Longevity Meme Newsletter, June 02 2008

June 02 2008

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.



- Recent Directions in Alzheimer's Research
- Looking Far, Far Ahead
- The Ball and Chain
- Discussion
- Latest Healthy Life Extension Headlines


As you might know, much of Alzheimer's research has been - and still is - focused on the removal of amyloid plaques in the brain. Over the past five years, as the capabilities of biotechnology have grown, a number of interesting new directions have emerged:


"There's the choroid plexus connection, and the possibility of repairing the normal mechanisms of amyloid removal, for one. It turns out that amyloid creation and removal are actually very rapid, dynamic processes, and the buildup towards Alzheimer's is a slowly growing imbalance between ongoing creation and removal. Also, the realization that Alzheimer's looks an awful lot like type 2 diabetes at a biochemical level, with all the same lifestyle risk factors relating to exercise, eating and visceral fat. Lastly for this list, there is some form of biochemical connection between Alzheimer's and the inflammatory immune response."

Researchers have demonstrated 90% removal of amyloid plaque in mice through experiments with the immune response, and a corresponding improvement in the brain health of those mice. Just as for promising initiatives aimed at the repair of type 2 diabetes in recent years, this is good news - but don't forget that Alzheimer's, like type 2 diabetes, appears to be a lifestyle disease. It may be avoidable for most people.

If you want to ensure the best chance of suffering both type 2 diabetes and Alzheimer's disease, then stop exercising, eat a terrible high-calorie diet, and pack on the weight so as to gain that damaging visceral fat and the chronic inflammation it causes:



"First things first" is a good philosophy to live by, but it doesn't hurt to spend a little time thinking about what comes after the first step. Here, the first step is the comprehensive repair of aging through medical science, and rejuvenation of the old - a very big first step, but we know more than enough to get underway. If you're new to that concept, you might want to look at the Strategies for Engineered Negligible Senescence:


When step one is done, what, then, is your step two? You'll have a great deal of time to work on it. Personally, I'm up for pushing the boundaries of an enjoyable life out even further:


"I'm not going to try to convince you that the future will be a golden, wondrous place: either you accept the implications of the present rate of progress towards what the laws of physics make possible, in which case you've probably thought this all through at some point, or you don't. Life, space travel, AI, the building blocks of matter: we'll have made large inroads into bending it all to our will within another half century. Many of us will live to see it even without the benefits of medical technology to come: growing up in a 1970s urban area will be the new version of 1900s farmboy youth come 2040; a strange and primitive near-past erased by progress, for all that so many people still alive actually lived it, time travelers in their own lifetimes.

"If you project out the accident rates for life today, you'll see that an ageless human, sustained by foreseeable biotechnologies of cellular and biochemical repair, has a life expectancy in the 1000 to 5000 year range. Sooner or later that piano is going to fall on you hard enough that even advanced medical technology can't fix you up.

"Once you start looking at living for 100,000 years in much the same shape as you are today, it becomes apparent that almost any activity bears a level of risk that'll jump up and kill you. Eating, swimming, reading ... breathing. Stretch out the time for long enough and the improbable and fatal will happen to you.

"The answer is to change the shape you are. Getting past step one, the repair of aging, gives you a few hundred years of comparative statistical safety. I can't imagine that much of the technology needed for step two will remain beyond the human civilization of the 2200s."

As I said, it's good to have spent a little time on speculative, realistic plans for the long term. But we can't forget that step one, the work needed to develop and commercialize the medicines of repair for aging, is by no means certain. It'll happen sooner or later, but "later" isn't so good for those of us reading this now:


We have a lot of work to do to ensure that the best scientific paths to rejuvenation are funded, and that capable research communities grow to take advantage of that funding. An amazing future is ascending to great heights ahead of us, and it would be a crime to miss out on it because we didn't lay the groundwork now.


Not everything is roses, of course, and the largest barriers to progress these days are those we build ourselves:


"No new drug for prostate cancer has been approved by the FDA in 20 years. Twenty years! Just stop a moment and think about how far and fast biotechnology and medical science has moved in the past twenty years. Think about what the far less regulated computing industry has achieved in the same timeframe. We live in the early years of the biotechnology revolution, with something amazing and new demonstrated in laboratories every week. Yet the dominant regulatory body for one of the most advanced regions of the world has managed to stop the clock at 1988 for a major disease, the subject of research in a hundred laboratories worldwide.

"This situation exists in every field of medicine, and all participants labor under the crushing burdens imposed by regulators incentivized to stop progress from happening. The same will be true of the future of longevity medicine, unless we do something about it."


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

We Have Artificial Viruses Now, Also (May 30 2008)
Researchers can build artificial cell components, and are well on the way to artificial cells, so why not artificial viruses as well? "Natural viruses are extremely effective at transporting genes into cells for gene therapy; their disadvantage is that they can initiate an immune response or cause cancer. Artificial viruses do not have these side effects, but are not especially effective because their size and shape are very difficult to control - but crucial to their effectiveness. A research team [has] now developed a new strategy that allows the artificial viruses to maintain a defined form and size. ... Glucose building blocks on the surfaces of the artificial viruses should improve binding of the artificial virus to the glucose transporters on the surfaces of the target cells. These transporters are present in nearly all mammalian cells. Tumor cells have an especially large number of these transporters. Trials with a line of human cancer cells demonstrated that the artificial viruses very effectively transport an siRNA and block the target gene. ... researchers were able to attach hydrophobic (water repellant) molecules - for demonstration purposes a dye - to the artificial viruses. The dye was transported into the nuclei of tumor cells." A nice technology demonstration, and the wave of the future in making gene therapy more effective, no doubt: we can take from the mechanisms we find in nature, and then improve on them.

Why Is Cryonics So Unpopular? (May 30 2008)
People are clearly interested in cheating death. Why, then, do they chase all sorts of magical thinking and pseudoscience rather than one of the few methods that should actually work? From Depressed Metabolism: "In his 1998 essay 'The Failure of the Cryonics Movement' (part 1, part 2), Saul Kent stresses that cryonics has remained so unpopular because nobody thinks it will work. ... The view that acceptance of cryonics is being held back by the perception that it is not technically feasible is hard to reconcile with the observation that increased technical progress in cryonics does not translate into rapid membership growth. It is also hard to reconcile with the fact that millions of people hold on to views that cannot be falsified with any scientific method whatsoever. Perhaps there is a scientific tipping point beyond which people will sign up in droves for cryonics. For example, some cryonics activists argue that demonstration of reversible vitrification of a small animal will have such an effect. This may or may not be the case, but it still leaves the puzzle unresolved as to why cryonics organizations were not swamped with membership requests after publishing electron micrographs that demonstrated excellent ultrastructural preservation of brain tissue after vitrification."

An Interview With James Thompson (May 29 2008)
Some interesting comments in this Forbes interview with stem cell researcher James Thompson: "Most of the hype about embryonic stem cells has been about replacing damaged body parts, but Thomson sees real promise in drug discovery. ... These cells suddenly give us access to all the bits of the human body we've never had access to. That's going to lead to understanding why certain cells are dying, and more traditional therapies are likely to prevent them from dying. Parkinson's, if you can diagnose somebody early in the course of that disease and arrest it, that's as good as a cure. And that I think is fairly probable. ... I'd actually be fairly shocked if 10 or 20 years from now we didn't have such a good understanding of the biology of [Parkinson's] that we didn't have to do transplantation [of new neurons]. And although human embryonic stem cells and induced pluripotent stem cells are not the whole story for doing that, I think they're going to be one critical component of it."

Exercise and Cancer (May 29 2008)
From EurekAlert!, another way in which exercise helps healthy longevity: "Men who exercise often are less likely to die from cancer than those who don't exercise ... In the study, the researchers looked at the effect of physical activity and cancer risk in 40,708 men aged between 45 and 79. Over the seven year period of the [study], 3,714 men developed cancer and 1,153 died from the disease. Men who walked or cycled for at least 30 minutes a day had an increased survival from cancer with 33 per cent, than the men who exercised less or did nothing at all. The researchers also found that a more extensive programme of walking and cycling for between 60 and 90 minutes and a day, led to a l6 per cent lower incidence of cancer. But these activities only led to a five per cent reduction in cancer rates among the men who walked or cycled for 30 minutes day, a finding which could be due to chance." One might speculate that this has to do with maintaining a more capable immune system (which can destroy cancer at the earliest stages) and losing the visceral fat, thereby reducing chronic inflammation. Less biochemical damage to the body's vital systems means a lower chance of runaway failure in your cells.

Efficiency In Engineered Pluripotency (May 28 2008)
Infrastructural improvement is key; making the tools faster, better and cheaper will speed progress. Here's another good example via EurekAlert!: "The ability to drive somatic, or fully differentiated, human cells back to a pluripotent or 'stem cell' state would overcome many of the significant scientific and social challenges to the use of embryo-derived stem cells and help realize the promise of regenerative medicine. Recent research with mouse and human cells has demonstrated that such a transformation ('reprogramming') is possible, although the current process is inefficient and, when it does work, poorly understood ... We used a genomic approach to identify key obstacles to the reprogramming process and to understand why most cells fail to reprogram ... Previous work had demonstrated that four transcription factors - proteins that mediate whether their target genes are turned on or off - could drive fully differentiated cells, such as skin or blood cells, into a stem cell-like state ... Interestingly, the response of most cells appears to be activation of normal 'fail safe' mechanisms. Improving the low efficiency of the reprogramming process will require circumventing these mechanisms without disabling them permanently."

What To Rejuvenate First? (May 28 2008)
Hypothetical choices from FuturePundit: "Suppose you find a lamp that contains a genie. Suppose the genie grants you 3 wishes to make parts of your body young again. You have to use the wishes by age 55 (before most old age diseases become apparent) or immediately if you are already over 50. The wishes are for only parts of the body. Each could make an organ (and the skin is an organ) or subsystem (e.g. immune cells or spine) young again." This is something of a proxy for the question "what specific rejuvenation research would you fund if you had a vast sum of money?" Tissue engineering for a new heart, plus the necessary understanding to repair any damage in your stem cells? One problem you quickly run into in this sort of thought experiment is that everything of importance is influenced by everything else. New cells will be damaged by the old intracellular environment, as well as by the actions of old cells next door. An age-damaged immune system can't protect rejuvenated cells in a new heart. The interconnectedness of the body's systems is one of the reasons I favor the fundamental engineering approach: get to the bottom of the biochemical damage and fix it. Take care of the cells and the environment and the organs will take care of themselves.

More On Infection and Telomere Length (May 27 2008)
Ouroboros comments on recent research indicating that infection shortens telomeres in immune cells: "Chronic stress has been associated with decreased telomere length in lymphocytes. The association is robust and has been observed in multiple studies ... The question still remains, however, whether the relationship is correlative or causative. Do stress and other lifestyle factors somehow cause shortened telomeres, or are the two phenomena otherwise-unrelated indications of some common underlying cause? ... Chronic infection requires increased production of lymphocytes, which overworks the stem cell compartment from which these cells are derived; increased cell divisions leads to decreased telomere length - a perfectly satisfactory explanation for the observation. If that is true, then chronic infection in the absence of lifestyle risk factors should cause telomere shortening on its own (let's stipulate for the moment that stress increases susceptibility to disease, an idea supported by my own anecdotal experience of college finals). Ilmonen et al. have demonstrated that this is indeed the case, at least in [mice]."

On Aging Presented as a Disease (May 27 2008)
From Existence is Wonderful, thoughts on presentation: "Nowadays, there are a lot of people (perhaps even a majority!) interested in mitigating common age-related health problems. Very few people would answer 'Yes!' if asked, 'Are you looking forward to experiencing heart problems, increased susceptibility to infections and cancer, and eventual death?' However, most people also accept certain things as inevitable or at least highly probable, and may strongly object to the characterization of the aging process as a 'disease' in and of itself. ... To some, calling aging a 'disease' implies that there is something 'wrong' with old people as they exist today, and that us younger folks all ought to feel sorry for these poor, sick individuals. I know that not everyone has this interpretation, but that interpretation does exist, and I believe it to be a rather problematic one." I don't agree with this line of reasoning - you should read the whole thing - but I do agree that there's a lot of work left to do on the presentation and perception of longevity science and the degenerations of aging.

Upgrading Cells With Intrabodies (May 26 2008)
EurekAlert! examines another technology with the potential to clean up cells of compounds that accumulate and damage us with age. Here it's aimed at Huntington's disease, but you can see the potential for broader application: "researchers engineered a virus to make an intracellular antibody or 'intrabody' against huntingtin, the protein whose mutant forms poison the brain cells of people with Huntington's. Injecting the virus into the brains of mice that make mutant huntingtin improves their ability to move their limbs ... Delivering the intrabody to brain tissues in people would be a formidable challenge, because it would require some form of gene therapy ... finding an antibody that prefers to bind mutant, aggregated protein could also prove useful in the study of other neurodegenerative disorders, such as Alzheimer's disease or Creutzfeldt-Jakob disease. ... Several neurodegenerative diseases appear to involve defects in protein folding and metabolism, leading to the accumulation of protein aggregates inside cells. Our study suggests a strategy for dissecting the harmful effects of these protein aggregates in other diseases."

Aging Is An Anti-Process (May 26 2008)
Thoughts from grailsearch.org: "In essence, aging is not a process but rather an anti process. As DNA driven life forms, we are the sum of our gene expression driven by numerous molecular dials turning protein production up and down. As time passes though, the optimal concentration of the expressed proteins within us slowly becomes unbalanced. This imbalance leads to dysfunction, disease states and exposes us to many forms of environmental, microbial, viral and even self-induced damage. The good news is that the network of gene regulation has a tremendous amount of redundancy and fault tolerance designed into it from millions of years of evolutionary pressure which allows us to live as long as we do. From a systems perspective, how long we live is quite extraordinary, however [we're] probably getting close to pushing the limits on how far this system can perform without any assistance. Even with calorie restriction, optimal nutrition, supplementation, exercise and stress management, it's unlikely that a system with so many variables cannot lose its fidelity with the passage of this much time." Assistance means biotechnologies of repair and gene network control - which could be well underway if enough people wanted it to be well underway.



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