with the decrease of total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase activities in most of the organs, except for the increase of catalase activity in heart of old rats. Similarly, the protein expressions of these enzymes were down regulated in the liver and kidney of old rats. Taken together, we suggest that the mitochondrial malfunction in old rats is associated with the decrease of antioxidative enzyme efficiency.

Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase

Mitochondrial superoxide dismutase (SOD-2 or Mn-SOD) is a key antioxidant enzyme that scavenges superoxide. Thus, SOD-2 may not only prevent aging-related oxidative stress, but may also regulate redox signaling in young animals. We used transgenic mice overexpressing SOD-2 to study the role of mitochondrial superoxide in aging, synaptic plasticity, and memory-associated behavior. We found that overexpression of SOD-2 had no obvious effect on synaptic plasticity and memory formation in young mice, and could not rescue the age-related impairments in either synaptic plasticity or memory in old mice. However, SOD-2 overexpression did decrease mitochondrial superoxide in hippocampal neurons, and extended the lifespan of the mice. These findings increase our knowledge of the role of mitochondrial superoxide in physiological and pathological processes in the brain.

Why the benefit from more antioxidants in the mitochondria? Well, mitochondria are damaged by free radicals such as superoxide, and this leads to a range of age-related damage and resulting degeneration throughout the body via an interesting process of many steps. But the normal operations of mitochondria (energy generation for the cell) are the source of the vast majority of these damaging free radicals - in other words, if you want to reduce the damage to mitochondria by soaking up those free radicals, you'd better put the antioxidants right at the source. Anywhere else just won't do the job.

I hope that this provides something of an illustration of the way in which you can look into aging research yourself, and learn something of what the research community is presently working on. Knowledge is power.

Technorati tags: aging, medical research, science

Posted by Reason at 1:45 PM
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Way down at the bottom of the left navigation bar of the Alcor website stands a link entitled "Epilogue." I don't know whether you folk have ever wandered that way, but it's a potent thought for the day:

What kind of world will another century bring? History teaches that humans will become much better at meeting both their basic needs and higher aspirations. People may reach across frontiers of time and space more vast than their ancestors dared dream.

The first generation that will see the 22nd century is already here. They are our young children. Among them are individuals who may see the 23rd century and beyond; people who will one day walk under strange stars and skies; people whose lives and worlds will grow beyond the imagination of science fiction.

The last generation to fall short of future centuries might not have to. All revolutions begin with a small group and a new idea. At Alcor we have an idea that may be more revolutionary than any ever before it. That idea is:

If humanity can survive long-term, then so can we.

This is why we support healthy life extension and cryopreservation research and development - because a golden future of growth and exploration lies ahead, science fiction made science fact, and to miss out on a moment of it would be a tragedy.

Technorati tags: life extension

Posted by Reason at 9:21 PM
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Scientists the world over are working hard to control stem cells - because if you can control stem cells, if you understand the biochemical cues and pathways in charge of their biomolecular machinery, you can regrow and regenerate pretty much any portion of the body you care to, as well as potentially turn off all cancers ... and those are just two of many uses for such a capability. Here are a couple of recent items from the popular science press illustrative of present work:

Liposuctioned fat stem cells to repair bodies:

Expanding waistlines, unsightly bulges: people will gladly remove excess body fat to improve their looks. But unwanted fat also contains stem cells with the potential to repair defects and heal injuries in the body. A team led by Philippe Collas at the University of Oslo in Norway has identified certain chemical marks that allow him to predict which, among the hundreds of millions of stem cells in liposuctioned fat, are best at regenerating tissue.

...

That fat-based methods work is not surprising, perhaps, because adipose tissue is closely related to bone, cartilage, muscle and other connective tissue. But some say it is impossible to re-programme adult cells to become nerve or liver cells, for example, without using embryos. Adult stem cells, such as those from fat, are thought to have more limited potential.

Collas insists that the transformation is possible. The hurdle lies not with the genes but with a cell’s epigenetic status, the subtle chemical modifications of DNA and its surrounding histone proteins. Epigenetic marks contribute to switching genes on and off, and stem cells rely on them heavily as they divide and mature. The Oslo team has found that low rates of DNA methylation, for instance, boost the chances of transforming fat stem cells from one cell type into another. "Look at a cell’s epigenetic profile," says Collas, "and you may be able to predict what that cell is likely to turn into."

How stem cells are regulated:

Director of BRIC, Professor Kristian Helin led the research team consisting of Jesper Christensen, Karl Agger and Paul Cloos. Last year, the same research group published an article in Nature on how a group of Jumonji proteins regulate the growth of cancer cells and are involved in the development of specific cancer types.

BRIC’s new results show that a different subgroup of Jumonji proteins is essential for cellular differentiation. The Jumonji enzymes can turn off, or inactivate, particular genes that play an important part in embryogenesis. The conclusions are based on studies of the nematode (roundworm) C. elegans and studies of mouse embryonic stem cells. The C. elegans studies were carried out in collaboration with another of BRIC’s research groups, led by Associate Professor Lisa Salcini.

The BRIC researchers are currently developing inhibitors to the Jumonji proteins. Their aim is to use these inhibitors to treat cancer patients with increased levels of the Jumonji proteins.

Scientists produce neurons from human skin:

Tests conducted by the researchers demonstrated that stem cells from the skin can proliferate and differentiate in vitro when placed in the appropriate environment. They progressively took on the oblong shape typical of neurons. At the biochemical level, researchers discovered that in the days following the start of the experiment, the cells began producing markers and molecules associated with the transmission of nerve impulse between neurons. "This suggests the beginning of synapse formation between neurons," points out Professor Berthod.

In the short term, this breakthrough might have an impact in the field of neuroscience research. "Producing neurons from skin cells could solve the problem of human neural cell availability for research," explains Berthod. "Since neurons do not multiply, researchers now have to rely on laboratory animal neurons to perform their experiments."

In the longer term, the ability to produce neurons from skin cells opens the door to revolutionary therapeutic applications. "We could take a patient’s skin cells and use them to produce perfectly compatible neurons, thus eliminating the risk of rejection. We could then transplant these nerve cells in the diseased areas of the brain," explains Berthod. "This type of procedure seems particularly interesting for diseases such as Parkinson’s, but it’s all theoretical for now. Before we can think of doing such things, we’ll have to improve nerve cell differentiation and prove that they can transmit nerve impulses," concludes the researcher.

Take a few minutes one of these days to stroll back a few years in the archives of one of the popular science websites - you'll be impressed at how fast the basic science is moving in this field.

Technorati tags: stem cell research

Posted by Reason at 9:46 PM
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Buried in the midst of a collections of guesses on the defining dualities of the century ahead, we have this:

Life extension for all vs for some

There will be an increasingly agonised division between those who feel that new life-extension technologies should be either available to those who can afford them or available to everyone. Life itself will be the resource over which wars will be fought: the “have nots” will feel that there is a fundamental injustice in the possibility for some people to enjoy conspicuously longer and healthier lives because they happen to be richer.

This is a sadly common viewpoint, driven by a worldview that precludes opportunity and change - not a world in which the "have nots" are beset with opportunity to become wealthier with hard work and savings, as is still the case out here in most parts of reality, despite great efforts on the part of politicians and government employees to cut the lowest rungs from the ladder.

But economic understanding aside, just how sensible is it to predict war over early healthy life extension - even when the technologies are still expensive and poorly available, before the engines of commerce and competition take over and do what they do for every new technology; bring down the price, make the goods better, and increase the level of safety? Even in this over-regulated medical socialism in the Western democracies, was there a war over heart surgery? Only the rich could get their hands on that back in the day, and that made a big difference. Is there a war right now over the rationing of Alzheimer's treatments in the UK, treatments that any wealthy individual can obtain on their own dime? Is there a war brewing over stem cell therapies for heart disease, again something unavailable as yet to those of us who have not saved up enough for a down-payment on a nice house?

At least in the case of these two technologies for the heart, competition and research is steadily driving down costs and improving quality, despite the choking regulatory burden that makes research and development far more costly and slow than it might be. But in the case of the UK rationing, the heavy hand of government is the problem, and things are unlikely to become better until that changes.

The world is unfair to those who choose to be poor, and far more unfair to those whose escape from poverty is closed off by corrupt and malign governance. This is a simple truth: if you have less, you can buy less, and that includes the use of medical technology to improve health and lengthen healthy life. Yet most people have the opportunity to escape from poverty on timescales far shorter than their life span. A world of both dramatic inequality and opportunity for all is a far better world than one of utter equality and absent opportunity - because you cannot build the latter world without tearing down every engine of progress and reducing society and its works to a wasteland. It is the opportunity to climb that ladder - and the freedom to undertake that work - that drives human ingenuity, competition and the provision of ever better goods and services at all levels.

There will be no war so long as there is freedom, opportunity and the prospect for ongoing improvement at every level. It is where these opportunities and avenues of progress are blocked that conflict occurs.

Technorati tags: libertarian, life extension

Posted by Reason at 9:13 PM
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Following up on my last post on cancer research, I thought I'd point out a release illustrative of the search for keys to cancer - and the ongoing process of evaluating whether it is even sensible to be searching for such keys. By "keys" I again mean some sort of common mechanism, or small number of common mechanisms, by which all (or even almost all) cancer could be prevented or successfully treated with the technology of the next decade - if only we knew these keys existed.

Most types of cancer are believed to begin with a random genetic mutation that makes a normal cell go horribly awry. This is followed by mutations, which endow the cancer cells with properties allowing them to grow without normal controls to become a tumor. These mutated genes would be targets for chemotherapy.

But Loeb had another idea that he originally hatched many years ago – what if the cancer cells changed somehow, and became much more likely to mutate? These "mutator" cells would develop dangerous genetic mutations at a much faster rate than normal cells, which might account for the high number of mutations seen in tumor cells.

Since the technology of cancer genetics has dramatically improved, Loeb and his colleagues have only recently been able to test this hypothesis. They found that tumor tissue had random mutation rates up to 100 times higher than normal tissue from the same patient. The "mutator" hypothesis seems to be correct.

Now for the bad news: if cancer cells do indeed become "mutator" cells, traditional chemotherapy and other drugs may never be very effective against advanced tumors.

...

Loeb’s work may also lead to a discovery of why cancer cells are becoming mutator cells. If scientists understand what happens in a cancer cell that makes it become a mutator, they might be able to prevent that from happening in other cells, or slow down the mutation rate.

"The idea is that if you might normally get exposed to something in the environment at 20 years old that would give you cancer by age 55, then if we cut the mutation rate in half, you might not get cancer until age 90, and you may even die of something else before that," Loeb explained.

You might recall a similar look at a potential root cause leading to greatly increased rates of mutation was mentioned a little while back at the Longevity Meme:

When the teams compared patterns of gene activity in stem cells from healthy and cancerous tissue they found that those from cancers were often locked in a state in which they carry on multiplying as primitive stem cells, instead of maturing into specific tissues. ... When they're in this state they divide more, and in the process may accumulate additional mutations which ultimately turn them cancerous.

What are the real roots of cancer? Do the keys to cancer exist in a form that we can find and take advantage of within the next decade or two? Can researchers produce global anti-cancer technologies dramatically better than the development of an effective therapy, one type of cancer at a time? Stay tuned.

Technorati tags: cancer research

Posted by Reason at 9:32 PM
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Biochemists and a range of other scientists devote a great deal of time and resources to understanding and manipulating the processes of oxidation in the body - free radical generation, discovery, design and manufacture of antioxidants, oxidative stress, impact of reactive oxygen species on age-related conditions and physiological changes, and so on. This is to good ultimate end; a couple of new animal studies in recent years have demonstrated extended healthy life spans as a result of careful direction of antioxidants, for example. All too often, however, the scientific story is "works in the test tube, no effect in living animals." No shame in this - any story of progress is that of a series of inventive failures preceding ultimate success.

Since the early 1990s scientists have been putting these compounds through their paces, using double-blind randomised controlled trials - the gold standard for medical intervention studies. Time and again, however, the supplements failed to pass the test. True, they knock the wind out of free radicals in a test tube. But once inside the human body, they seem strangely powerless. Not only are they bad at preventing oxidative damage, they can even make things worse. Many scientists are now concluding that, at best, they are a waste of time and money. At worst they could be harmful.

There are good reasons for this general failure of antioxidants applied as supplements after promising test results on cells; the full complexities of a living being are a far cry from a modest selection of cells in a petri dish. The recent antioxidant research initiatives that do extend life in animals are an entirely more ambitious endeavor than the work of past generations - clever biochemistry, gene therapy, mitochondrial targeting, and a far greater knowledge of the internal workings of the cell.

None of this stops folk within "anti-aging" marketplace making money on antioxidant supplements shown to have no effect in animal studies; nor should it, for that matter. Caveat emptor is a good rule, alongside a free market in reviewing organizations - a much better rule than centralized regulation. Do the small amount of research yourself to find out who is talking nonsense; it's not hard. You do it when you buy a new car, or a new computer, so why not with something you plan on ingesting for the next few decades or so? All industries are just as packed with people who can pass for legitimate, talking the talk, but who are in actual fact full of it and on the take. Learning to tell who is who is part and parcel of living a good life, and is a responsibility you should take especially seriously when it comes to your health.

You'll see a certain dynamic tension at the intersection of the scientific and "anti-aging" communities around antioxidant research - the scientific rejects, those shown to have no effect in animal studies, still make people money on the back of promising, selectively presented early test tube results. It makes it very clear that the "anti-aging" marketplace is a mature delivery system that came into being prior to any actual, real anti-aging medical technology. Lack of a real product has never been any barrier to misapplied human ingenuity and the burning need for answers now, this very instant, however.

A representative article showed up in an Australian daily recently:

The product, gamma glutamyl cysteine (GGC), is a precursor of a so-called master anti-oxidant naturally produced by our bodies.

That compound, glutathione, helps protect us against the damaging effects of free radicals ... As people age, their cells' components become oxidised, and this leads to age-related diseases. What we're hoping to do is re-build glutathione in the cells to a normal, healthy level,

...

Dr Bridge and his colleague Dr Martin Zarka have invented what they say is a low-cost process for producing this natural compound so it can eventually be added to foods, vitamin pills, toothpaste or cosmetics.

One of the first practical applications, currently being developed, is a skin-repair cream.

Dr Bridge says the next phase of experimentation is to confirm whether GGC can increase the glutathione content of cells grown in laboratory conditions.

...

As we grow older, our glutathione levels drop, and our ability to detoxify free radicals decreases.

Unfortunately, increasing glutathione in our diet won't solve the problem. Many foods, such as yeast extracts, are rich in glutathione but the glutathione can't directly enter the body's cells where it's needed.

So, yes, same old, same old. On the one hand, the ultimate goal of the science is sensible: identify a way in which our biochemistry changes with age and look for a way to fix it. Not to mention that any future use for glutathione will benefit from the better manufacturing process devised by these researchers. On the other hand ... skin cream based upon tests on cells in the lab - it's not as though we haven't seen that a hundred times before to no good end; tests worth making even with low expectations in the best case, modern magical thinking in the worse cases.

We're a smart species. We can do better than this.

Technorati tags: anti-aging, science

Posted by Reason at 3:31 PM
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The cancer research establishment seeks - as a near-term goal - to develop the means to turn almost all cancers into managed conditions. Possibly costly and inconvenient, but not fatal, just as researchers have accomplished for class after class of medical conditions over the past century - and they were hard tasks all. As suggested by a recent Technology Review piece, however, we might ask ourselves what sort of hard task this is in the case of cancer - easy hard or hard hard:

The largest study yet of genetic changes across a broad range of cancers has turned up some unexpected results. Mutations thought to cause one kind of cancer also seem to be important in others, suggesting that the same drugs might be useful for patients with very different kinds of cancer. But all the mutations in the study--even those shared among cancers--occurred at low frequencies, suggesting that the search for cancer genes may be more difficult than researchers had hoped.

...

But Chanock says the study also provides "a good reality check." Thirty percent of the tumors in the study had none of the mutations Garraway's group looked for. Chanock says this study forces researchers to address the question, "What's it going to take to make sense of [the genetic changes behind cancer]?" The answer, he says, is even larger genotyping studies, on the order of 10,000 tumors. And, as those tumors with no known mutations in this study suggest, many of the genetic changes that drive cancer remain to be discovered.

Genes are keys to cancer, because they are a starting point from which to