Fight Aging! Newsletter, September 12th 2011

September 12th 2011

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!



- First Videos From SENS5
- A Primer on Compression of Morbidity
- Predictions are Hard
- Carving Named Diseases from the Concept of Aging
- Why Research the Biology of Non-Mammals?
- Discussion
- Latest Headlines from Fight Aging!


The SENS5 conference held at the start of the month didn't produce much live coverage online, but the first presentation videos are now being be posted:

"SENS5, the fifth biannual conference on the Strategies for Engineered Negligible Senescence, took place last week. Researchers working on ways - or the foundation of ways - to intervene in the aging process gathered together to talk about progress on the road to rejuvenation through biotechnology. ... It seems, however, that the participants were so caught up in the conference schedule that they largely failed to post reports or commentaries online. ... Perhaps this is a sign of maturity for the internet: later years in which eager self-publishers feel they can let their hair down and stop trying quite so hard. Material will be posted online in the weeks ahead by SENS Foundation volunteers."

A YouTube channel for official conference videos exists, and will be filling up as formatting is accomplished by SENS Foundation volunteers:


If you read around the literature on aging research, sooner or later you'll run into the compression of morbidity hypothesis. Here is an introduction:

"It is a hypothesis suggesting that advances in medical science are causing, or will cause, a compression of the terminal period of frailty, illness, and disability at the end of life, squeezing it into an ever-shorter fraction of the overall human life span. In colloquial use compression of morbidity is spoken of as a practical goal by medical researchers who do not wish to talk openly about extending human life for political or funding reasons."


So when will functional rejuvenation biotechnology arrive? That is the all-important question, given that none of us are getting any younger:

"Making predictions is hard, as the joke goes, and especially when they involve the future. That said, predicting very broad trends and general capabilities in technology seems to be somewhat tractable if you go about it in the right way, such as by researching carefully and restricting your predictions to the future capabilities of fields that present have a solid research community: large, well funded, and well supported. Even so, making specific predictions as to how future capabilities will be used is a fool's game.

"I would say that the principal cause of uncertainty for the timeline leading to rejuvenation biotechnology - ways to repair and reverse the cellular and molecular damage that causes aging - is the fact that we lack a large, well-funded, well-supported research community at this time. Only comparatively small initiatives exist now, such as the SENS Foundation, and the actions, choices, and happenstance of individuals have large effects on the future timeline leading to the desired solid research community. That future community will be large enough that individual choices don't tend to have much of an effect on its progress one way or another, but here and now the element of chance is significant.

"So it is much easier to look at, say, the regenerative medicine research community and make solid, well-thought predictions as to when we'll see limbs and organs regrown. Similar, one can plant flags on the field for rejuvenation biotechnology if we restrict ourselves to talking about how long things might take after large numbers of dollars, supporters, and willing scientists arrive on the scence. That's thought to be ten to twenty years and one to two billion dollars to rejuvenate old mice if you're looking at the SENS plan. But how long until the necessary dollars, supporters, and willing scientists arrive? How long is a piece of string? The bootstrapping process of persuasion and fundraising goes as rapidly as it can be made to go."


A look at the culture of aging research:

"Seen from a considered distance, the culture of aging research - formed of researchers, regulators, and the interested public - operates in strange ways. No-one is permitted to treat aging: by decree of the regulators and complicity of the researchers that is taboo. But slow progress in treating aging is made nonetheless. That technological progress goes hand in hand with an intricate cultural dance that consists of splitting off pieces of the concept of aging and giving each piece a different and distinct name ('Alzheimer's disease,' 'osteoarthritis,' 'sarcopenia,' and so forth). Once such a sliver of aging is named and fully accepted, it is no longer taboo to work towards treating it.

"To a certain degree, culture shapes the progress of medical science. Strategies for repairing aging outright by focusing on common low-level molecular changes - like Engineered Negligible Senescence - don't mesh well with the structure of the mainstream culture of aging research, and so face an uphill battle to win greater adoption. Repair strategies do away with the whole business of parceling up a collection of end-stage symptoms of aging and declaring them a disease, and focus instead on a different vision for aging and the treatment of aging from the bottom up. Long-standing cultures are resistant to change, however, and especially resistant to radical change. That is far from the only hurdle in the way of progress, and the existence of centralized control over medicine and heavy regulation has a lot more to answer for than odd cultural ideas about how things should work, but those odd ideas are still a factor."


Researchers spend a great deal of time on the biology of aging in species of fly, worm, fish, and even yeast. Why not work in mice all the time?

"The answer to that question relates to the bottom line: money, time, resources. Research is by its very nature an exploratory and uncertain business, full of dead ends and unexpected pitfalls. A researcher wants to cover as much ground as he or she can for a given amount of time and money: the more that is explored, the greater the chance of finding a significant path forward. On the one hand, work with mammals will generally produce more useful information, but on the other hand working with mammals, even mice, is very expensive and time-consuming in comparison to working with flies and worms, which in turn is expensive and time-consuming in comparison to working with yeast. If infinite money and time were at hand, all research work would involve mammals, but resources are not infinite and the results of any given study are extremely uncertain. ... So the story is that there is a trade-off in the life sciences between the usefulness of data and the cost of obtaining that data. When you are uncertain of the ultimate value of the work presently being undertaken - i.e. if it seems to have a high risk of failure, or a successful outcome is probably not that valuable in any case - then you won't want to spent much time and money on it until such time as it shapes up. If all indications show a good chance of success and a valuable result, then working with mammals starts to look like a better prospect, however. So we might say that work in flies, worms, yeast, and fish is undertaken in order to justify the cost of exploring the same biology in mammals."


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!



Friday, September 9, 2011
Polyamines have been of interest since spermadine was shown to extend life in mice. Another topic of growing interest is the influence of gut bacteria on metabolism and longevity, and here is research to link these two items: "In mammals, levels of polyamines (PAs) decrease during the ageing process; PAs are known to decrease systemic inflammation by inhibiting inflammatory cytokine synthesis in macrophages. ... The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations. ... We supplemented the diet of 10-month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls received no supplementation. Survival rates were compared [and] LKM512-treated mice survived significantly longer than controls; moreover, skin ulcers and tumors were more common in the control mice." A caution here is that this result may well involve inadvertent calorie restriction: any dietary supplementation may affect appetite and thus level of caloric intake, and all studies have to be considered in light of the fact that even mild calorie restriction has beneficial effects on mouse health and life span.

Friday, September 9, 2011
Via ScienceDaily: researchers "have unveiled a new method for making synthetic collagen. The new material, which forms from a liquid in as little as an hour, has many of the properties of natural collagen and may prove useful as a scaffold for regenerating new tissues and organs from stem cells. ... Our final product more closely resembles native collagen than anything that's previously been made, and we make that material using a self-assembly process that is remarkably similar to processes found in nature. ... Collagen, the most abundant protein in the body, is a key component of many tissues, including skin, tendons, ligaments, cartilage and blood vessels. Biomedical researchers in the burgeoning field of regenerative medicine, or tissue engineering, often use a combination of stem cells and collagen-like materials in their attempts to create laboratory-grown tissues that can be transplanted into patients without risk of immunological rejection. Animal-derived collagen, which has some inherent immunological risks, is the form of collagen most commonly used in reconstructive and cosmetic surgery today. ... Despite the abundance of collagen in the body, deciphering or recreating it has not been easy for scientists. One reason for this is the complexity collagen exhibits at different scales. ... Scientists must next determine whether cells can live and grow in the new material and whether it performs the same way in the body that native collagen does. ... clinical trials, if they prove warranted, are at least five years away."

Thursday, September 8, 2011
It is now fairly well known that any animal study of longevity has to be controlled for calorie restriction, as the effects of even a modest change in dietary intake can outweigh the intended effects of the study, rendering the results useless. This is far from the only confounding factor out there, however. Here is some work on a different issue that might be problematic for longevity studies in worms: "The nematode worm Caenorhabditis elegans has been used to identify hundreds of genes that influence longevity and thereby demonstrate the strong influence of genetics on lifespan determination. In order to simplify lifespan studies in worms, many researchers have employed 5-fluoro-2'-deoxyuridine (FUdR) to inhibit the development of progeny. While FUdR has little impact on the lifespan of wild-type worms, we demonstrate that FUdR causes a dramatic, dose-dependent, twofold increase in the lifespan of the mitochondrial mutant gas-1. Thus, the concentration of FUdR employed in a lifespan study can determine whether a particular strain is long-lived or short-lived compared to wild-type." This sort of thing is one of the many reasons why it is better to weigh evidence across many studies and to be skeptical of any one study in isolation.

Thursday, September 8, 2011
Via EurekAlert!: "Any exercise that gets the heart pumping may reduce the risk of dementia and slow the condition's progression once it starts ... Researchers examined the role of aerobic exercise in preserving cognitive abilities and concluded that it should not be overlooked as an important therapy against dementia. The researchers broadly defined exercise as enough aerobic physical activity to raise the heart rate and increase the body's need for oxygen. Examples include walking, gym workouts and activities at home such as shoveling snow or raking leaves. ... We culled through all the scientific literature we could find on the subject of exercise and cognition, including animal studies and observational studies, reviewing over 1,600 papers, with 130 bearing directly on this issue. We attempted to put together a balanced view of the subject. We concluded that you can make a very compelling argument for exercise as a disease-modifying strategy to prevent dementia and mild cognitive impairment, and for favorably modifying these processes once they have developed. ... The researchers note that brain imaging studies have consistently revealed objective evidence of favorable effects of exercise on human brain integrity. Also, they note, animal research has shown that exercise generates trophic factors that improve brain functioning, plus exercise facilitates brain connections (neuroplasticity). ... Whether addressing our patients in primary care or neurology clinics, we should continue to encourage exercise for not only general health, but also cognitive health."

Wednesday, September 7, 2011
A modest new application of stem cells in therapy: researchers "have used a new, leading-edge stem cell therapy to promote the growth of bone tissue following the removal of cervical discs - the cushions between the bones in the neck - to relieve chronic, debilitating pain. [The procedure] used bone marrow-derived adult stem cells to promote the growth of the bone tissue essential for spinal fusion following surgery, as part of a nationwide, multicenter clinical trial of the therapy. ... We hope that this investigational procedure eventually will help those who undergo spinal fusion in the back as well as in the neck, and the knowledge gained about stem cells also will be applied in the near future to treat without surgery those suffering from back pain. ... In the surgery, called an anterior cervical discectomy, a cervical disc or multiple discs are removed via an incision in the front of the neck. The investigational stem cell therapy then is applied to promote fusion of the vertebrae across the space created by the disc removal. ... [Using existing methods], adequate spinal fusion fails to occur in 8 to 35 percent or more of patients, and persistent pain occurs in up to 60 percent of patients with fusion failure, which often necessitates additional surgery. ... A lack of effective new bone growth after spine fusion surgery can be a significant problem, especially in surgeries involving multiple spinal segments. This new technology may help patients grow new bone, and it avoids harvesting a bone graft from the patient's own hip or using bone from a deceased donor."

Wednesday, September 7, 2011
Autophagy is important in longevity, and research groups are investigating this process with an the intent of developing ways to safely manipulate it: "two cellular processes - lipid metabolism and autophagy - work together to influence worms' lifespan. Autophagy, a major mechanism cells use to digest and recycle their own contents, has become the subject of intense scientific scrutiny over the past few years, particularly since the process (or its malfunction) has been implicated in many human diseases, including cancer and Alzheimer's disease. This study provides a more detailed understanding of the roles autophagy and lipid metabolism play in aging. ... The particular worm model we used in this study is known to live longer than normal worms, but we didn't completely understand why. Our results suggest that increased autophagy has an anti-aging effect, possibly by promoting the activity of a fat-digesting enzyme. In other words, it seems that recycling fat is a good thing - at least for worms. ... When worms have more fat in supply than they have demand for, it has to be stored. In these long-lived worms however, there's activation of a seemingly futile cycle of breaking down fat and re-synthesizing it. Only we found that breaking down fat is actually beneficial and perhaps not so futile after all. ... On average, they survived 25 percent longer than their normal counterparts."

Tuesday, September 6, 2011
Guanfacine is a drug used to manipulate signaling mechanisms shown to improve working memory in monkeys. Here is some further work on this topic: "Alpha-2 adrenergic receptors are potential targets for ameliorating cognitive deficits associated with aging as well as certain pathologies such as attention deficit disorder, schizophrenia and Parkinson's disease. Although the alpha-2 agonist guanfacine has been reported to improve working memory in aged primates, it has been difficult to assess the extent to which these improvements may be related to drug effects on attention and/or memory processes involved in task performance. The present study investigated effects of guanfacine on specific attention and memory tasks in aged monkeys. Four Rhesus monkeys (18-21 years old) performed a sustained attention (continuous performance) task and spatial working memory task (self-ordered spatial search) that has minimal demands on attention. Effects of a [low and high] dose of gunafacine were examined. Low-dose guanfacine improved performance on the attention task but failed to improve performance on the spatial working memory task. The high dose of guanfacine had no effects on either task. Guanfacine may have a preferential effect on some aspects of attention in normal aged monkeys and in doing so may also improve performance on other tasks, including some working memory tasks that have relatively high attention demands."

Tuesday, September 6, 2011
An investigation of the role of growth hormone in the regenerative capacity of zebrafish: "Unlike mammals, teleost fishes are capable of regenerating sensory inner ear hair cells that have been lost following acoustic or ototoxic trauma. Previous work indicated that immediately following sound exposure, zebrafish saccules exhibit significant hair cell loss that recovers to pre-treatment levels within 14 days. Following acoustic trauma in the zebrafish inner ear, we used microarray analysis to identify genes involved in inner ear repair following acoustic exposure. Additionally, we investigated the effect of growth hormone (GH) on cell proliferation in control zebrafish utricles and saccules, since GH was significantly up-regulated following acoustic trauma. ... Pathway Analysis software was used to reveal networks of regulated genes and showed how GH affected these networks. Subsequent experiments showed that intraperitoneal injection of salmon growth hormone significantly increased cell proliferation in the zebrafish inner ear. ... GH injection increased cell proliferation in the inner ear of non-sound-exposed zebrafish, suggesting that GH could play an important role in sensory hair cell regeneration in the teleost ear."

Monday, September 5, 2011
The development of engineered viruses to selectively attack cancer has been underway for a number of years, and here is an example of an early trial for one strand of this research: "Scientists modified the vaccinia virus, which is more famous for being used to develop a smallpox vaccine. The virus, named JX-594, is dependent upon a chemical pathway, common in some cancers, in order to replicate. It was injected at different doses into the blood of 23 patients with cancers which had spread to multiple organs in the body. In the eight patients receiving the highest dose, seven had the virus replicating in their tumours, but not in healthy tissue. ... We are very excited because this is the first time in medical history that a viral therapy has been shown to consistently and selectively replicate in cancer tissue after intravenous infusion in humans. Intravenous delivery is crucial for cancer treatment because it allows us to target tumours throughout the body as opposed to just those that we can directly inject. ... Infection prevented further tumour growth in six patients for a time. However, the virus did not cure cancer. Patients were given only one dose of the virus as the trial was designed to test the safety of the virus. It is thought that the virus could be used to deliver treatments directly to cancerous cells in high concentrations. ... Viruses that multiply in just tumour cells - avoiding healthy cells - are showing real promise as a new biological approach to target hard-to-treat cancers."

Monday, September 5, 2011
Via EurekAlert!, news of research to complement recent work on tissue engineered intestines in mice: "Human colon stem cells have been identified and grown in a lab-plate for the first time. ... Throughout life, stem cells of the colon regenerate the inner layer of our large intestine in a weekly basis. For decades scientists had evidences of the existence of these cells yet their identity remained elusive. Scientists [discovered] the precise localization of the stem cells in the human colon and worked out a method that allows their isolation and in vitro expansion, that is their propagation in lab-plates. Growing cells outside the body generally requires providing the cells in a lab-plate with the right mix of nutrients, growth factors and hormones. But in the same way that each of the more than 200 types of cells in our body differs from the others so too do optimal growing conditions in the lab. ... For years, scientists all over the world have been trying to grow intestinal tissue in lab-plates; testing different conditions; using different nutritive media. But because the vast majority of cells in this tissue are in a differentiated state in which they do not proliferate, they survived only for a few days. ... The scientific community now has a defined 'recipe' for isolating CoSCs and deriving stable CoSCs lines, which have the capacity to grow undifferentiated for months. ... Now that guidelines for growing and maintaining colon stem cells in the lab are in place, we have an ideal platform that could help the scientific community to determine the molecular bases of gastrointestinal cell proliferation and differentiation. It is also suspected that alterations in the biology of CoSCs are at origin of several diseases affecting the gastrointestinal tract, such as colorectal cancer or Crohn's disease."



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