Longevity Meme Newsletter, March 01 2010

March 01 2010

The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.



- Reversing Blindness With Stem Cells
- A Few Articles on Cancer Stem Cells
- Regulatory Incentives in Research
- Discussion
- Latest Healthy Life Extension Headlines


Researchers have been working to generate new retinal cells for some years now; it's one of the longer running initiatives in regenerative medicine. A reliable source of replacement retinal cells could be used to restore sight to those suffering from age-related macular degeneration, the genetic condition of retinitis pigmentosa, and some other forms of blindness. Some years after first generating retinal cells from stem cells, scientists have now reached the milestone of restoring sight in mice:


"An international research team led by Columbia University Medical Center successfully used mouse embryonic stem cells to replace diseased retinal cells and restore sight in a mouse model of retinitis pigmentosa. ... In Dr. Tsang's study, sight was restored in one-fourth of the mice that received the stem cells. However, complications of benign tumors and retinal detachments were seen in some of the mice, so Dr. Tsang and colleagues will optimize techniques to decrease the incidence of these complications in human embryonic stem cells before testing in human patients can begin. 'Once the complication issues are addressed, we believe this technique could become a new therapeutic approach for not only retinitis pigmentosa, but age-related macular degeneration, Stargardt disease, and other forms of retinal disease that also feature loss of retinal cells,' said Dr. Tsang."

Partial success and complications are fairly typical for first efforts. The recent past of biotechnology development shows us that rapid improvement is to be expected once the first promising results are attained.


The application of knowledge gained from the field of regenerative medicine to cancer research is one of the more exciting areas of modern life science. A robust cure for cancer is, of course, a required line item if we are to fully benefit from other forms of longevity-enhancing medicine:


"Cancer stem cell theories offers the prospect that various types of cancer spawn from characteristic stem-cell-like initial populations. Cancer exists because random mutations that occur in our cells as a result of damage and age will eventually produce one of these prolific and damaging cell types, possibly by damaging an existing adult stem cell, or possibly by radically mutating a normal somatic cell. Cancer stem cells are hard to eradicate completely through old-style chemotherapy, radiotherapy, or surgery, which is why cancers tend to recur - all it takes is one remaining errant stem cell to rebuild the cancer anew. But the nature of cancer stem cells also means that they are the weak link: destroy them and the cancer cannot survive. Fortunately, identifying and safely destroying specific cell types based on their biochemical differences is a core focus for biotechnology research these days. This is one of the reasons I am confident that my generation will not suffer greatly from cancer in later life: the cancer-killing therapies of three decades from now will be very safe, very effective, and very cheap."


Rapamycin is an immune-suppressant drug that is presently in use and approved by the FDA. It was also recently shown to extend healthy life in mice - which means a great deal of attention is now focused upon finding evidence that might show rapamycin can be used to slow progression of degenerative conditions of aging. Unfortunately, this has a lot more to do with its approved status than with the objective merits of the science, I suspect:


"I'm of the opinion that the existence of the FDA creates a 'looking for the keys under the lamppost' syndrome amongst researchers. The results we actually want - reversal of aging, bold new discoveries in biotechnology, and so forth - lie somewhere out there in the darkness, beyond what has been FDA approved, and in most cases beyond any framework the FDA has set in place to consider medical technologies. But how much easier it is to stick to the small circle of light and commercialize new uses for an already approved drug! The FDA's oppressive regulatory costs create a perverse incentive for researchers to focus their resources upon reuse of existing drugs, work that will never produce anywhere near the benefits that might be realized from completely new developments in medical technology. So we all suffer, and we cannot see the true cost, because that cost is measured in technologies and medicines that might have been brought into being by now, if not for the regulators."


The highlights and headlines from the past week follow below.

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Intriguing research: microvesicles "are several times smaller than a normal cell and contain genetic information such as messenger ribonucleic acid (RNA), other species of RNA and protein. ... During times of cellular injury or stress, or with certain diseases like cancer, infections and cardiovascular disease, these particles are shed and then taken up by other cells in the body. The genetic information and protein in the microvesicles helps to reprogram the accepting cell to behave more like the cell from which the particle was derived. ... Our work suggests that when the lung is injured or diseased and cells within the lung are stressed or dying, they shed microvesicles. Those microvesicles are then consumed by cells within the bone marrow, including stem cells, which are present in small numbers within the circulatory system. Those bone marrow cells then turn into lung cells. ... microvesicles not only supply information to stem cells with lung injury, but this process also occurs in other organs as well, like the heart, liver and brain. ... the change in those stem cells that have consumed microvesicles made by injured lung cells is very stable - the change appears to be permanent. ... This would be relevant to any type of disease - if you want to repair damaged tissue, these microvesicles potentially provide a durable fix, and the hope is that it would be fixed forever."

From the Campaign Against Aging website: "Pictures have just been uploaded of Doug distributing flyers to students at a college campus. ... I had a great time distributing these flyers. I would say 70% or more of the reactions I got were positive. Under 10% of people did not take a flyer, and about 20% responded negatively. I used a few different slogans while distributing the flyers. For the most past I used 'Death sucks. We should stop it.', followed by 'Dying is bad. We shouldn't do it.', and least frequently 'Getting old sucks. We should do something about it.' I got the highest proportion of positive reactions in the same order (which is why I used 'death sucks' most frequently). I distributed about 200-300 flyers total today. ... I talked to several people and groups at length about what is involved in fighting aging. I explained that aging is not a magical process and that we do not have a clock inside our body that makes us get older. Aging is just a building up of damage over time inside our cells, and that damage can be reversed. I explained briefly a few of the different kinds of age related damage, including lipofuscin accumulation and protein cross linking."

Chinese researchers here demonstrate that some forms of fetal stem cell transplant are unambiguously beneficial in mice - the absence of cancerous development is perhaps surprising. This suggests that if an individual's stem cells could be sampled, altered to look more like fetal stem cells, and returned to the body, then they could achieve the same end: a general improvement in tissue repair, bodily systems, and life expectancy. From the paper: "To determine the role of allogeneil graft of mesenchymal stem cells in mammalian longevity, mesenchymal stem cells were isolated from [mouse fetal tissue] and then were purified and amplified by adherent culture. Identified P1 mesenchymal stem cells were injected [into] the 15-month-old [mother mice] three times. The mice were evaluated ... The results showed that after transplantation, the long-term surviving stem cells were found to be located in many organ tissues ... Median life span was increased in these animals after transplantation. Skin, cardiac, lung, kidney and colon pathology development were delayed. [Amongst other markers of aging, the degeneration] of heart function was attenuated [and markers of oxidative stress] were reduced three months after transplantation. These results support the idea that longevity can be enhanced by transplantation of mesenchymal stem cells."

Via CryoNet, some advice to follow on from the cautionary tale of a few days ago: "There has been some discussion about relatives causing suspensions to not take place as the cryonics member gets older and how we cryonicists can protect ourselves from this happening. Suspension interference happens more then most cryonicists realize. As a retired member of of Alcor management I have seen a lot of it. ... You think your relatives will continue to honor your wishes as you grow old? A lot of them will tall you to your face that they will, but in reality they believe that cryonics is a waste of your time and your money. So they have no moral reservations about causing you to cancel your membership and have the money go to them if and when they get a chance to take over. How can you protect yourself? Make sure that your life insurance policy says that if you don't get suspended for any reason that the proceeds still go to your cryonics organization and not your relatives. So there is no financial incentive for the relatives to cause you to cancel your arrangements. Put a clause in your will that says that if you don't get suspended that all your estate goes to your cryonics company and not your relatives so that there is a financial incentive for your relatives to see that you do get suspended."

Given the vast weight of evidence, it would seem straightforward to say that regular exercise is good for health and longevity. But of course, nothing is ever as simple as we'd like in biology: "We know that exercise is good for us, and increasingly we're understanding how it works at the molecular and cellular level: Physical activity boosts levels of heat shock proteins, which help cells resist stress; it also improves mitochondrial function in a manner reminiscent of calorie restriction (CR). Our knowledge is sophisticated enough that we can identify and develop small-molecule exercise mimetics and drugs that improve exercise tolerance. Overall, then, exercise and its molecular/cellular consequences are consistent with longevity assurance pathways and life extension interventions. However, there are complications emerging. ... In blood flow restriction (BFR) exercise, resistance training is combined with pressure cuffs that significantly decrease blood flow to the exercising muscle; it increases protein synthesis in muscle cells and activates the TOR pathway. Now, Fry et al. have shown that in older men (who don't increase muscle mass in response to ordinary resistance training), BFR activates TOR. Superficially, this would seem to represent a contradiction: a lifespan-extending intervention (exercise) activates a lifespan-shortening biochemical signaling pathway (TOR). How might this seeming paradox be resolved?"

From the Technological Citizen: "are Kurzweil's visions of immortality even close to being feasible, given the current state and direction of today's technological advancements? When it comes, realistically, to life extension technologies, where do we really stand today? There's perhaps no group of people to better answer this question than the people of Methuselah Foundation, a non-profit organization founded by David Gobel, which supports Aubrey De Grey's SENS research and is dedicated to enabling humans 'to live longer, better and wiser, by defeating age-related disease and suffering.' I had the privilege of speaking to Roger Holzberg, the Chief Marketing Officer and Creative Director of Methuselah Foundation, about the core philosophies of the foundation and the promising research they are involved with. I asked Mr. Holzberg, what are the areas of life extension available now, and in our short-term future? What fundamentally drives the foundation towards seeking these life extension solutions? ... treating aging as a 'disease' and not a given in life is one of the principle philosophies of Methuselah Foundation. Towards this end, the foundation takes a very methodical, systematic approach to life extension, working to prevent and manage the diseases of aging such as cancer, heart disease, and diabetes, and to encourage research into new ways of prolonging life."

AN INTRODUCTION TO FOXO3A (February 23 2010)
Singularity Hub provides a popular science introduction to the FOXO3A gene and its role in human longevity: "The past few decades have seen a growing interest in longevity as medicine continues to advance life expectancy. Groups like the Methuselah Foundation (sponsors of the MPrize) are actively seeking technology to extend lifespans. Yet, understanding aging is not an exact science. We do know that genetics, environmental risks/lifestyle, and strong social bonds are all part of what helps someone live longer. Studies of centenarians, however, have suggested that while genetics don’t seem to make a big difference in the early decades of old age, they have a profound effect determining who makes it into extreme old age. Variants in FOXO3A may be one of the key ingredients that help take a healthy 80 year old, and turn her into a healthy 110 year old. ... everyone has a FOXO3A gene. It is the variation in single sections of that gene (single nucleotide polymorphisms) which are important. ... As we better understand which of these SNPs are key for longevity, you'll be able to test for them with personal DNA tests or whole genome sequencing. ... The FOXO3A gene codes for the FOXO3A protein. If we figure out how longevity variants of FOXO3A change the protein (in its form, frequency, etc) we could then produce drugs that replicate that change and give our bodies long life."

A CAUTIONARY TALE (February 23 2010)
The two greatest practical hurdles to cryonics are organizational in nature, not technology problems. Firstly to overcome inertia and do the work necessary to sign up as a member of one of the cryonics providers, and secondly to evade all the potential issues and problems that might occur at the time of suspension. This is particularly challenging if death comes unexpectedly, but the cautionary tale I link to here illustrates another common problem. What if your relatives decide to overrule your wishes once you are no longer capable of enforcing your original decision? "In 2006, [Mary Robbins] signed documents giving the Alcor Life Extension Foundation of Scottsdale, Ariz., the right to cryogenically preserve her head and brain. She also agreed to give the nonprofit foundation a $50,000 annuity to cover preservation costs. Her daughter, Darlene Robbins, said her mother changed her mind in her last days because of the procedures that preservation would have required before she died, including tubes in her throat and nose, intravenous lines and medications. Mary Robbins signed new paperwork that would give her family the annuity, the daughter said ... Eric Bentley, an attorney for Alcor, said Mary Robbins didn't sign a written notice rescinding the 2006 agreement. He said Alcor wants to honor the wishes she expressed in that document." From the outside, this looks a lot like the family decided that they wanted that $50,000, and to hell with Mary Robbin's desires - but we will never know for sure. Those folk signed up for cryonics should learn from these events, and adjust their own arrangements accordingly.

From the Economist: "The great hope of transplant surgeons is that they will, one day, be able to order replacement body parts on demand. At the moment, a patient may wait months, sometimes years, for an organ from a suitable donor. During that time his condition may worsen. He may even die. The ability to make organs as they are needed would not only relieve suffering but also save lives. And that possibility may be closer with the arrival of the first commercial 3D bio-printer for manufacturing human tissue and organs. The new machine, which costs around $200,000, has been developed by Organovo, a company in San Diego that specialises in regenerative medicine, and Invetech, an engineering and automation firm in Melbourne, Australia. ... The first production models will soon be delivered to research groups which [are] studying ways to produce tissue and organs for repair and replacement. At present much of this work is done by hand or by adapting existing instruments and devices. To start with, only simple tissues, such as skin, muscle and short stretches of blood vessels, will be made [and] these will be for research purposes. ... the company expects that within five years, once clinical trials are complete, the printers will produce blood vessels for use as grafts in bypass surgery. With more research it should be possible to produce bigger, more complex body parts. Because the machines have the ability to make branched tubes, the technology could, for example, be used to create the networks of blood vessels needed to sustain larger printed organs, like kidneys, livers and hearts."

SOIL FOR SENS (February 22 2010)
From the Immortality Institute: "Five years ago began one of the most interesting collaborative research projects in the anti-aging field. The concept was bioremediation of indigestible metabolic byproducts in order to improve the health and functioning of human cells. It is well known that these byproducts are prevalent in cases of Alzheimer's (amyloid beta and tau proteins) and heart disease (7 ketocholesterol) among many other age-related diseases. For whatever evolutionary reason, the human body does not produce enzymes to break down this 'junk'. Aubrey de Grey of the SENS Foundation theorized that out in the wilds of nature there must be some bacteria that break down this junk. ... The SENS Foundation put out a call around the world for interested longevity-minded people to send in soil samples. Immortality Institute members responded, enthusiastically sending in hundreds of samples from gardens, forests, deserts, and swamps. The tale of cooperation and outreach is preserved in this Imminst forum. The research was also the subject of an Imminst Sunday Evening Chat in 2007. ... Since the call went out, researcher John Schloendorn and several other Immortality Institute members [have] been testing the soil samples for bacterial enzymes that could break down the plaques and other junk. A multitude of bacteria were tested on the various types of cellular and extra-cellular junk to see which ones would thrive. Several bacteria were up to the job."



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