FIGHT AGING! NEWSLETTER
April 18th 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!
- Reverse Engineering of Protofection as a Vegas Group Goal
- An Update on Leishmania and Mitochondrial Repair
- Critiquing the Practice of Cryonics
- Latest Headlines from Fight Aging!
REVERSE ENGINEERING OF PROTOFECTION AS A VEGAS GROUP GOAL
The Vegas Group concept that I have discussed over past weeks continues to flesh out: a yet-to-be-built community initiative intended to bring longevity science to the open biotechnology and DIYbio communities - and from there reverse engineer and make ready for human use the most promising longevity-enhancing technologies demonstrated in mice in the laboratory.
"All journeys start with the first steps, and I'm in favor of incremental approaches to development. Make something small, a minimum viable product that is the most elementary building block that can stand on its own and still contribute to the ultimate goal. ... From the broad high level outline of the Vegas Group, I focused on the codex: the necessary how-to documents and body of knowledge that will enable people to participate. ... a fairly narrow initial project for the codex must be identified, so that the first group of volunteers to work on it can run into all the brick walls and fall into all of the potholes without risking a great deal if it all fails. Small projects are easy to scrap, rework, and start over if necessary - and that is a tremendous advantage when you don't yet know the detailed recipe for success. ... What is this first codex project, though?
"I propose that reverse engineering and documentation of mitochondrial protofection is a good candidate. This is a technique by which mitochondrial DNA is replaced throughout an individual's cells, and was first demonstrated in mice back in 2005. As you might know, progressively accumulated damage to mitochondrial DNA is one of the causes of aging, as described by the mitochondrial free radical theory of aging. Future rejuvenation biotechnology must include a way to either permanently work around this form of damage, such as through the methodology advocated by the SENS Foundation, or periodically repair it - say once every two to three decades."
"Why protofection? In a nutshell: (a) It is comparatively easy to explain to a non-technical audience. (b) It fits with the SENS vision for rejuvenation biotechnology. (c) It has already been demonstrated to work, so at least one group of researchers knows exactly how to do it. (d) It is old enough that this and related knowledge may have spread somewhat, making it more amenable to reverse engineering."
A mailing list opened a few days ago for further discussion on how to make the Vegas Group a reality. By all means join if you're interested or can contribute:
AN UPDATE ON LEISHMANIA AND MITOCHONDRIAL REPAIR
While we're on the subject of repairing mitochondrial DNA, here is an update on progress in the development of a different methodology, distinct from both protofection and the SENS Foundation approach of copying important mitochondrial genes into the cell nucleus:
"Dr. Samit Adhya of the Division of Molecular and Human Genetics at the Indian Institute of Chemical Biology is pursuing yet another innovative approach. He proposes to dispense with the need for mitochondrial DNA altogether, by instead providing the mitochondrial protein-making machinery directly with the 'working instructions' (messenger RNA) that it normally receives in the form of a transcribed copy taken from the mitochondrial DNA originals. This would allow the mitochondria to continue their protein production even if the mitochondrial DNA were completely destroyed.
"[The latest news is that] Samit Adhya and company took mutant cells with massively broken mitochondrial DNA and temporarily fixed their operation by providing them with doses of RNA tailored to create the protein components that their damaged DNA couldn't produce. ... The therapeutic potential [should] now be tested in animal models of inherited mitochondrial disease, [and] if successful, the more ambitious work of using it to restore [cells become damaged] as a result of the degenerative aging of wild-type mice. The biomedical rejuvenation of aging human mitochondrial function would not lie far behind, with the promise of muscles maintained, Parkinson's prevented, and an end to the rising systemic metabolic toxicity of [cells overrun with damaged mitochondria]."
It looks like a few more years will pass before we see this methodology tested in mice rather than in cells only.
CRITIQUING THE PRACTICE OF CRYONICS
A weighty set of articles are linked from the Fight Aging post below:
"Over at Chronosphere you'll find a weighty set of posts that aim to provide a foundation for critiquing cryonics at the organizational level of achieving consistently good cryopreservations, and the development of professional organizational cultures and processes - such as record-keeping - required to support that goal. All industries require ongoing initiatives that provide solid, constructive critiques of present practice, for otherwise how are the participants to progress and improve themselves? ... The goal of this series of articles is to equip the reader with the tools necessary to make an accurate assessment of the quality of care cryonics patients, both individually and as a group, are receiving from their respective cryonics organizations."
The articles touch on a number of important items: in particular cryonics as a service is presently a product that requires a great deal of due diligence and ongoing work on the part of the purchaser. It's more like organizing a party than buying a ticket to one - and this, I think is one of the barriers to growth in cryonics. Somewhere in the future lies a form of full service cryonics provider that makes it much easier for people to sign up, manage the service, and organize the end of life issues that can tangle an otherwise successful cryopreservation. See, for example, this post from the archives:
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!
CALORIE RESTRICTION AND CORE BODY TEMPERATURE IN HUMANS
Friday, April 15, 2011
Another of the observed effects of calorie restriction in lower animals is shown to exist in humans as well: "Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. ... Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups ... Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging."
INDUSTRIALIZATION OF TISSUE ENGINEERING
Friday, April 15, 2011
Economies of scale apply to all endeavors, including the production of human tissue: "The high-tech production lines of [a] laboratory in Germany began moving this week turning out a unique product - human skin. Nicknamed 'The Flesh Factory' by the boffins who work at the Stuttgarter Fraunhofer-Institute, it aims to produce 5,000 circles of skin as big as a one-euro cent every month. Costing around 45 pounds each, when the skin circles are perfected they will be sold to hospitals and clinics around the world for life-saving operations. Project leader Professor Heike Walles, 48, has devoted her whole life to the goal of reproducing human skin on an industrial scale - to save human life and protect animals; it can be used for the kind of testing currently requiring the sacrifice of live creatures. ... Until now, methods of culturing tissue like that used for skin transplants have been very expensive. Most of the steps are carried out manually, which means that the process is not particularly efficient. ... The new production line is entirely mechanical and controlled by computers. ... The process works like this; a biopsy - a sample of human tissue - is checked for sterility. A gripper arm then transports the biopsy into an automated cutting device. The machine snips the biopsy into small pieces, isolates the different cell types, stimulates their growth, and mixes the skin cells with collagen. A three-dimensional reconstruction of the different skin layers is produced with the aid of a special gel matrix - and the skin is ready. In the final step, the machine packages the cells for shipment. Alternatively, the tissue can be cryopreserved - that is, deep-frozen and stored for later use."
VEGETARIANISM, OR LESS BODY FAT?
Thursday, April 14, 2011
Here is an example of a research commentary that misses the forest for the trees: "Vegetarians experience a 36 percent lower prevalence of metabolic syndrome than non-vegetarians, suggests new research ... Because metabolic syndrome can be a precursor to heart disease, diabetes, and stroke, the findings indicate vegetarians may be at lower risk of developing these conditions. Metabolic syndrome is defined as exhibiting at least three out of five total risk factors: high blood pressure, elevated HDL cholesterol, high glucose levels, elevated triglycerides, and an unhealthy waist circumference. ... while 25 percent of vegetarians had metabolic syndrome, the number significantly rises to 37 percent for semi-vegetarians and 39 percent for non-vegetarians. The results hold up when adjusted for factors such as age, gender, race, physical activity, calories consumed, smoking, and alcohol intake. ... On average, the vegetarians and semi-vegetarians were three years older than non-vegetarians. Despite their slightly older age, vegetarians had lower triglycerides, glucose levels, blood pressure, waist circumference, and body mass index (BMI). Semi-vegetarians also had a significantly lower BMI and waist circumference compared to those who ate meat more regularly." Given the broader context of what is known about the effects of body fat on long-term health, the plausible mechanism here looks to be related to the amount of visceral fat rather than anything to do with diet per se.
GROWING KIDNEYS FROM STEM CELLS
Thursday, April 14, 2011
Progress in tissue engineering: "scientists have created human kidneys from stem cells ... The artificial organs were created in a laboratory using human amniotic fluid and animal foetal cells. They are currently half a centimetre in length - the same size as kidneys found in an unborn baby. [Scientists] hope they will grow into full-size organs when transplanted into a human. ... It sounds a bit science fiction-like but it's not. The idea is to start with human stem cells and end up with a functioning organ. We have made pretty good progress with that. We can make something that has the complexity of a normal, foetal kidney ... The research team hope that doctors will eventually be able to collect amniotic fluid, which surrounds the growing embryo in the womb, when a baby is born. This will then be stored by scientists in case that person develops kidney disease later in life. The fluid can then be used to create a matching kidney. Creating an organ using a patient's own stem cells solves the problem of having to use powerful immunosuppressant drugs to stop the body rejecting a another person's kidney. ... the technology could be ready for use on humans in around 10 years." By which time it will probably be unnecessary to collect amniotic fluid, as the signals and chemicals it provides will be understood and reproduced.
KLOTHO IN HUMANS
Wednesday, April 13, 2011
You might recall the identification of klotho as a longevity-related gene in mice and other lower animals in recent years. Here is a study on levels of klotho in humans: "The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans. ... We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. ... During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho [had] an increased risk of death compared with participants in the highest tertile of plasma klotho ... In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans." Given the number of adjustments there, I'd like to see a confirming study - and for preference one that explicitly took into account calorie intake as well. Just because you see the expected result is no reason to abandon the usual level of caution needed when reading the output of the scientific method.
NEVER TOO LATE TO EXERCISE: THE PROOF STUDY
Wednesday, April 13, 2011
Even at older ages, exercise is a still very important - as demonstrated by the degree to which it influences ongoing health in later stages of life, just as it does in earlier stages in life. "It is not sufficient simply to live longer. One of the current priorities for public health is to how to maintain good quality of life for longer. This has given rise to the concept of 'successful aging' generating a turning point in our thinking about aging, which is no longer seen as an inevitable decline. ... Physical activity has a pleiotropic effect and is a significant factor in successful aging. This study aims to quantify the relationship between the physical activity of a 65-year-old cohort and the level of life satisfaction and self-rated health 7 years later. A total of 988 questionnaires were sent by mail to a representative sample of healthy pensioners. Life satisfaction and health status were estimated on two visual analogical scales in answer to the following questions: (1) How would you estimate your state of health? and (2) Are you generally satisfied with your life? The level of physical activity was estimated using a questionnaire which enabled us to calculate: Daily energy expenditure (DEE) [and] VO2 peak. ... Energy spent in activity and VO2 peak estimated from DEE, measured at the age of 65, appear to be strong predictors of well-being 7 years later."
REVERSING B CELL AGING
Tuesday, April 12, 2011
Here are more indications that selective pruning of an aged immune system can restore at least some of its youthful potency. If researchers can understand why the pruning does this, then there is the possibility of skipping the selective destruction and directly manipulating the underlying signaling processes instead: "Age-related alterations in the cellular composition of the B lineage are a major cause of the poor antibody response to vaccination and to infectious agents among the elderly population. The mechanisms leading to these changes are poorly understood. Recently, we have shown that these changes reflect, at least in part, homeostatic pressures imposed by long-lived B cells that accumulate with aging, and that aging in the B lineage can be reversed upon alteration of B cell homeostasis by depletion. Here we discuss homeostatic causes for B lineage immunosenescence, and the potential for its rejuvenation. ... The major conclusion of our study is that age-related alterations in the B lineage are reversible and mediated [by] the long-lived B cells accumulating in the periphery with age ... These observations are the foundations of new paradigms for enhancing immune responsiveness in aging, which may be translated in the future for clinical use. The nature of these homeostatic regulation mechanisms and the cross-talk between peripheral B cells and progenitor cell populations in the [bone marrow] are yet to be identified. This will allow direct manipulation of B cell homeostasis by targeting the regulatory factor(s) rather than by depletion of B cells, to [enhance] immune competence in the elderly."
ALCOR'S LATEST CRYOPRESERVATION
Tuesday, April 12, 2011
The cryonics provider Alcor publishes short summaries of cryopreservation activities, which are educational if you seek to better understand how the process of cryonics unfolds in practice: "In late March of this year, Alcor was notified that a member in Pennsylvania had entered into the hospital with severe abdominal pain and was critically ill. As her medical providers predicted that she would probably not survive, Alcor's Medical Response Director, Aaron Drake and Readiness Coordinator, Steve Graber were on a plane to the east coast within the next three hours. Upon arrival, the member's health condition had stabilized and appeared to have improved somewhat. While optimistic that a recovery might be possible, diagnostic tests and blood labs indicated that a terminal outcome was more probable. This pause in the patient's health decline provided an opportunity to request that Suspended Animation respond as well to help perform a field washout and perfusion. On the third day of the standby, the member succumbed to her illness. Highly cooperative hospital administrators and physicians allowed the Alcor team to perform stabilization and cool down procedures within the patient's private hospital room immediately following pronouncement. The patient was then transferred to a local mortuary where Suspended Animation was set up to complete the next step in the process. The family had pre-paid additional funds to Alcor for a private jet to eliminate the potential delays associated with commercial air travel. After a six and half hour flight, the patient arrived at the Scottsdale Airport, located just a few blocks from Alcor Central. Alcor's surgical team was standing by and performed vitrification procedures throughout the night. On Saturday, March 26th, member A-2478 became Alcor's 104th patient."
LEARNING FROM THE SALAMANDER BRAIN
Monday, April 11, 2011
Salamanders can regenerate more than just limbs: "A study of the salamander brain has led [researchers] to discover a hitherto unknown function of the neurotransmitter dopamine. ... The study was conducted using salamanders which unlike mammals recover fully from a Parkinson's-like condition within a four week period. Parkinson's disease is a neurodegenerative disease characterised by the death of dopamine-producing cells in the mid-brain. As the salamander re-builds all lost dopamine-producing neurons, the researchers examined how the salamander brain detects the absence of these cells. ... What they found out was that the salamander's stem cells are automatically activated when the dopamine concentration drops as a result of the death of dopamine-producing neurons, meaning that the neurotransmitter acts as a constant handbrake on stem cell activity. ... As in mammals, the formation of neurons in the salamander mid-brain is virtually non-existent under normal circumstances. Therefore by studying the salamander, scientists can understand how the production of new nerve cells can be resumed once it has stopped, and how it can be stopped when no more neurons are needed. It is precisely in this regulation that dopamine seems to play a vital part. Many observations also suggest that similar mechanisms are active in other animal species too. Further comparative studies can shed light on how neurotransmitters control stem cells in the brain, knowledge that is of potential use in the development of therapies for neurodegenerative diseases."
ATHEROSCLEROSIS HAPPENS RAPIDLY AND LATE
Monday, April 11, 2011
Many of the characteristic signs and conditions of aging arrive in a rush in later life. The buildup to that point has been going on for a while, but there is a threshold past which matters suddenly accelerate. Here is one example: researchers "have determined the age of atherosclerotic plaques by taking advantage of Carbon-14 (14C) residues in the atmosphere, prevailing after the extensive atomic bomb tests in the 50ties and 60ties. The findings, published in the scientific online journal PLoS ONE, suggest that in most people plaque formation occurs during a relatively short and late time period in life of 3-5 years. ... We suspected that the plaque would be substantially younger than the patients, who were on average were 68 years old at surgery, but we were surprised when we found that the average age of these plaques was less than 10 years. ... If proven true, the growth of atherosclerotic lesions may be interrupted to prevent clinical manifestation, like [stroke], even in late stages of life, at 60 years of age or possibly later. ... The age of plaques was also found to be associated to blood levels of insulin, and plaques with lower age (formed more recently) were found to be more unstable than older plaques and therefore more likely to cause clinical complications." All of which is characteristic of a suddenly runaway process.