Fight Aging! Newsletter, November 21st 2011

November 21st 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!



- An Unusually Clear Example of the Cost of the FDA
- The Methuselah Generation Kickstarter Project
- Longevity Mutations that Only Work With Civilization
- Some Aging Isn't Aging
- Considering the Lab Mice
- Discussion
- Latest Headlines from Fight Aging!


The FDA holds back progress, and makes medical development either expensive or blocks it completely where the costs imposed make it impossible to profitably develop new medical technologies:

"The FDA, like all bureaucratic organizations, long ago came to serve its own continuance above and beyond all other goals. Its own continuance as a political organization depends on releasing as few new medical advances as possible. Approval of medicine that never causes problems gains the bureaucrats no reward, while approval of medicine that does at some point cause problems results in punishment - there is no such thing as an absolutely safe medicine, of course, and the popular media will pillory the FDA for events that are well within the expected range of risk and reward in medicine. A low rate of approval of new technologies causes little harm to the bureaucrats, in comparison, and thus is acceptable for their needs, which is to say a job and a career. Thus the self-interest of those in charge of the FDA at all levels leads to an organization structured to actively sabotage its original goals; this is more or less the place in which all government organizations wind up.

"In any case, here is an example of the cost of the FDA, with some numbers, and a line of research abandoned as being too expensive under the present regulations: Biotechnology firm Geron said last night that it would discontinue its stem-cell research program and halt a pioneering clinical study in people with spinal-cord injury. The decision brings to a halt the world's largest and longest-running program to develop medical treatments from embryonic stem cells, versatile cells able to form many other types of human tissue. ... We're not doing this because we were souring on the field, or as a result of any problems - we have not had any safety issues at all ... The attempt to study stem cells in humans had proved stupendously expensive and slow-moving for Geron. The company estimated that it spent $45 million just to win FDA approval for the initial safety trial of its treatment, known as GRNOPC1. As of October, however, only four patients had been treated, and the company would have had to spend tens of millions more in order to finish the study."


Filmmakers are raising funds to complete their project, a film on longevity science and its future:

"A while back I mentioned the Methuselah Generation, a documentary film on progress on longevity science and the future of the human life span. The more of this sort of media project underway the better, I think - the state of the science really just sells itself once you kick people into waking up and thinking about the topic of aging and rejuvenation biotechnology. The trick is to make this something that people are talking about and thinking about. In any case, the Methuselah Generation filmmakers recently drew my attention to their Kickstarter fundraising page: ... Kickstarter is an all or nothing proposition: either they raise the minimum funding by the set date, $30,000 by December 26th in this case, or none of the funds are released. It's a good system for ensuring a certain minimum level of achievement for a donor's funds - if too little is raised to ensure a good shot at the project then your money is released to be used elsewhere."


Why are there so many simple single gene mutations that significantly extend life and improve health in mice? Why were these not selected by evolution already?

"Deletion of the p66(Shc) gene results in lean and healthy mice, retards aging and protects from aging-associated diseases, raising the question of why p66(Shc) has been selected, and what is its physiological role. We have investigated survival and reproduction of p66(Shc) -/- mice in a population living in a large outdoor enclosure for a year, subjected to food competition and exposed to winter temperatures. Under these conditions deletion of p66(Shc) was strongly counterselected. ... So in other words, lack of p66(Shc) only extends life and causes the mutants to prosper as individuals if they have the benefits of civilization and technology: secure food supplies, secure heating, protection from the elements, and so forth. If shoved out into the uncaring world, they fare poorly - and would soon enough vanish as a genetic line, out-competed by animals with shorter life spans but a better adapted metabolism. We might expect to see similar results for the range of other longevity genes discovered in small mammals: if there was an evolutionary benefit to their selection for animals in the wild, then we should expect that these longevity mutations would already have been selected."


If we think of aging as an accumulation of damage that occurs as a result of the operation of our biology, there are some grey areas:

"We might look on aging as damage that happens as a stochastic, inevitable consequence of the operation of a biochemical system. So the buildup of chemical gunk between your cells is a part of aging, while those times you managed to break bones in your enthusiasm for life are not aging, despite the fact that what's left in the wake of those unfortunate accidents is definitely damage. There are always special cases and grey areas worth thinking about, however. Such as teeth, for example, as I was reminded earlier today. Teeth have a pretty hard time of it, actually, when you stop to think about it. Even in this modern age our teeth maintenance technologies remain woefully inadequate in the face of bacterial species that break down enamel, and so our teeth are one of the most failure-prone and damage-prone parts of the body - and they get to the point of painful dysfunction far earlier than the rest of our organs if left to their own devices.

"But that isn't aging - it's parasitism, no more aging than the consequences of contracting malaria. It's still something we need to fix, of course, and I post on this and related topics because it is of general interest to anyone who follows research into rejuvenation and regeneration. If most or all of us suffer a particular form of bacterial malfeasance that manages to be as damaging as that which chews upon our teeth, than dealing with that problem has to be included in any general toolkit for enhanced human longevity."


An interesting trio of long articles on laboratory mice were recently published, and links can be found in the following Fight Aging! post:

"So very much of the research we watch is conducted in mice, rats, and - increasingly - in naked mole rats and other more esoteric members of the rodent order of mammals. Some of this work is fairly directly applicable to we humans, and some of it is not. For example, the types and proportions of advanced glycation end-product (AGE) that accumulate to damage our cells in later life are very different between rodents and humans, and so early promising work in rats aimed at developing AGE-breaker drugs to wash out these unwanted compounds translated poorly to humans. So how much attention should we give to promising results in mice? That can only be answered for any specific case by knowing more about the use of mice in the laboratory; it is very helpful for the layperson to have a better grasp as to the benefits, limitations, and expectations held by scientists when it comes to research in rodent species that is expected to be applicable to humans. On this note, let me draw your attention to a trio of long articles from Slate that examine the humble laboratory mouse."


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, November 18, 2011
An open access commentary: "Aging is now viewed as a plastic phenotype that can be altered by nutritional, pharmacological and genetic manipulations. However, most pro-longevity mutations are discovered by systematic gene deletion or RNA interference screens, which mainly reveal abolished or diminished gene functions. In our recent publications, we used global acetylation proteome screens to study aging in yeast, and showed that enhancing the function of certain genes through specific acetylation can promote longevity. ... It is well known that acetylation of histone proteins in cultured human fibroblasts decreases during aging, which is believed to be directly related to decreased metabolic rate and reproductive capacity associated with aging. However, histone deacetylation is not likely to be a universal driving force of aging because histone acetylation and deacetylation mimetics similarly shortened life span, which could simply reflect nonspecific fitness decreases in both instances. Extension of lifespan promoted by certain genetic and/or pharmacological perturbations will more likely lead to identification of bona fide regulatory factors of aging. ... Aging is conventionally thought to be characterized by accumulation of molecular, cellular, and organ damage, leading to increased vulnerability to disease and death. Our data, on the contrary, support the idea that the gradual loss of a crucial component promoting 'healthy young status' might underlie an intrinsic aging process. Many of the mutations that extend life span decrease the activity of external nutrient signaling, such as the IGF (insulin-like growth factor)/insulin and the TOR (target of rapamycin) pathways, suggesting that they may induce a metabolic state similar to that resulting from periods of food shortage."

Friday, November 18, 2011
If you can build new living tissue to be implanted in patients, then why not also give it the capacity to perform additional useful tasks? This is a technology platform with some potential: "combining gene therapy with tissue engineering could avoid the need for frequent injections of recombinant drugs. Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers [have demonstrated] the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. ... Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. ... The paradigm shift here is, 'why don't we instruct your own cells to be the factory?' ... [Researchers] provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO). ... The researchers created the drug-secreting vessels by isolating endothelial colony-forming cells from human blood and inserting a gene instructing the cells to produce EPO. They then added mesenchymal stem cells, suspended the cells in a gel, and injected this mixture into the mice, just under the skin. The cells spontaneously formed networks of blood vessels, lined with the engineered endothelial cells. Within a week, the vessels hooked up with the animals' own vessels, releasing EPO into the bloodstream. Tests showed that the drug circulated throughout the body and reversed anemia in the mice."

Thursday, November 17, 2011
From h+ Magazine: "As serious life extension appears on an ever nearer horizon simultaneous with a period of social and economic rebellion and an increasing sense of global chaos, this may be a good time to entertain these anxieties while thinking beyond the two extant competing simplistic arguments. The current conflicting views seem to be these: A: Hyperlongevity will be for rich people only and we can't afford to add to the population vs. B: Technologies get distributed to more and more people at an increasing rate of speed through the auspices of the free market. Demand increases. Production increases. The price gets lower. Demand increases. Production increases. The price gets lower... ad infinitum. In fact, the wealthy who are the early adopters of a new technology get to spend a lot of money on crappy versions of new technologies that are not ready for prime time. At the risk of being obvious, it seems like there's a lot of room in the middle for more nuanced, less certain views. ... Very few people would say that we shouldn't cure cancer or heart disease because only the wealthy will be able to afford it - and those who did would be seen by most as anti-human and/or insufferably whiny. Seen in this light, it becomes obvious that this whole 'only the rich will get hyperlongevity' mentality is pathetic in the extreme - a concession of defeat before the outset. If you think optimal health and longevity should be distributed, you won't say, 'Well, it won't be distributed so I'm against it.' You will try to make sure it gets distributed. Whether you believe in medical care for all through government or pushing these solutions towards a very large mass market or creating an open source culture that takes production and distribution into its own decentralized hands, you'll work or fight for one or several (or all) of these solutions."

Thursday, November 17, 2011
Teeth are one of the first parts of our body to become seriously damaged as the years go by, thanks to bacterial agents, but that will soon enough be a thing of the past. On the one hand enamel regeneration is close to realization, and on the other hand so are ways of eliminating the agents of tooth decay: "A new mouthwash developed by a microbiologist at the UCLA School of Dentistry is highly successful in targeting the harmful Streptococcus mutans bacteria that is the principal cause tooth decay and cavities. In a recent clinical study, 12 subjects who rinsed just one time with the experimental mouthwash experienced a nearly complete elimination of the S. mutans bacteria over the entire four-day testing period. ... This new mouthwash is the product of nearly a decade of research conducted by Wenyuan Shi ... Shi developed a new antimicrobial technology called STAMP (specifically targeted anti-microbial peptides) [which] acts as a sort of 'smart bomb,' eliminating only the harmful bacteria and remaining effective for an extended period. ... With this new antimicrobial technology, we have the prospect of actually wiping out tooth decay in our lifetime."

Wednesday, November 16, 2011
As knowledge of cellular programming and signaling systems increases, the future of cell therapies will most likely move away from transplants and towards controlling existing populations of cells in the body: "In order to regenerate damaged heart muscle as caused by a heart attack [simpler] vertebrates like the salamander adopt a strategy whereby surviving healthy heart muscle cells regress into an embryonic state. This process, which is known as dedifferentiation, produces cells which contain a series of stem cell markers and re-attain their cell division activity. Thus, new cells are produced which convert, in turn, into heart muscle cells. The cardiac function is then restored through the remodelling of the muscle tissue. An optimised repair mechanism of this kind does not exist in humans. Although heart stem cells were discovered some time ago, exactly how and to what extent they play a role in cardiac repair is a matter of dispute. It has only been known for a few years that processes comparable to those found in the salamander even exist in mammals. ... [Researchers have] now discovered the molecule responsible for controlling this dedifferentiation of heart muscle cells in mammals. The scientists initially noticed the high concentration of oncostatin M in tissue samples from the hearts of patients suffering from myocardial infarction. It was already known that this protein is responsible for the dedifferentiation of different cell types, among other things. ... Using a mouse infarct model, the [researchers] succeeded in demonstrating that oncostatin M actually does stimulate the repair of damaged heart muscle tissue as presumed. One of the two test groups had been modified genetically in advance to ensure that the oncostatin M could not have any effect in these animals. ... The difference between the two groups was astonishing. Whereas in the group in which oncostatin M could take effect almost all animals were still alive after four weeks, 40 percent of the genetically modified mice had died from the effects of the infarction."

Wednesday, November 16, 2011
Here is an interesting application of cell therapy, which demonstrates the point that an artificial replacement for an organ doesn't necessarily have to replicate the form and structure of that organ: "Eight-month-old Iyaad Syed now looks the picture of health - but six months ago he was close to death. A virus had damaged his liver causing it to fail. Instead of going on a waiting list for a transplant, doctors injected donor liver cells into his abdomen. These processed toxins and produced vital proteins - acting rather like a temporary liver. The cells were coated with a chemical found in algae which prevented them from being attacked by the immune system. After two weeks his own liver had begun to recover. ... The question now is whether the technique could be used to benefit other patients with acute liver failure. The team [is] urging caution - a large clinical trial is needed to test the effectiveness of the technique. ... The principle of this new technique is certainly ground-breaking and we would welcome the results of further clinical trials to see if it could become a standard treatment for both adults and children."

Tuesday, November 15, 2011
Autophagy is a collection of similar processes for cellular housekeeping: recycling broken components so that they can't cause harm. More autophagy means a better running biological machine, and that in turn brings enhanced longevity. Aging, after all, is really nothing more than the accumulation of unrepaired biological damage. Here is another example of this principle in action: "Evidence for a regulatory role of the miR-34 family in senescence is growing. However, the exact role of miR-34 in aging in vivo remains unclear. Here, we report that a mir-34 loss-of-function mutation in Caenorhabditis elegans markedly delays the age-related physiological decline, extends lifespan, and increases resistance to heat and oxidative stress. We also found that RNAi against [autophagy-related genes] significantly reversed the lifespan-extending effect of the mir-34 mutants. Furthermore, miR-34a inhibits [gene expression of an autophagy-related gene] at the post-transcriptional level in vitro ... Our results demonstrate that the C. elegans mir-34 [loss of function] mutation extends lifespan by enhancing autophagic flux in C. elegans, and that miR-34 represses autophagy by directly inhibiting the [expression of autophagy-related genes] in mammalian cells."

Tuesday, November 15, 2011
More evidence for the utility of early stage stem cell therapies of the sort that have been available overseas through medical tourism for a number of years, and which would also be available in the US if not for the FDA: "16 patients with severe heart failure received a purified batch of cardiac stem cells. Within a year, their heart function markedly improved. The heart's pumping ability can be quantified through the "Left Ventricle Ejection Fraction," a measure of how much blood the heart pumps with each contraction. A patient with an LVEF of less than 40% is considered to suffer severe heart failure. When the study began, Bolli's patients had an average LVEF of 30.3%. Four months after receiving stem cells, it was 38.5%. Among seven patients who were followed for a full year, it improved to an astounding 42.5%. A control group of seven patients, given nothing but standard maintenance medications, showed no improvement at all. ... We were surprised by the magnitude of improvement. ... [Elsewhere] 17 patients [were] given stem cells approximately six weeks after suffering a moderate to major heart attack. All had lost enough tissue to put them 'at big risk' of future heart failure ... The results were striking. Not only did scar tissue retreat - shrinking [between] 30% and 47% - [but] the patients actually generated new heart tissue. On average, the stem cell recipients grew the equivalent of 600 million new heart cells .... By way of perspective, a major heart attack might kill off a billion cells. ... the heart contains a type of stem cell that can develop into either heart muscle or blood vessel components - in essence, whatever the heart requires at a particular point in time. The problem for patients [is] that there simply aren't enough of these repair cells waiting around. The experimental treatments involve removing stem cells through a biopsy, and making millions of copies in a laboratory."

Monday, November 14, 2011
The Parkinson's research community may turn out to be an ally in efforts to develop mitochondrial repair technologies suitable for use in rejuvenation: "genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. ... Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too ... Normally, when mitochondria go bad, PINK1 tags Miro, [a protein which literally hitches a molecular motor onto the organelle], to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion. The organelle, unable to move, can then be disposed of: The cell literally digests it. But when either PINK1 or Parkin is mutated, this containment system fails, leaving the damaged mitochondria free to move about the cell, spewing toxic compounds and fusing to otherwise healthy mitochondria and introducing damaged components. ... The study's findings are consistent with observed changes in mitochondrial distribution, transport and dynamics in other neurodegenerative diseases ... Whether it's clearing out damaged mitochondria, or preventing mitochondrial damage, the common thread is that there's too much damage in mitochondria in a particular brain region. ... [Researchers are] interested in the possibility of helping neurons flush out bad mitochondria or make enough new, healthy mitochondria to keep them viable."

Monday, November 14, 2011
The latest Cryonics issue is out: "The 2011 4th quarter issue of Cryonics magazine is dedicated to the 'father of cryonics,' Robert Ettinger, who was cryopreserved on July 23, 2011. Alcor staff member Mike Perry contributes an historical piece on Ettinger and Mark Plus and Charles Platt write about his influence on contemporary cryonics, futurism, and the cryobiology community. Cryonics editor Aschwin de Wolf compiled Robert Ettinger's mature thoughts on the feasibility of 'mind uploading' and situates his outlook in a broader philosophical context. This issue also features a detailed article by the Alcor Board of Directors and Management about member underfunding and its associated challenges for Alcor's long-term financial health. Alcor member, and prolific science fiction writer, Gregory Benford is featured in this issue's member profile."



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