FIGHT AGING! NEWSLETTER
June 4th 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!
- An Update on the Longecity Crowdfunded Microglia Study
- Video of Aubrey de Grey at TEDxUChicago
- Civilization as a Side-Effect of the Urge to Immortality
- Does Medicine For Aging Exist?
- Latest Headlines from Fight Aging!
AN UPDATE ON THE LONGECITY CROWDFUNDED MICROGLIA STUDY
Last year the Longecity community completed fundraising for a study of microglia transplants as a means to reverse some aspects of neurodegeneration. Here is an update on how that is going:
"Cognitive functions of the brain decline with age. One of the protective cell types in the brain are called microglia cells. However, these microglia cells also loose function with age. Our aim is to replace non-functional microglia with new and young microglia cells derived from adult stem cells. We will inject these young microglia cells into 'Alzheimer mice' - a model for Alzheimers disease. After giving the cells some time to work, we will sacrifice the mice and measure microglia activity, neurogenesis, proliferation of neuroprogenitors and plaque density in the brain. A reduction in plaque density of Alzheimer mice would be a first proof that the transplanted microglia are performing their expected function.
"To visualize microglia and amyloid plaques in vivo, we established different staining protocols (including histology and immunohistology) to later evaluate microglia number after transplantation and also amyloid load. ... Most of our measurements will take place in the hippocampus, one of the brain regions where many of the degenerative changes happen in Alzheimer's disease. ... In summary we have established all necessary methods for brain staining, tested the sterology method using non-transplanted mice and are now ready to transplant. We finally got the approval from our animal guys after waiting for 10 month (they are a bit over-correct here in Germany).
"One thing to note about animal studies, and medical research in general, is the exceedingly heavy layer of regulation that exists in much of the world. There are boards and reviews and an endless procession of paperwork, all apparently devoted to slowing things down. It really can take the better part of a year to obtain institutional approval to perform a comparatively simple study - and it is usually impossible to have that approval timed to allow research to proceed without delay. Another thing to note is that even the comparatively simple work in the life sciences involves many, many details of measurement, cell cultures, and other line items. Much of that is largely hidden from the outside world and glossed over in the popular science press, which prefers to focus on the end results or new achievements rather than all of the well known but time-consuming foundation work that goes into any study."
VIDEO OF AUBREY DE GREY AT TEDXUCHICAGO
TEDxUChicago 2012 was held a little while back, and here is video of SENS Foundation cofounder Aubrey de Grey presenting at the event:
CIVILIZATION AS A SIDE-EFFECT OF THE URGE TO IMMORTALITY
Here is an interesting view of the deep cultural roots of the urge to live longer:
"Cave's fascinating new book, Immortality, posits that civilization is a major side effect of humanity's attempts to live forever. He argues that our sophisticated minds inexorably recognize that, like all other living things, we will one day die. Simultaneously, Cave asserts, 'The one thing that these minds cannot imagine is that very state of nonexistence; it is literally inconceivable. Death therefore presents itself as both inevitable and impossible. This is what I will call the Mortality Paradox, and its resolution is what gives shape to the immortality narratives, and therefore to civilization.' ... Cave identifies four immortality narratives that drive civilizations over time which he calls; (1) Staying Alive, (2) Resurrection, (3) Soul, and (4) Legacy. Cave gracefully marches through his four immortality narratives citing examples from history, psychology, and religion up to the modern day. 'At its core, a civilization is a collection of life extension technologies: agriculture to ensure food in steady supply, clothing to stave off cold, architecture to provide shelter and safety, better weapons for hunting and defense, and medicine to combat injury and disease,' he writes."
"I think that it is useful to realize that much of our present culture - and that includes the culture of longevity science and its supporters - has very ancient roots indeed. Unbroken lines can be traced from the incentives and psychology of stone age shamans through to the magical thinking and oral fixations of today. Little but technology separates us from our ancestors of five or ten thousand years past, and what to what use do we put that technology? We use it to make our greatest myths real: we are building the world that our ancestors chose to imagine, and which we too imagine, driven by our shared human condition and neural physiology.
"Spend a little time with ancient myth, and you'll soon see there is little fundamental difference between the tales of thousands of years past and the folktales of a few hundred years ago. Our present popular entertainments merely continue the theme, a thousand more frills but the same underlying psychology at work. We humans identify with a certain set of stories, and those stories are found repeated throughout our mythologies. In turn, mythology drives technology, as technology is, at heart, a way to satisfy human desires.
"As to those parts of mythology that we haven't got to yet - such as unbounded longevity, enabled through biotechnology - well, give it time. We have managed flight, standing atop mountains, journeying to the moon, transmuting the elements, growing food in abundance beyond the wildest dreams of past centuries, changing the course of floods and rivers, and far more. Even the oldest myths will in due course be reconstructed in the real world, even if that means we will build cities in the clouds, cats that can talk, and spirits for companionship. Given sufficiently advanced biotechnology and an understanding of the fundaments of intelligence, the world of a century from now will be populated by people who do not age and disembodied machine intelligences - easily enough matched to the roles of hidden peoples and household spirits in legend."
DOES MEDICINE FOR AGING EXIST?
The short answer: arguably yes, but it's generally awful and ineffective in the grand scheme of things. We should look to the future of biotechnologies that can repair cellular damage rather than chase our tails in excitement over present drugs that might incrementally slow aging:
"Asking and attempting to answer questions like 'does medicine for aging exist' is going to make you unpopular in some quarters no matter how you answer. The large and energetic 'anti-aging' marketplace, eternally plagued by the dishonesty of its bad apples, has been crying 'yes, yes, get your treatments for aging here' for about as long as mankind has existed. The invention of fraud no doubt followed the discovery of the concepts of value and trade by only a few heartbeats. When no-one could in fact do much of anything about aging, one might say 'so what?' Fraud and lies about extending life were no different then than fraud and lies about anything else that didn't exist and couldn't be made to exist - such as the ownership rights to certain bridges, for example.
"In these later days of science and reason, however, in which we stand upon the verge of building real and meaningful ways to treat aging, that commercial 'anti-aging' market is a millstone around the necks of the scientific community. It is in fact a large part of the reason why up until very recently the aging research field was extremely hostile towards anyone talking seriously about treating aging. So you are going to see care taken when people in the scientific community speak on such topics. For my part, I think it's completely fair to put forward that, by modern standards of drug development, you could point to rapamycin and metformin and say 'these are candidate treatments for aging.' By this I mean that they are likely to produce minimal benefits, have potentially ugly side-effects, and are not yet really tested for that specific usage in humans - which describes both a fair chunk of the drug discovery pipeline and many drugs out there in widespread use. We are willing to call those therapies for the conditions they are used to treat.
"But let's be clear: as prospective therapies for aging, these drugs are terrible. Truly bad. They are far worse than exercise or calorie restriction - they produce lesser benefits and you get unpleasant side-effects into the bargain. So given all of that I don't think it is unreasonable to say that yes, treatments for aging exist at the present time, and they are awful.
"(It is worth pointing out that a gain in life span of 20% in mice is not all that in the grand scheme of things. Exercise can do better, and calorie restriction does twice as well. Further, it is not seriously expected that any gain of 20% in life span in mice through metabolic alteration will translate to a similarly meaningful gain in human life span - which has to do with many of the differences that cause us to be long-lived already for our size. For example, calorie restriction is not thought to be capable of producing more than a few years of gain in maximal human life span, even while it produces large gains in health and resistance to age-related disease).
"The real path to the future, to my eyes, is to skip over all of this longevity-enhancing drug discovery nonsense, interesting though it may be, and focus on repair of specific forms of cellular and molecular damage - such as the detailed methodologies proposed in the SENS vision. If SENS or similar programs for research and development fail to become a dominant approach to longevity science, and the foreseeable future thus remains a heaping helping of more longevity-enhancing drug discovery nonsense, then therapies for aging will continue to be generally awful."
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!
CREATING PARTIAL REGENERATION IN THE SPINE
Friday, June 1, 2012
Researchers make paralyzed rats walk through a mix of chemical stimulation and structured physical therapy; only a little regrowth in the spine occurs, but the lower spinal column can take over some of the lost functionality under the right circumstances: "a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened. ... After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated. ... until now the spinal cord expressed so little plasticity after severe injury that recovery was impossible. ... under certain conditions, plasticity and recovery can take place in these severe cases - but only if the dormant spinal column is first woken up. To do this, [researchers] injected a chemical solution of monoamine agonists into the rats. These chemicals trigger cell responses by binding to specific dopamine, adrenaline, and serotonin receptors located on the spinal neurons. This cocktail replaces neurotransmitters released by brainstem pathways in healthy subjects and acts to excite neurons and ready them to coordinate lower body movement when the time is right. ... Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. ... a stimulated rat spinal column - physically isolated from the brain from the lesion down - developed in a surprising way: It started taking over the task of modulating leg movement, allowing previously paralyzed animals to walk over treadmills. These experiments revealed that the movement of the treadmill created sensory feedback that initiated walking - the innate intelligence of the spinal column took over, and walking essentially occurred without any input from the rat's actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own volition. ... newly formed fibers bypassed the original spinal lesion and allowed signals from the brain to reach the electrochemically-awakened spine. And the signal was sufficiently strong to initiate movement over ground."
ON THE LEGAL STATUS OF CRYOPRESERVED PEOPLE
Friday, June 1, 2012
There is death and then there is information theoretic death - a person who is cryopreserved is a good deal less dead than someone who went to the grave. The fine structure and data of the mind still exist, in a cold-stored stasis, and thus might be restored through foreseeable future technology. Here are some notes on the legal situation with respect to cryopreserved people: "This article series seeks to compare the legal protection of cryonics patients under their present legal status to the legal protection which would be afforded them if they were recognized as persons under the law, thinking ahead to such future time as it becomes reasonably possible to put legal and political pressure towards enhanced legal recognition of cryonics patients. The previous article examined laws that directly affect what happens to a person's body after legal death, both in the period immediately after declaration of legal death, and indefinitely thereafter. We saw that the amount of prospective autonomy a person is permitted in this regard can vary significantly from jurisdiction to jurisdiction, with more or less consideration afforded to the wishes of the person's next of kin, religious beliefs, societal norms and other public interests. Two other legal structures which can and are used by cryonicists to promote the success and timeliness of cryopreservation, maintenance, and resuscitation are wills and trusts."
WORK ON RESTORING FUNCTION IN HUNTINGTON'S DISEASE
Thursday, May 31, 2012
Researchers "have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models. ... Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory. In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD. ... the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed. ... transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD."
EFFECTS OF EXERCISE AND DIET ON MORTALITY IN THE OLD
Thursday, May 31, 2012
Via EurekAlert!: researchers "studied 713 women aged 70 to 79 years who took part in the Women's Health and Aging Studies. This study was designed to evaluate the causes and course of physical disability in older women living in the community. ... A number of studies have measured the positive impact of exercise and healthy eating on life expectancy, but what makes this study unique is that we looked at these two factors together. ... Researchers found that the women who were most physically active and had the highest fruit and vegetable consumption were eight times more likely to survive the five-year follow-up period than the women with the lowest rates. ... Study participants' physical activity was measured through a questionnaire that asked the amount of time the spent doing various levels of physical activity, which was then converted to the number of calories expended. The women were then followed up to establish the links between healthy eating, exercise and survival rates. Key research findings included: More than half of the 713 participants (53%) didn't do any exercise, 21% were moderately active, and the remaining 26% were in the most active group at the study's outset. During the five-year follow up, 11.5% of the participants died. Serum carotenoid levels were 12% higher in the women who survived and total physical activity was more than twice as high. Women in the most active group at baseline had a 71% lower five-year death rate than the women in the least active group. Women in the highest carotenoid group at baseline had a 46% lower five-year death rate than the women in the lowest carotenoid group. When taken together, physical activity levels and total serum carotenoids predicted better survival."
A HIGH LEVEL VIEW OF WHAT IS KNOWN OF AGING
Wednesday, May 30, 2012
The Guardian talks to researcher Tom Kirkwood: "We've known for some time that ageing is extremely variable; that everybody is different and that the differences of individuals' experience of ageing are greater than differences in earlier stages of life ... And why so variable? ... Because of the nature of the ageing process. I've been involved in this field for more than 35 years and when I entered it people fondly believed that ageing was programmed; that there was a mechanism inside our bodies that determined how long we would live. It was kind of written into our genes that we would die at a certain age. What we've been able to show is that the idea of this genetically programmed ageing makes no sense at all. There is no evidence. ... But, surely, genetic influences - a family susceptibility to cardiovascular problems, for instance - play a part in determining longevity? Only to a degree. [For example] a Danish study shows that such influences only explain about a quarter of the factors determining a lifespan. ... What we now know is that the genetic factors that influence your longevity are not genes that measure out the passage of time; the reason we age and die is because, as we live our lives, our bodies accumululate a great variety of small faults in the cells, and the molecules that make up the cells in our body - so ageing is driven by this accumulation of faults. The genes that influence longevity are those that influence how well the body copes with damage, how aggressive our repair mechanisms are; they're genes that regulate the house-keeping and maintenance and repair." All the more reason to focus research on the development of biotechnologies that can do a far better job of repair.
FIBROBLAST GROWTH FACTOR AND ZEBRAFISH REGENERATION
Wednesday, May 30, 2012
Small steps towards understanding the greater regenerative capacity of one species: "When the spinal cord is severed in humans and other mammals, the immune system kicks in, activating specialised cells called glia to prevent bleeding into it. ... Glia are the workmen of the nervous system. The glia proliferate, forming bigger cells that span the wound site in order to prevent bleeding into it. They come in and try to sort out problems. A glial scar forms. ... However, the scar prevents axons, threadlike structures of nerve cells that carry impulses to the brain, of neighbouring nerve cells from penetrating the wound. The result is paralysis. ... The axons upstream and downstream of the lesion sites are never able to penetrate the glial scar to reform. This is a major barrier in mammalian spinal cord regeneration. In contrast, the zebra fish glia form a bridge that spans the injury site but allow the penetration of axons into it. The fish can fully regenerate its spinal cord within two months of injury. ... Scientists discovered the protein, called fibroblast growth factor (fgf), controlled the shape of the glia, and accounted for the difference in the response to spinal cord injury between humans and zebra fish. The scientists showed the protein could be manipulated in the zebra fish to speed up tissue repair even more. ... The hope is that fgf could eventually be used to promote better results in spinal cord repair in people."
TISSUE ENGINEERING OF SMALL BLOOD VESSELS
Tuesday, May 29, 2012
Researchers are increasingly able to produce networks of small blood vessels - here in a way that is only immediately applicable to testing, but which will no doubt lead to further progress: "bioengineers have developed the first structure to grow small human blood vessels, creating a 3-D test bed that offers a better way to study disease, test drugs and perhaps someday grow human tissues for transplant. ... with this, we can really dissect what happens at the interface between the blood and the tissue. We can start to look at how these diseases start to progress and develop efficient therapies. ... [Researchers] first built the structure out of the body's most abundant protein, collagen, [created] tiny channels and injected this honeycomb with human endothelial cells, which line human blood vessels. During a period of two weeks, the endothelial cells grew throughout the structure and formed tubes through the mold's rectangular channels, just as they do in the human body. When brain cells were injected into the surrounding gel, the cells released chemicals that prompted the engineered vessels to sprout new branches, extending the network. A similar system could supply blood to engineered tissue before transplant into the body. ... The engineered vessels could transport human blood smoothly, even around corners. And when treated with an inflammatory compound the vessels developed clots, similar to what real vessels do when they become inflamed. The system also shows promise as a model for tumor progression. Cancer begins as a hard tumor but secretes chemicals that cause nearby vessels to bulge and then sprout. Eventually tumor cells use these blood vessels to penetrate the bloodstream and colonize new parts of the body. When the researchers added to their system a signaling protein for vessel growth that's overabundant in cancer and other diseases, new blood vessels sprouted from the originals. These new vessels were leaky, just as they are in human cancers. ... With this system we can dissect out each component or we can put them together to look at a complex problem. That's a nice thing - we can isolate the biophysical, biochemical or cellular components. How do endothelial cells respond to blood flow or to different chemicals, how do the endothelial cells interact with their surroundings, and how do these interactions affect the vessels' barrier function?"
A CHEAP AND ABUNDANT SOURCE OF HEART MUSCLE CELLS
Tuesday, May 29, 2012
Researchers find a low-cost way of creating cardiomyocytes on demand: they can "transform human stem cells - both embryonic and induced pluripotent stem cells - into the critical heart muscle cells by simple manipulation of one key developmental pathway. ... manipulating a major signaling pathway known as Wnt - turning it on and off at prescribed points in time using just two off-the-shelf small molecule chemicals - is enough to efficiently direct stem cell differentiation to cardiomyocytes. ... The technique promises a uniform, inexpensive and far more efficient alternative to the complex bath of serum or growth factors now used to nudge blank slate stem cells to become specialized heart cells. ... Our protocol is more efficient and robust. We have been able to reliably generate greater than 80 percent cardiomyocytes in the final population while other methods produce about 30 percent cardiomyocytes with high batch-to-batch variability. ... The ability to make the key heart cells in abundance and in a precisely defined way is important because it shows the potential to make the production of large, uniform batches of cardiomyocytes routine. [The] cells are in great demand for research, and increasingly for the high throughput screens used by the pharmaceutical industry to test drugs and potential drugs for toxic effects. ... Scientists also have high hopes that one day healthy lab-grown heart cells can be used to replace the cardiomyocytes that die as a result of heart disease. ... Many forms of heart disease are due to the loss or death of functioning cardiomyocytes, so strategies to replace heart cells in the diseased heart continue to be of interest. For example, in a large heart attack up to 1 billion cardiomyocytes die. The heart has a limited ability to repair itself, so being able to supply large numbers of potentially patient-matched cardiomyocytes could help."
AUTOANTIBODIES IN ALZHEIMER'S DISEASE
Monday, May 28, 2012
Via ScienceDaily, an example of a more recent form of theory to explain the development of Alzheimer's disease: "dying or damaged brain cells release debris into the bloodstream and give rise to specific autoantibodies that appear to be reliable biomarkers for early diagnosis of Alzheimer's and other neurodegenerative diseases. The researchers also identify a key mechanism in the development of Alzheimer's that mirrors a process that is common in such autoimmune disorders as rheumatoid arthritis. ... human blood contains perhaps thousands of autoantibodies for clearing cellular debris, and that some of these autoantibodies can potentially be used to accurately diagnose neurodegenerative diseases ... The researchers focused on the role of enzymes, called PADs, in citrullination, a process that converts one type of amino acid into another (amino acids are the building blocks of proteins). After examining postmortem human brain tissue from individuals with Alzheimer's disease and healthy controls, the researchers found that neurons located in the area of the brain first affected by Alzheimer's disease accumulate both citrullinated proteins and a PAD enzyme. ... Their results suggest that when neuron cells die, they release their contents into the fluid that surrounds the brain. The cellular remains then enter the bloodstream and their presence generates the production of specific autoantibodies that target this neuronal debris. ... Our previous studies provided evidence that some of these autoantibodies may be able to return to the brain through breaches in the blood-brain barrier. Once there, they selectively bind to the surfaces of neurons, disrupting the function of the brain cells and accelerating the accumulation of beta amyloid deposits. This chronic cycle of protein-debris-generating autoantibodies that can then seep through the blood-brain barrier helps explain the long-term, progressive degeneration that results from Alzheimer's disease."
THOUGHTS ON THE DE GREY/BLAKEMORE DEBATE ON LONGEVITY SCIENCE
Monday, May 28, 2012
Filmmaker Robert Pappas, who produced To Age or Not to Age, here offers some thoughts on the recent academic debate between Aubrey de Grey and Colin Blakemore: "The debate's title was: 'Resolved this house wants to defeat aging entirely' and was to cover the feasibility and desirability of bringing aging under medical control. After watching the video of the debate; among other things, it strikes me that the title itself helps obscure the nature and process of the scientific research currently underway to extend healthspan, and by implication, lifespan. The problem waxes ironic. To a large degree, Aubrey became 'famous' by uttering the following on camera: 'I'm claiming that the first person to live to a 1,000, subject of course to global catastrophes, is actually, probably only about 10 years younger than the 1st 150 year old, and that's quite a thought.' On the one hand, Aubrey's thesis is provocative and possibly true - but there is a downside to such a framing of the discussion. The viewer or reader reacts - 'What, 10 years after 150, what? A 1,000 years, people from the middle ages would be alive, what? Population, resources? Bombs? - Who wants to live that long, the world sucks now, ahhhhhhh....!' I personally observed similar reactions in a portion of the audience who watched my film." This is a framing of the standard debate in advocacy for any bold new step forward in science: do you plant a flag right out there to set the bounds of the debate, or do you take the softly-softly incremental approach? In this age of pervasive death cult environmentalism, to the point at which the average man in the street thinks - falsely - that living longer will in some way cause catastrophe, I'm in favor of the former approach lest the middle position in the debate become suppression of research and development in medicine.