FIGHT AGING! NEWSLETTER
March 12th 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!
- Pondering the State of 2020
- Signs of Progress in Crowdsourced Science Funding
- Enabling a Middle Path for Organ Transplants
- A Symposium on Cryonics and Neurodegenerative Disease
- Latest Headlines from Fight Aging!
PONDERING THE STATE OF 2020
Predicting the future is a fool's game, and never more so than for the near future - just a few years ahead. But the process of trying can be educational, and leads us to consider at least what might be plausible:
"Short term predictions for the future, such as looking at the next ten years, are especially challenging; the random nature of life and circumstance tends to dominate on that timescale, which means the trends that can be picked up from various 30-60 year time frames are not so helpful as guidelines for progress. One good day or one bad day for a developer or fundraiser somewhere in the world can can spiral outward to move a due date for new technology a few years in either direction, but that sort of stochastic noise evens out over longer periods of time.
"I've pondered the late 2030s to early 2040s in past years - which are still enough business cycles removed from here and now to expect a certain evening out of the uncertainties of progress. But what about the next round number between here and there: 2020? That is a more challenging and uncertain prospect, but here are some thoughts."
SIGNS OF PROGRESS IN CROWDSOURCED SCIENCE FUNDING
The future of life science research projects costing less than a few hundred thousand dollars is crowdfunding: a very transparent process of gathering supporters, talking about the work, and raising funds from many people who come together online to donate and watch the work as it progresses. This will develop in parallel with the open biotech communities, where amateurs work alongside professionals to move the frontiers of science. So it is worth watching how the first marketplaces develop:
"If you've been reading Fight Aging! for a while, you'll recall that I've discussed organized crowdsourcing of funding of life science research - and longevity science in particular - for a few years now. This is a concept whose time has come: the Internet is providing great transparency and insight into all fields of endeavor, the cost of biotechnology has fallen rapidly to the point at which graduate students and a few tens of thousands of dollars can accomplish meaningful novel research, and crowdsourcing is achieving critical mass in other markets.
"So we have ventures like Kickstarter, which is making a name for itself in art, publishing, and manufacturing projects. That is an example of a successful marketplace, where workers and funders can come together to raise sums comparable to pre-angel investments in start up companies - but on their own terms, and usually far better terms.
"If you can raise money for books, art projects, and widgets, why not for discrete life science research projects with determined goals? The LongeCity (previously the Immortality Institute) crowd have been trying this for some years, with a great deal of success considering the limited audience of this community in comparison to the audience available through Kickstarter. It is sad but true that far more people are brought to a state of excitedly opening their wallets for the development of an iPhone widget than for any sort of biotechnology project, even one that will contribute to the reversal of aging.
"But regardless, the groundwork is laid - this is the time for growth in crowdsourced funding. For the scientific community, the remaining piece of the puzzle at this time would seem to be a viable first marketplace, some Kickstarter-for-science that captures an audience and replicates the success of Kickstarter in this field. Once that is done a single time, then the idea will be accepted by the public and many such ventures can blossom."
A new venture funded Kickstarter-for-science called Petridish launched recently, and seems worth keeping an eye on:
ENABLING A MIDDLE PATH FOR ORGAN TRANSPLANTS
It's a crowded time for development of organ transplant and regrowth methodologies - which is all the better for us:
The near future of organ transplants will become very varied, as a range of different viable types of technology are presently undergoing active development. A short list looks much like this: 1) Incremental progress in old-style organ transplants, such as improving the donation system, allowing organs to be stored outside the body for longer periods of time, and so forth. 2) Decellularization, in which a donor organ is stripped of cells, leaving only the scaffold of the extracellular matrix. The scaffold is repopulated from the patient's cells, removing the possibility of immune rejection and need for immunosuppressant drugs. 3) Electromechanical and bioartificial organs, including hearts, lungs, and kidneys, continue to improve at a good pace. New types of small artificial organ are becoming possible thanks to advances in materials science. 4) Creating organ tissue and scaffolds from scratch through a variety of methods, such as the 3-D printing pioneered by a number of groups. 5) Xenotransplantation, the use of animal organs for human patients, is also becoming more viable as a near-term prospect. 6) Lastly, there are the researchers who aim to rebuild damaged organs in situ through manipulation of stem cells and signaling processes in normal regeneration.
"There will be a great deal of innovation and healthy competition over the next two decades before this larger cycle of technological progress in medicine settles down to a few mature and tried and tested ways of fixing broken and age-damaged organs in the body. To add to the list of strategies, I noticed an article today on a possible middle path between old-style donor transplants (immunosuppressant drugs and all) and the near future of organs that are populated by the patient's own stem cells. It may be possible to use the knowledge acquired by stem cell researchers to date in order to minimize or completely remove the risk of immune rejection in a traditional transplant of a donor organ."
The process outlined is a fascinating one that involves engineering a person to become chimeric, by transplanting not only an organ but also part of the donor's immune system, such that the patient has, effectively, two distinct immune systems working together.
A SYMPOSIUM ON CRYONICS AND NEURODEGENERATIVE DISEASE
News of an upcoming event on July 7th in Portland, Oregon:
"Conventional wisdom in life extension circles is that making cryonics arrangements allows one to benefit from rejuvenation technologies that are not available during one's existing lifespan. Aside from the risk of high-impact accidents or getting lost at sea, there is one challenge that some cryonicists will face when they grow older; the debilitating consequences of brain-threatening disorders. One of the unfortunate effects of the increase in human lifespan is a corresponding increase in late-onset identity-destroying brain disorders. We know that some patients at the existing cryonics organizations were cryopreserved after advanced Alzheimer's disease. Some cryonics organization members who developed Alzheimer's disease were not preserved at all, due to lapsed insurance and/or cryopreservation arrangements.
"The main challenges and risks associated with low-temperature preservation of the brain after death relate to (a) overbearing regulation that prevents sensible end of life decisions and increases risk of a poor preservation, and (b) your removal from the scene as a willful actor, capable of defending your own interests. Neurodegenerative conditions like Alzheimer's are a special case of point (b) - you are still alive, but become incapable of monitoring affairs to ensure that the course of action you desire is carried out.
"All the data of your mind may still be largely intact, as appears to be the case for Alzheimer's until late in its progression, or it may be progressively and irrevocably destroyed by a disease that will have largely consumed you by the time it kills your body. Either way, a lot of entirely disreputable things happen behind closed doors when family members are close to death and cannot look out for themselves - I'm sure we can all recall a tale or two. Which is all fine and well if it's just an inheritance fight, but when it means the difference between your brain and the data of your mind preserved well at Alcor or rotting away to guaranteed oblivion ... well, that's a much bigger deal."
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!
ON TELOMERES AND IMMUNE SYSTEM AGING
Friday, March 9, 2012
The immune system falls apart with age in ways that are as much a matter of configuration as wear and tear - it is a machine in which the programming runs awry, leading it to do the wrong things at the wrong time, or just do nothing when it should be doing something. This activity leads to damage, which in turn accelerates aging: "Immune aging is associated with loss of critical immune functions, such as host protection from infection and malignancy. Unexpectedly, immunosenescence also renders the host susceptible to inflammation, which may translate into tissue-damaging disease as the senescent immune system loses its ability to maximize inflammatory protection while minimizing inflammatory injury. On the other hand, chronic inflammation associated with immune-mediated disease represents a profound stress factor for the immune system, affecting cellular turn-over, replication and exhaustion. Immune cell longevity is tightly connected to the functional integrity of telomeres which are regulated by cell multiplication, exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst the few cell types that can actively elongate telomeres through the action of telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA), telomerase deficiency is associated with prematurity of immune aging. Patients with RA have other defects in DNA repair mechanisms, including the kinase Ataxia telangiectasia mutated (ATM), critically involved in the repair of DNA double strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of telomeric length and structure are beginning to be understood and have distinct patterns in different autoimmune diseases, suggesting a multitude of molecular mechanisms defining the interface between chronic immune stimulation and progressive aging of the immune system."
ANTIBODIES VERSUS ALZHEIMER'S DISEASE
Friday, March 9, 2012
Via EurekAlert!: "Alzheimer's disease is characterized by abnormal deposits in the brain of the protein Amyloid-ß, which induces the loss of connections between neurons, called synapses. Now, scientists [have] discovered that specific antibodies that block the function of a related protein, called Dkk1, are able to completely suppress the toxic effect of Amyloid-ß on synapses. ... Dkk1 is elevated in the brain biopsies of people with Alzheimer's disease but the significance of these findings was previously unknown. Scientists [have] found that Amyloid-ß causes the production of Dkk1, which in turn induces the dismantling of synapses (the connections between neurons) in the hippocampus, an area of the brain implicated in learning and memory. ... scientists conducted experiments to look at the progression of synapse disintegration of the hippocampus after exposure to Amyloid-ß, using brain slices from mice. They were able to monitor how many synapses survived in the presence of a specific antibody which targets Dkk1, compared to how many synapses were viable without the antibody. The results show that the neurons that were exposed to the antibody remained healthy, with no synaptic disintegration."
ON POLITICS AND THE TRANSITION TO REJUVENATION BIOTECHNOLOGY
Thursday, March 8, 2012
You'll find some thoughts on incentives, politicians, and longevity science over at h+ Magazine. I don't agree with all of them, but then my views on the state as a millstone hung upon the neck of medical progress are known: "After finding out I was an economist, [Aubrey de Grey] effectively challenged me to work out what we should want politicians to do ... With over 150,000 people dying every day, I hope governments would respond to the animal experiments by accelerating our journey to [actuarial] escape velocity through massively increasing funding for longevity medical research, because the cost of dying this year goes way up if it causes you to just miss out on the chance to live long enough to live forever. But since a rational world would already make abolishing death a top priority, we can't count on politicians automatically doing this. Still (as I will explain at the end of this article) people will likely be made aware of any inevitable approach to escape velocity which should cause at least some voters to reward politicians who increase taxpayer support for medical research. ... Once we actually reach escape velocity, U.S. politicians would face enormous political pressure to make the necessary medical treatments available to all Americans, regardless of income. The U.S. government might well do this by limiting how much companies could charge for the needed medicines. Predicting this, pharmaceutical companies would have fewer incentives to develop the cures in the first place."
PARTIALLY REVERSING KIDNEY DAMAGE IN MICE
Thursday, March 8, 2012
Via EurekAlert!: "This paper reports the discovery of one of the first targeted drugs specifically developed to reverse fibrosis and regenerate the kidney. We're optimistic about the benefits, but the real proof will come from clinical testing. ... In the kidneys and other organs, fibrosis develops from normal repair mechanisms that do not stop. Scar tissue slowly builds up and replaces the working cells of the organ. In 2003, [researchers] reported that the destructive fibrosis in mice can be countered by the human protein BMP-7, originally named for its ability to spur bone growth. ... However, the large protein needs to be injected or surgically implanted and, therefore, is not useful for long-term treatment protocols. Probing deeper into the biology of the kidney, they identified the protein Alk3 [and] based on the details about the molecular interaction between the BMP protein and the ALK receptor, [scientists] developed a class of small functional peptides, including THR-123, which then underwent further testing. ... This receptor must be present for the new molecule to function ... Working through the receptor, the molecule suppressed inflammation, cell death and fibrosis formation, as well as reversing established fibrosis and allowing kidneys to regenerate functional cells ... Further experiments showed that the test drug worked even better in the mice when given in combination with ACE inhibitors, the anti-hypertensive drugs now considered a standard therapy for chronic kidney disease which work by targeting another molecular process. ... Targeting the receptor not only stops fibrosis, it removes established fibrosis, and it works in combination with an existing drug used in patients. The next step is to test this molecule in the clinic."
A CANCER SUPPRESSION MUTATION THAT ALSO EXTENDS LIFE
Wednesday, March 7, 2012
Most known cancer suppression genes and mutations shorten life in laboratory mice, as they suppress the mechanisms of cell replication needed to maintain tissues. There are exceptions that have emerged as researchers find more sophisticated methods of genetic engineering to work around these limitations, but this life-extending example of gene engineering seems to be more straightforward than most: "Mice with an extra dose of a known anti-cancer gene lose weight even as their appetites grow. Not only that, but [the] animals also live longer, and that isn't just because they aren't getting cancer, either. ... One of the animals' youthful secrets is hyperactive brown fat, which burns energy instead of storing it. The findings add to evidence that tumor suppressors aren't designed only to protect us against cancer, the researchers say. They also point to new treatment strategies aimed to boost brown fat and fight aging. ... Tumor suppressors are actually genes that have been used by evolution to protect us from all kinds of abnormalities. ... In this case, the researchers studied a tumor suppressor commonly lost in human cancers. Mice with an extra copy of the gene known as Pten didn't get cancer, but that's not the half of it. Those mice were also leaner, even as they ate more than controls ... That suggested that the animals were experiencing some sort of metabolic imbalance - and a beneficial one at that. Cancer protection aside, the animals lived longer than usual. They were also less prone to insulin resistance and had less fat in their livers. Those benefits seem to trace back to the fact that those Pten mice were burning more calories thanks to overactive brown fat."
AN INFLAMMATION MARKER CORRELATES WELL WITH MORTALITY RATES
Wednesday, March 7, 2012
Here is one of many clear signs to show that chronic inflammation is something to be avoided: "Inflammation, oxidative damage, and platelet activation are hypothesized biological mechanisms driving the disablement process. The aim of the present study is to assess whether biomarkers representing these mechanisms predicted major adverse health-related events in older persons. ... Data are from 2,234 community-dwelling nondisabled older persons enrolled in the Health Aging and Body Composition study. Biomarkers of lipid peroxidation, platelet activation, and inflammation (serum concentrations of interleukin-6) were considered as independent variables of interest and tested in Cox proportional hazard models as predictors of (severe) mobility disability and overall mortality. ... The sample's (women 48.0%, whites 64.3%) mean age was 74.6 (SD 2.9) years. During the follow-up (median 11.4 years), 792 (35.5%), 269 (12.0%), and 942 (42.2%) events of mobility disability, severe mobility disability, and mortality occurred, respectively. ... Only interleukin-6 showed significant independent associations with the onset of all the study outcomes. ... The inflammatory marker interleukin-6 is confirmed to be a robust predictor for the onset of negative health-related events."
ADJUSTING REGENERATION IN THE LIVER TO BENEFICIAL EFFECT
Tuesday, March 6, 2012
Even marginally better control over the actions of cells can improve regenerative processes in the body: "Scientists were able to unpick the process of how different cells in the liver are formed. When the liver is damaged it produces too many bile duct cells and not enough cells called hepatocytes, which the liver needs to repair damaged tissue. They found they could increase the number of hepatocyte cells - which detoxify the liver - by encouraging these cells to be produced instead of bile duct cells. Understanding how liver cells are formed could help to develop drugs to encourage the production of hepatocytes to repair liver tissue. This could eventually ease the pressure on waiting lists for liver transplants. ... The production of hepatocyte cells was increased by altering the expression of certain genes in early stage liver cells. ... This research helps us know how to increase numbers of cells that are needed for healthy liver function and could pave the way for finding drugs that help liver repair. Understanding the process in which cells in the liver are formed is key in looking at ways to repair damaged liver tissue."
WORKING ON EFFICIENT STEM CELL REPAIR OF THE CORNEA
Tuesday, March 6, 2012
Another of a number of research groups here works towards repair of damaged corneas with stem cells: researchers "have used defective corneas obtained ... [to show] how human stem cells can be caused to develop into what are known as 'epithelial cells' after 16 days' culture in the laboratory and a further 6 days' culture on a cornea. It is the epithelial cells that maintain the transparency of the cornea. ... Similar experiments have been carried out on animals, but this is the first time that stem cells have been grown on damaged human corneas. It means that we have taken the first step towards being able to use stem cells to treat damaged corneas ... If we can establish a routine method for this, the availability of material for patients who need a new cornea will be essentially unlimited. Both the surgical procedures and the aftercare will also become much more simple." While this is not the first time that stem cells have been used to repair a cornea, this sort of infrastructural work that aims to reduce cost of materials and improve efficiency of a therapeutic process is nonetheless an important step along the way to making a new therapy widely available.
PARKINSON'S AGGREGATES BLOCKED IN ZEBRAFISH MODEL
Monday, March 5, 2012
The aggregation of α-synuclein that contributes to Parkinson's disease has been blocked in an animal model of the condition, which is promising but needs much more testing: researchers "report the development of a novel compound known as a 'molecular tweezer,' which in a living animal model blocked α-synuclein aggregates from forming, stopped the aggregates' toxicity and, further, reversed aggregates in the brain that had already formed. And the tweezers accomplished this without interfering with normal brain function. ... finding a therapy that targets only the aggregates is a complicated process ... In Parkinson's, for example, the protein implicated in the disorder, α-synuclein, is naturally ubiquitous throughout the brain. ... Its normal function is not well understood, but it may play a role in aiding communication between neurons. The trick, then, is to prevent the α-synuclein protein aggregates and their toxicity without destroying α-synuclein's normal function, along with, of course, other healthy areas of the brain. [The researchers used] a particular molecular tweezer he had developed called CLR01. Molecular tweezers are complex molecular compounds that are capable of binding to other proteins. Shaped like the letter 'C,' these compounds wrap around chains of lysine, a basic amino acid that is a constituent of most proteins. Working first in cell cultures, the researchers found that CLR01 was able to prevent α-synuclein from forming aggregates, prevent toxicity and even break up existing aggregates. ... The researchers next tried their tweezers in a living animal, the zebrafish ... Using a transgenic zebrafish model for Parkinson's disease, the researchers added CLR01 and used fluorescent proteins to track the tweezer's effect on the aggregations. They found that, just as in cell cultures, CLR01 prevented α-synuclein aggregation and neuronal death, thus stopping the progression of the disorder in the living animal model."
ON VETERINARY PRACTICE AS THE FIRST BENEFICIARY OF NEW MEDICINE
Monday, March 5, 2012
The stifling regulation attending medical research and development ensures that veterinary medicine is years ahead of human medicine: "Products in the veterinary medical space can be brought to market more rapidly, iterated upon more rapidly, and therefore improved more rapidly. With owners eager to try new treatments, lower barriers to entry for new products, and far less risk of lawsuits dogs and other pets offer great advantages for development of therapies. ... Owners of pets who try assorted stem cell therapies, gene therapies, and the like have information that is now not being collected systematically. That's a great lost opportunity and the opportunity will grow with each new treatment that reaches the veterinary market. If vets could also report information then test results could be combined with owner observations (e.g. did Fido start running again after stem cells injected into joints?) then the efficacy (or lack of efficacy) of therapies could be discovered much more rapidly. This ties into a bigger problem: As things stand today truly objective medical research is much rarer than generally appreciated. We need basically open source medical research with large amounts of data collected independent of companies that develop drugs and other treatments. Given enough software and some group (could be mostly volunteers) to manage a web site to collect pet medical histories many others could analyze the data. Pets are also great for research information collection because with pets privacy isn't a big consideration. My guess is most people won't mind having their pet's medical history made public if they can see a benefit for their current and future pets and for humans as well. Given public availability of the data a far larger number of people with requisite training in statistics, medicine (veterinary or otherwise), and biological sciences could do analyses and discover patterns in the data."