FIGHT AGING! NEWSLETTER
March 26th 2012
The Fight Aging! 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 Fight Aging!
- SENS5 Video: Correcting Mitochondrial Mutations
- Another of the Cryonics Pioneers is Cryopreserved
- Theorizing on Evolution and Longevity
- Latest Headlines from Fight Aging!
SENS5 VIDEO: CORRECTING MITOCHONDRIAL MUTATIONS
Here is more on the new method for working around mitochondrial DNA damage that has been in the news recently:
"Mitochondria crowd your cells, roving descendants of ancient bacteria that were long ago co-opted to serve as power plants, turning food into adenosine triphosphate (ATP), the energy store chemical used to power cellular machinery. As a legacy of their bacterial origins, mitochondria carry their own DNA, separate from that in the cell nucleus. Making ATP is a messy business, creating all sorts of reactive molecules as byproducts, and that mitochondrial DNA is more vulnerable than the safely enclosed nuclear DNA. The balance of evidence strongly implicates mitochondrial DNA damage as one of the contributing causes of aging. A damaged gene can no longer be used as a blueprint for the process of gene expression that produces the protein machinery that is vital to the operation of a mitochondrion, and from there matters only go downhill - it's a long road that ends up at atherosclerosis, neurodegeneration, and many other forms of advanced age-related degeneration.
"Thus finding ways to repair mitochondrial DNA (mtDNA) is of great importance - but this is still a minority field of science in comparison to stem cell medicine or cancer research. Nonetheless, mitochondrial repair has been attracting some attention in the past week, as an important new line of research made it to the press release and publicity stage. The technique demonstrated is not really repair, per se, more a method of working around damage to mitochondrial genes - but it looks to be a great improvement over existing methodologies in terms of cost, time, and difficulty. This may enable broader and faster progress towards therapies that can remove the harm caused by damaged mitochondria.
"The new method is a way to deliver more or less arbitrary RNA to mitochondria, which should allow for continued function even after mutational damage to important genes. Production of RNA is a first step in the convoluted process of gene expression - by which genes are used as a blueprint for proteins - so it's quite possible to skip the gene and start with the RNA. This shortcut is the basis for a range of modern life science research, and one obvious use is to correct for a missing or damaged gene: find a way to provide the patient with an ongoing supply of suitably crafted RNA molecules targeted to the right places in his or her cells and it won't matter that the gene is broken.
"I should note that there are only thirteen genes in the mitochondria that are important for the purposes of this discussion, but the process of producing repairs or workarounds for each one has been hard, very different for each of them, slow, and difficult up until this point. A method that works in a very similar way for all of them is a big deal."
ANOTHER OF THE CRYONICS PIONEERS IS CRYOPRESERVED
The people who founded the cryonics movement in the late 60s and early 70s are being cryopreserved, one by one. The latest was Fred Chamberlain, co-founder of cryoncis provider Alcor:
"The first generation of the modern cryonics community, people who were middle-aged in the 1970s, is benefiting from the technologies and visions that they built. They founded a movement that has sustained itself for four decades in providing steadily improved cryopreservation services through organizations such as Alcor and the Cryonics Institute. The growth that would remake cryonics as from a non-profit community into a for-profit business with a healthy research and development arm has yet to happen, unfortunately, despite the clear need for the ability to preserve the brains and minds of those who will age to death before the advent of working rejuvenation biotechnology. But the present level of success is enough to provide a shot at renewed life in the future for the few who are determined enough and organized enough to take it.
"Fred Chamberlain III who, with his wife Linda, incorporated Alcor in 1972, was cryopreserved by Alcor on March 22, 2012. One week earlier, Fred relocated from Florida to a Scottsdale hospice. This allowed us to watch over him and respond immediately when needed. We believe that Fred received an excellent cryopreservation. More details will be released later.
"Fred Chamberlain was a NASA-JPL electrical engineer working on the Mariner-Jupiter-Saturn mission in 1973 [and] was and is of absolutely critical importance to cryonics. While most people with more than a passing acquaintance with cryonics will associate his importance with the founding of Alcor, that is in reality only a surrogate marker for his deeper importance. Fred came on the scene in cryonics in what was unarguably its darkest hour. It had degenerated into little more than a fraudulent cult in California and, everywhere in the US, it had lost all vestiges of technical and scientific rigor. When Fred discovered this in his role as Vice President of the Cryonics Society of California (CSC) he not only left CSC and founded Alcor, he and Linda Chamberlain established, for the first time anywhere, the practice of scientific, evidence based cryonics; cryonics based on the scientific method, on documentation of procedures, policies, cryopreservation protocols and rigorous patient case reports. He and Linda mandated not only scientific and technical accountability, but administrative, financial and legal accountability as well."
THEORIZING ON EVOLUTION AND LONGEVITY
Some thoughts on the bigger picture of evolution and longevity:
"The evolution of aging and longevity is a field in which it's still comparatively easy to make a mark and carve out an area of new theory. For most species it is still the case that ideas on their longevity are comparative unsettled: why they live as long as they do, what mechanisms may have determined their life span, and how it all fits in to the bigger picture of metabolism and the evolution of specific biological processes. There is far more data than any one group of researchers could hope to organize in a lifetime, and new information continues to flood in ever faster as the biotechnology revolution unfolds.
"At some point this rich wealth of data starts to give rise to hypotheses that are more holistic: evolution as a system of systems linked by feedback loops, thousands of species interacting with one another in any given biome, and the evolution of each species highly connected to that of its peers. Embarking upon this level of modeling and understanding, all the way down to biomolecular processes, will keep evolutionary biologists busy for the next century or so, I'd imagine - and give them something to do with the staggering levels of computing power that will be available by that time.
"Here is an interesting open access paper that gives a hint of the shape of this sort of future research, whilst considering the evolution of longevity amongst interacting species ... the researchers propose that such things as the ability of rapamycin (produced by soil bacteria) to extend life in mice or the beneficial effects of mammalian bile acid on yeast life span are late manifestations of cross-species evolutionary processes that have been going on since the very earliest epoch of multicellular life. The suggestion is that we should expect there to be a wide range of compounds produced by varied species that will have some beneficial effect on the life span of another species (such as by improving cellular housekeeping processes), because the existence of such relationships between species is a fundamental characteristic of diverse ecosystems produced by evolution."
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!
LATEST HEADLINES FROM FIGHT AGING!
AN INTERVIEW WITH DMITRY ITSKOV OF RUSSIA 2045
Friday, March 23, 2012
The founder of the Russia 2045 initiative is interviewed here: "Dmitry Itskov is the founder of Global Future 2045, which recently held its first conference. The Russian entrepreneur gathered scientists from around the world to discuss many topics that will help achieve one goal: life extension. ... The main idea of the project and my mission is to help people, to eliminate disease and death probably in the future, to overcome the limitations of our body, and to help humanity grow out of the crisis. As for my personal background, I have always been in the IT business, internet technologies. I published a few internet newspapers in Russia, I produce internet TV channel, a kind of blog service, email service, so being in this business I have always been interested in science and technologies that can extend life. Of course, like anybody, I have seen death and diseases in my family, my grandparents have gone, I've always been thinking how can I personally help. I've also been interested in science and I've seen an example of scientists who haven't gone, who are with us, like Stephan Hawking. He can't even move, he can't even normally talk to people, so this experience inspired me, this made me think how can I participate and help people. I decided to launch such an initiative with the help of Russian scientists who I knew like me. What helped me was that talking to them I was pretty sure that if we launched a kind of a big technical project, a big social initiative, if we work together, if we make our thinking global, and if we are able to launch a global network, then there is a very big chance we make our dreams come true. ... [The Avatar initiative] is the main technological project of the initiative which consists of four steps. One is human-like robot controlled by brain-computer interface. ... the second part is about producing life support system for the human brain. ... The third part is reverse engineering for the brain." The fourth step is to replace the biological brain with an artificial system that is more durable and extendable - which is a long way out, but something that has to be accomplished carefully and thoughtfully to be anything other than an expensive form of suicide that happens to leave behind a copy of the original you. Acceptable means include slowly replacing neurons one by one with nanomachinery that replicates their function and data storage whilst interfacing with the remaining brain tissue - but again, this sort of technology is a long way out from where we stand now, and there are many other challenges to be overcome along the way.
TRANSDIFFERENTIATION TO SIMPLIFY GENERATION OF CELLS TO ORDER
Friday, March 23, 2012
Researchers are slimming down the process of generating specific types of cell to order, turning the multi-step induced pluripotency processes of the last couple of years into a single step: researchers "have succeeded in obtaining somatic stem cells from fully differentiated somatic cells. [Scientists] took skin cells from mice and, using a unique combination of growth factors while ensuring appropriate culturing conditions, have managed to induce the cells' differentiation into neuronal somatic stem cells. ... Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage. Thanks to this new approach, tissue regeneration is becoming a more streamlined - and safer - process. ... One factor in particular, called Brn4, which had never been used before in this type of research, turned out to be a genuine 'captain' who very quickly and efficiently took command of his ship - the skin cell - guiding it in the right direction so that it could be converted into a neuronal somatic stem cell. ... This interconversion turns out to be even more effective if the cells, stimulated by growth factors and exposed to just the right environmental conditions, divide more frequently. ... Gradually, the cells lose their molecular memory that they were once skin cells. ... It seems that even after only a few cycles of cell division the newly produced neuronal somatic stem cells are practically indistinguishable from stem cells normally found in the tissue. ... So far, insights are based on experiments using murine skin cells; the next steps now are to perform the same experiments using actual human cells. In addition, it is imperative that the stem cells' long-term behaviour is thoroughly characterized to determine whether they retain their stability over long periods of time."
AN UPDATE ON BACTERIAL AGING
Thursday, March 22, 2012
The aging of bacteria has been a topic of interest in the years since its discovery; firstly, it overturns the long-held assumption that bacteria are essentially immortal, and secondly it provides insight into the very early evolutionary origins of aging. Here is a recent update: "Evidence for aging in symmetrically dividing bacteria such as Escherichia coli has historically been conflicting. Early work found weak or no evidence. More recent studies found convincing evidence, but negative results are still encountered. Because bacterial aging is believed to result from non-genetic (e.g. oxidative) damage, we tested the possibility that the negative outcomes resulted from the lack of an extrinsic damage agent. We found that streptomycin, which produces mistranslated proteins that are more vulnerable to oxidation, was able to induce both damage and aging in bacterial populations. A dosage effect relating the level of damage to the concentration of streptomycin was observed. Our results explain the previous inconsistencies because all studies that failed to find evidence for bacterial aging did not use a damage agent. However, all studies that succeeded in finding evidence utilized fluorescent proteins as a visual marker. We suggest that aging in those studies was induced by the harmful effects of an extrinsic factor, such as of the proteins themselves or the excitation light. Thus, all of the previous studies can be reconciled and bacterial aging is a real phenomenon. However, the study and observation of bacterial aging requires the addition of an extrinsic damage agent."
POPULAR PRESS ON ORGAN REGROWTH
Thursday, March 22, 2012
A BBC News article: "It might seem unbelievable, but researchers can grow organs in the laboratory. There are patients walking around with body parts which have been designed and built by doctors out of a patient's own cells. ... There is a pressing need. A shortage of available organs means many die on waiting lists and those that get an organ must spend a lifetime on immunosuppressant drugs to avoid rejection. The idea is that using a patient's own stem cells to grow new body parts avoids the whole issue of rejection as well as waiting for a donor. ... Dr Anthony Atala [has] made breakthroughs in building bladders and urethras. He breaks tissue-building into four levels of complexity. 1) Flat structures, such as the skin, are the simplest to engineer as they are generally made up of just the one type of cell. 2) Tubes, such as blood vessels and urethras, which have two types of cells and act as a conduit. 3) Hollow non-tubular organs like the bladder and the stomach, which have more complex structures and functions. 4) Solid organs, such as the kidney, heart and liver, are the most complex to engineer. They are exponentially more complex, have many different cell types, and more challenges in the blood supply. ... We've been able to implant the first three in humans. We don't have any examples yet of solid organs in humans because its much more complex. ... One of the problems when you move to larger organs is the getting the blood supply to work, connecting arteries, capillaries and veins to keep the organ alive. It is why some researchers are investigating 'decellularisation' - taking an existing donated organ, stripping out the original cells and replacing them with new cells from the patient who will receive the organ."
AN OUTSIDER'S OVERVIEW OF CRYONICS, PART II
Wednesday, March 21, 2012
The second part of an article in CMAJ that shows off some of the subtle prejudices against cryonics that exist in the medical scientific community (such as in the choice of title) while attempting objectivity: "Although death and taxes are said to be the only two certainties in life, a small but vocal community takes issue with the inclusion of the former. There is, they say, the alternative of cryonics, in which a legally dead person is preserved at -196C in hopes that he will ultimately be revived and rejuvenated, once a cure for his ailment is found. And it's entirely consistent with the basic tenets of medicine, providers argue. ... Although it seems like an unusual and radical idea to many people, I think in the very truest sense of the term, this is conservative medicine. This is literally conserving a patient rather than giving up on them by today's standards of medicine. It's true a doctor can't do anything more for these people, but that doesn't mean the future cannot. ... Those interested in cryonics tend be optimistic, hopeful about technological developments and dissatisfied with an ordinary life span, says Ben Best, president of the Cryonics Institute. ... a miniscule chance is better than none, enthusiasts say. ... Nobody has come up with a better idea yet, so therefore myself, as well as some others, believe that cryonics is simply the second worst thing that can happen. You're going to die. You're going to stop breathing. Whether you be buried or cremated or cryopreserved, it's going to happen. There's nothing we can do about this now, but I know that if I'm cremated or buried, even if technology vastly increased, I'm never coming back. ... Enthusiasts are mystified that only a small segment of the general population has investigated the cryonic option. ... I don't know why there are far more people who don't sign up for cryonics arrangements. It's true that what we do is unorthodox and different, at least in 2012. But there are so many bizarre ideas out there which have no evidence to support them and get many, many people fascinated ... Yet we only have less than 1000 members after 40 years. ... People tend in my experience to kind of rely on this naturalistic [fallacy] that because people have always gotten older and died, therefore they should get older and die as a result of simply living longer."
VERNOR VINGE ON RADICAL LIFE EXTENSION
Wednesday, March 21, 2012
From an interview with Vernor Vinge at Wired: "First of all, I'm all for human life extension. In The Singularity is Near, I think, [Ray Kurzweil] has a nice discussion of the situation that a lot of essayists have where they say, 'Oh, we really don't want that. A wise and philosophical person realizes that life needs be limited, and that's a good thing,' these essayists say. He does a good job of criticizing that point of view, and I certainly agree with that. Furthermore, I think that a human lifespan of a thousand years with post-Singularity technology is easily doable. I think a lifespan of a thousand years would actually - Singularity aside - would do human society and human nature a great deal of good, and don't think it is that difficult, it probably can even be achieved without having a Technological Singularity. Life spans of 10,000 to 100,000 years, then you begin to look at what's involved, the humans that are involved, and how capable a human mind is of absorbing variety. ... The complaint or the criticism here is that the human mind has a certain level of ability to handle different sorts of complexity, and if you believe that you could go 100,000 years and not be turned into a repeating tape loop, well, then let's talk about longer period of time. How about a billion years, or a hundred billion years? At a hundred billion years, you're out there re-engineering the universe. The age of the universe becomes your chief longevity problem. But there's still the issue of, what would it be like to be you after that? This raises the point, which actually I'm sure is also on Ray's mind, that if you're going to last that long you have to become something greater, and the Singularity is ideally set up to supply that. So the people who are into the intelligence amplification mode of looking at these things, this all fits. And I'm not saying that in a critical and negative way, it does all fit, and it puts you in a situation where you are talking realistically about living very long periods of time, perhaps so long that you have to re-engineer the universe because the universe is not long-lived enough. At the same time, you have to be growing and growing and growing. I mean, intellectually growing. Now, if you look at that situation, it ultimately gets you, I think, to a very interesting philosophical point, which really I don't think was within the horizon of what people normally thought about two or three or four hundred years ago."
ROUTINE PERIODIC FASTING LOWERS DISEASE RISK
Tuesday, March 20, 2012
Here is more evidence for modest benefits derived from common forms of minimal intermittent fasting, though as is often the case one may suspect that other associations with lifestyle choices cloud the picture: "Previously we discovered that routine periodic fasting was associated with a lower prevalence of coronary artery disease (CAD). Other studies have shown that fasting increases longevity in animals. A hypothesis-generating analysis suggested that fasting may also associate with diabetes. This study prospectively tested whether routine periodic fasting is associated with diabetes mellitus (DM). Patients (n = 200) undergoing coronary angiography were surveyed for routine fasting behavior before their procedure. ... Meta-analyses were performed by evaluation of these patients and 448 patients from a previous study. DM was present in 10.3% of patients who fasted routinely and 22.0% of those who do not fast. CAD was found in 63.2% of fasting and 75.0% of nonfasting patients, and in nondiabetics this CAD association was similar. Meta-analysis showed modest differences for fasters versus nonfasters in glucose concentrations (108 ± 36 vs 115 ± 46 mg/dl) and BMI (27.9 ± 5.3 vs 29.0 ± 5.8 kg/m(2)). In conclusion, prospective hypothesis testing showed that routine periodic fasting was associated with a lower prevalence of DM in patients undergoing coronary angiography. A reported fasting association with a lower CAD risk was also validated and fasting associations with lower glucose and BMI were found."
AN EXAMPLE OF CANCER IMMUNOTHERAPY DEVELOPMENT
Tuesday, March 20, 2012
Another promising form of immunotherapy in mice: "researchers have trained mouse immune systems to eradicate skin cancer from within, using a genetic combination of human DNA from melanoma cells and a cousin of the rabies virus. The strategy, called cancer immunotherapy, uses a genetically engineered version of the vesicular stomatitis virus to deliver a broad spectrum of genes derived from melanoma cancer cells directly into tumors. In early studies, 60 percent of tumor-burdened mice were cured in fewer than three months and with minimal side effects. ... We believe that this new technique will help us to identify a whole new set of genes that encode antigens that are important in stimulating the immune system to reject cancer. In particular, we have seen that several proteins need to be expressed together to generate the most effective rejection of the tumors in mice. ... The immune system functions on a seek-and-destroy platform and has fine-tuned its capacity to identify viral invaders such as vesicular stomatitis virus. Part of the appeal of building cancer vaccines from the whole spectrum of tumor DNA is that tumors can adapt to the repeated attacks of a healthy immune system and display fewer antigens (or signposts) that the immune system can identify. Cancers can learn to hide from a normal immune system, but appear unable to escape an immune system trained by the vesicular stomatitis virus with the wide range of DNA used in the library approach. ... Nobody knows how many antigens the immune system can really see on tumor cells. By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system. The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated."
AN OUTSIDER'S OVERVIEW OF CRYONICS
Monday, March 19, 2012
If you read the whole thing, this outsider's view of cryonics at CMAJ illustrates a few of the subtle prejudices held in the medical and scientific community in the course of trying to be objective: "cryonics - the practice of preserving a legally dead person at a temperature far below freezing in hopes of someday being revived and rejuvenated after advances in science have provided a cure for their ailment. The appeal is self-evident, enthusiasts say. 'It certainly offers an opportunity, although remote and probably speculative, as an ambulance to the future so to speak. If I die from something that is not preventable today, maybe future technology will offer the means of reviving me, figuring out the condition I have and fixing it.' Yet, however appealing the notion of a second life may be, the number of people who've actually been frozen is miniscule: about 250, according to the Cryonics Institute, a cryonics services provider located in a regional township of the state of Michigan. ... But far more people appear interested in being frozen. Membership in the two biggest cryonics providers in the United States - the Cryonics Institute and the Alcor Life Extension Foundation in Scottsdale, Arizona - is close to 2000. ... The cryonics process involves draining a patient's fluids and replacing them with a vitrification solution, essentially a preservative cocktail of cryoprotectant chemicals such as dimethylsulfoxide, ethylene glycol, propylene glycol and glycerol that are believed to prevent ice crystal formation and reduce the extent of tissue damage that occurs after flesh is frozen. The corpse is allowed to cool and then dropped into liquid nitrogen for indefinite preservation at a brisk -196°C. Or as Ben Best, president of the Cryonics Institute, writes in an email 'the perfusion process involves replacing body water in cells, not just blood in the blood stream. By perfusing vitrification solution into the blood stream, there is an exchange of vitrification solution for water. Water is removed from the body (and tissues) as vitrification solution replaces it by the diffusion process. With vitrification solution in brain tissue (especially) there should be no ice formation whatsoever. The flesh is therefore vitrified, not frozen (freezing means ice). The patient is cooled under a computer controlled cooling box to liquid nitrogen temperature, not simply 'dropped' in liquid nitrogen.'"
SENS FOUNDATION ON RECENT MITOCHONDRIAL RESEARCH
Monday, March 19, 2012
The SENS Foundation here comments on recent research that may make it easier to build therapies to treat mitochondrial DNA damage in order to remove its contribution to aging: "The UCLA group's approach is highly promising. Their work builds upon and may potentially supersede several previous approaches to the problem of mitochondrial mutations that occur as a result of the degenerative aging process, including allotopic protein expression, its optimization using [a mitochondrial targeting sequence], and the exploitation of the multiprotein RNA import complex (RIC) of the protozoal parasite Leishmania tropica (which the investigators characterize as 'requir[ing] the introduction of nonnative tRNAs with foreign protein factors or the transfer of a large multisubunit aggregate into cells, which is of low efficiency and difficult to reproduce in desirable disease-relevant settings' ... As compared to allotopic protein expression, an RNA-based approach has the theoretical advantage of abrogating the difficulties encountered thus far with the mitochondrial import of large and hydrophobic proteins. But as we suggested in discussion of their earlier, more discovery-phase research, allotopic protein and RNA approaches are not mutually exclusive: different mitochondrially-encoded proteins could be either allotopically expressed, or their mRNAs generated allopically and imported for in situ translation, depending on the ease or efficiency of each approach for the protein in question. ... For their part, Dr. Teitell's group is evidently optimistic, and have clearly moved beyond the basic science focus of their earlier report. ... In response to this report, SENS Foundation CSO Dr. Aubrey de Grey has said that 'If this is as good as it looks, I think it could be a real game-changer', and Dr. O'Connor and his team at the SENS Foundation RC are considering testing a construct based on Teitell's methods in a system that the RC has already generated and used for testing of allotopic expression of cytochrome B. The race is on -- as it should be, for the stakes are large. Large, age-related deletions in mtDNA are likely responsible for the systemic rise in oxidative stress with aging, and for localized but terrible pathologies of skeletal muscle and substantia nigra dopaminergic neurons in aging bodies. The obviation of these mutations is a desperate medical need, and biomedicine is shamed for every day that a solution is delayed. This new method must be tested and exploited to its limits, and all approaches must be trialed, until the fires of life are once again burning in rejuvenated cells, in bodies restored to their youthful prime."