Fight Aging! Newsletter, May 2nd 2011

May 2nd 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!



- A Vegas Group Initiative Update
- SENS Foundation is Hiring a LysoSENS Researcher
- Exploring Transdifferentiation
- Discussion
- Latest Headlines from Fight Aging!


A couple of posts this week on the Vegas Group, which is at present a few folk focused on documenting the technique of protofection and getting the organizational basics figured out - more helping hands are always welcome:

"The Vegas Group is presently a discussion list of a few active volunteers and a small crowd of interested folk. We are looking at the nuts and bolts of organization, focused on a proof of concept documentation project: take mitochondrial protofection and document it sufficiently well to make it accessible to the DIYbio community of enthusiasts and moonlighting biotech professionals who are building open-access devices and establishing shared laboratories. Along the way this means finding freelance life science writers, evangelizing the concept, proofing copy, making diagrams and layouts, and putting up a website - amongst other line items."

"We are looking for more life science and DIYbio volunteers, writers and editors, folk with connections that will help move things along, people with an understanding of the legalities of reverse engineering and intellectual property, and web developers who can help with the forthcoming website. Amongst others - if you think you can help make the Vegas Group a reality, then you probably can. So join the list and help!"

"What is the Vegas Group initiative setting out to achieve, in a nutshell? I'm still working on that short explanation, but here is one attempt at it. Thanks to the present regulatory situation in the US - where aging is not recognized as a disease, and therefore no therapy for aging can be legally developed - there are any number of potentially useful biotechnologies presently languishing without further development. These are methods and techniques shown to extend life in mice or repair and reverse specific biochemical aspects of aging, but for which there is no further funding for clinical development. Nothing may be happening for these technologies in the US, but there are active biotechnology and medical development communities in other parts of the world who are not so encumbered by local regulation: many of the developed Asia-Pacific countries, for example. What the Vegas Group initiative ultimately aims to do is build a bridge between these undeveloped technologies and the developers who could bring them into the clinic for human use."

"How will that bridge be built? I believe that the growing garage biotechnology and DIYbio communities will play a pivotal role in the US - validating, documenting, and lowering the cost for overseas ventures to pick up and further develop longevity therapies. From my perspective then, the very earliest actions for the first Vegas Group volunteers involve building the foundations for a repository of how-to documentation: guides that clearly explain how the garage biotechnology community could validate and further develop the best and latest techniques in longevity science."


The SENS Foundation is hiring a team lead for their LysoSENS medical bioremediation research project:

"LysoSENS is the SENS Foundation initiative to build a platform [capable] of breaking down the damaging byproducts of metabolism that build up in old cells and degrade their ability to recycle garbage. The short of is that we know that out there somewhere are bacteria that can eat these compounds, such as the lipofuscin that contributes to many age-related conditions. There is no buildup of prominent components of lipofuscin in graveyards, for example - so something is consuming it. That bacterial something will be armed with enzymes, biological knifes and saws that might be turned into a therapy to destroy lipofuscin if identified and introduced into the human body. ... The search for bacterial enzymes that can safely attack lipofuscin in the body presently gets the lion's share of research funding at the SENS Foundation, and, appropriately, they are hiring in the Bay Area, California."


The field of stem cell research moves rapidly and is exceedingly complex, but is in essence the story of how researchers are learning to control cells - in particular how to change cells from one type into another. Some animal species do this naturally, in ways that might be advantageous for research programs in human medicine:

"The jellyfish Turritopsis nutricula is one of the few species whose members might be considered immortal, based on what is presently known of its biology. ... The form of agelessness enjoyed by Turritopsis nutricula appears to be an adaptation to periods of starvation: it can retreat to earlier stages of its life cycle, and in the process its cells alter their character in an usual way ... Theoretically, it can repeat this process indefinitely as its cells undergo a process called transdifferentiation, a rare biological process whereby any non-stem cell can become a different cell entirely."

In recent years, researchers focused on transforming or culturing specific cell types through the intermediary stage of producing or obtaining stem cells. Thus you see a great deal of research focused on how to create stem cells from a patient's cells, or find sources of existing stem cells in the body - and then a great deal of research on how to instruct stem cells to differentiate into specific specialized cell types. But if researchers better understood the cell's instruction set, it should be possible to switch a cell's type directly without the need for stem cells:

"In recently reported research, researchers are making inroads in converting various types of cell in the pancreas - which offers the possibility of a fairly direct path towards providing new beta cells to diabetes patients ... Our work shows that beta cells and related endocrine cells can easily be converted into each other ... It had long been assumed that the identity of cells was 'locked' into place and that they could not be switched into other cell types. But recent studies have shown that some types of cells can be coaxed into changing into others - findings that have intensified interest in understanding the mechanisms that maintain beta cell identity."

Ultimately, this is all about lowering the cost of producing large numbers of any specific type of cell from easily obtained tissue samples from a patient (e.g. skin samples). The lower the cost, the more practical applications there are in a range of therapies.


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, April 29, 2011
Mitochondria are the cell's roving herd of bacteria-like power plants, and the damage they suffer in the course of their operation is strongly implicated as a contributing cause of aging. Here researchers show that calorie restriction appears to boost the rate at which new mitochondria are spawned: "mice with increased respiratory rates and reduced energetic conversion efficiency due to spontaneously uncoupled mitochondria lived longer than their counterparts. Indeed, different uncoupling strategies were able to extend lifespan in models ranging from yeast to mammals. ... uncoupling could be an approach to promote lifespan extension due to its ability to prevent the formation of reactive oxygen species (ROS). Indeed, mild mitochondrial uncoupling is a highly effective intervention to prevent the formation of ROS ... CR also increases the number of functional respiratory units (mitochondrial biogenesis) [and researchers] demonstrated that mitochondrial biogenesis was essential for many beneficial effects of dietary limitation in mice. ... We recently demonstrated that murine lifespan can be extended by low doses of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in a manner accompanied by weight loss, lower serological levels of glucose, insulin and triglycerides as well as a strong decrease in biomarkers of oxidative damage and tissue ROS release. Similar effects have been repeatedly reported using CR diets ... Based on the similarities between these two interventions, we hypothesized that DNP treatment could also lead to enhanced mitochondrial biogenesis. In this manuscript, we measured the effects of DNP treatment and CR on mitochondrial biogenesis and associated pathways. We observed that both DNP and CR increase mitochondrial biogenesis, [confirming] that signaling events in both treatments converge."

Friday, April 29, 2011
A fairly long open access commentary on metformin and its effects on slowing aging in mice: "A recent study [may] certainly establish that metformin should be defined as geroprotective or gerosuppressant rather than bona fide [calorie restriction mimetic]. Long-living female mice from the outbred SHR strain were fed metformin in drinking water beginning at 3, 9 or 15 months of age and they were then analyzed for reproductive aging, mean and maximal lifespan and incidence of malignant tumors ... In female SHR mice, [researchers] now confirm that metformin treatment, if started early in life, notably increases by 21% the mean lifespan of tumor-free mice. In contrast, if started late in life, metformin treatment appears to significantly reduce (by 13%) the mean lifespan of tumor-free mice. ... It is perhaps relevant to note that, if started early in life, metformin treatment decreased the risk of death compared to the control group whereas similar treatment with metformin at older ages did not affect the relative risk of death in SHR female mice. Metformin's ability to increase the mean lifespan of tumor-free mice while simultaneously decreasing the risk of death in an age-related manner somewhat recapitulate metformin's ability to reduce cancer incidence among type 2 diabetic individuals."

Thursday, April 28, 2011
A study of markers of oxidative stress in centenarians: "Human longevity is a complex phenotype that is determined by environment, genetics, and chance. Understanding the mechanisms by which aging leads to longevity, particularly healthy longevity would be of enormous benefit to our aging population. Unfortunately, most research on human aging has focused on phenomenological description of age-related diseases, and much less is known about the mechanisms of aging itself. Among the most promising theories about how and why we age is the Free Radical Theory, initially proposed by Denham Harman in 1956. Harman proposed that oxygen radicals produced during aerobic respiration induce oxidative damage in DNA, cells, tissues, and organisms that lead to aging and death. ... Harman hypothesized, based on observations of enzymatic redox chemistry, that oxygen radical generation occurs in vivo and that mechanisms exist to protect against such damage. Mitochondria were later found to be a principal source of these oxygen radicals ... Okinawa has among the world's longest-lived populations but oxidative stress in this population has not been well characterized. ... The low plasma level of [oxidized lipids] in Okinawan centenarians, compared to younger controls, argues for protection against oxidative stress in the centenarian population and is consistent with the predictions of the Free Radical Theory of Aging."

Thursday, April 28, 2011
An open access paper: "Aging is the single most important risk factor in human disease in developed countries but when it comes to research on prevention or cures, aging is seldom taken into account. Nevertheless if aging is a significant contributor to age-related conditions, we would hope that an understanding of aging mechanisms could prompt the design of rational therapies. Moreover, if aging causes multiple diseases then it is reasonable to think that pharmacological agents that slow aging could be also effective in preventing or slowing a wide spectrum of diseases. ... Protein aggregation is a hallmark of aging and several age-related pathologies, collectively known as conformational diseases (CD). This similarity strongly suggests a crosstalk between aging and disease. Although it is not clear how protein aggregation occurs, dramatic alterations in the balance of protein synthesis, protein folding and protein degradation (together representing 'protein homeostasis') are likely to play important roles in this process. As a consequence, modified proteins tend to accumulate into soluble oligomers and insoluble aggregates that may actively influence cell function. Neurodegenerative diseases are arguably the best studied CD and the aberrant aggregation of several insoluble molecules [has] long been associated with the development of these pathologies. ... The general picture that that has emerged is that conformationally-altered proteins escape the surveillance of repair and degradation systems, form aggregates, and this process contributes to aging; aging could be therefore a manifestation of a loss in protein homeostasis. This then prompts the question: to what extent could chemical modulation of protein aggregation alter the rate of aging? Furthermore, would such an intervention influence disease pathology? In a recent publication, we addressed this issue by identifying small molecules able to slow protein aggregation in the C. elegans model. We were then able to directly assess the degree to which protein aggregation influences normal aging rates."

Wednesday, April 27, 2011
A translated interview with SENS Foundation co-founder Aubrey de Grey: "I have identified seven types of damage [that cause aging]. In five cases we can repair the damage in my opinion, by replacing irreversibly damaged cells by stem cells, or when garbage accumulates, we will remove [it]. In two cases, we need to engage in gene therapy, for example, through new DNA counteract mutations in the mitochondria. ... We should intervene as little as possible in the metabolic pathways themselves. This is too complicated, we do not know enough yet about it. I prefer the regenerative approach, the repair and maintenance. It is [sufficient] to repair the damage after it occurred. In this way, we do not [need to] understand all the molecular details and how they come about. But we have to intervene before the problems get out of control. ... A simple example is the stiffening of the extracellular matrix - this is the fibrous scaffold between cells. The stiffening occurs because certain molecules network with each other. There is a principal [agent], a molecule called [glucosepane], which has the largest share of the networking and reinforcement. We must find a way to break up about two-thirds of them again. If we break these reinforcements, it would eliminate about half of the damage. ... I think the probability is about 50 percent, that all of these therapies in 25 years actually show the desired results. The average life span might then be [increased by] about 30 years."

Wednesday, April 27, 2011
News from the field of stem cell research: "researchers [report] a game-changing advance in stem cell science: the creation of long-term, self-renewing, primitive neural precursor cells from human embryonic stem cells (hESCs) that can be directed to become many types of neuron without increased risk of tumor formation. ... It means we can generate stable, renewable neural stem cells or downstream products quickly, in great quantities and in a clinical grade - millions in less than a week - that can be used for clinical trials and, eventually, for clinical treatments. Until now, that has not been possible. ... Human embryonic stem cells hold great promise in regenerative medicine due to their ability to become any kind of cell needed to repair and restore damaged tissues. But the potential of hESCs has been constrained by a number of practical problems, not least among them the difficulty of growing sufficient quantities of stable, usable cells and the risk that some of these cells might form tumors. ... [Researchers] added small molecules in a chemically defined culture condition that induces hESCs to become primitive neural precursor cells, but then halts the further differentiation process. ... And because it doesn't use any gene transfer technologies or exogenous cell products, there's minimal risk of introducing mutations or outside contamination."

Tuesday, April 26, 2011
An article on uploading and preservation of the brain: "Ken Hayworth, a cognitive neuroscientist, has the difficult task of juggling two hats on his head, or should we say brain. With the first one, he and his colleagues at Harvard University are working on enhancing the power of an instrument that automates the mapping of brain tissues to answer a fundamental question that still faces neuroscience: How are the 100 billion neurons wired in the brain and how they know what function to perform? If you think that's difficult to digest, ponder over the bigger objective that Hayworth has on his mind - not as a Harvard post-doctoral student but as the president of The Brain Preservation Foundation: 'My personal long-term goal is to upload a human mind into a machine. I think it's the larger conclusion of neuroscience. This means, I can put a specific mind into a robot.' ... In the next five years, he is confident of seeing an entire human brain preserved chemically and embedded in plastic. This brain, he explains, can eventually be automatically cut into ultra-thin strips and scanned at very fast rates and high resolutions. With these maps, neuroscientists can figure out how the neurons are wired and how they create memories, skills and personalities. ... Hayworth is convinced that once the scientific and medical community understands that brain preservation techniques (cryonics or plastination) are successful in preserving 'high-quality brains', people will come around the idea eventually. He admits, though, that legal problems will remain (currently, one can't preserve a brain before a person is legally dead). Regardless, he has announced a prize of $106,000 to anyone who can preserve a large mammalian brain such that all the synaptic connections are intact using today's technology. Two major laboratories are competing for the prize, says Hayworth, adding: 'We have to image that brain and verify that claim ourselves. For this, we will need the help of labs and more money. Currently, I have zero money in the bank.' But he is optimistic that "this message will resonate. 'I have been talking to some very wealthy people (who do not want to disclose their identities currently). They believe in this and want to see credibility. Once people start seeing results in brain preservation, there will be more converts.'"

Tuesday, April 26, 2011
An interesting technology demonstration noted at the Technology Review:: "Viruses can deliver light-sensitive proteins to specific cells in the retinas of blind mice, allowing rudimentary vision, according to new research. ... The new light-sensitive proteins were active for the length of the study, about 10 months, suggesting the treatment would work long-term. In addition, the therapy appeared safe; the proteins, which were derived from algae, remained within the eye, and they did not trigger inflammation. ... In my opinion, the biggest step forward in this paper is the use of viral delivery techniques, the same delivery techniques that would have to be used should the technique move on into human treatment. ... Recent gene-therapy studies, which used similar viruses to deliver different proteins, have shown preliminary success in treating a rare genetic form of blindness in patients.But the current approach could be applied to a much broader group of people because it could restore light-sensitivity to the retina regardless of the cause of degeneration. .. [Researchers] used a specially designed virus to deliver numerous copies of the gene that makes a protein called channelrhodopsin to the eye. The protein forms a channel that sits on a cell's membrane and opens when exposed to light. Positively charged ions then rush into the cell, triggering an electrical message that is transferred to other cells in the retina. The gene was modified so that it became active only in specific retinal cells called bipolar cells. In a healthy eye, these cells are activated when adjacent photoreceptor cells detect light. The researchers hope that making the bipolar cells directly responsive to light in an eye stricken by retinal degenerative diseases, such as retinitis pigmentosa or macular degeneration, could enable the altered cells to replace photoreceptors that have died off. "

Monday, April 25, 2011
A Russian group has been investigating the effects of GADD45 on life span in flies, which I noted last year. Here is a post from one of the researchers outlining the present state of research: "As I wrote earlier, we were able to do while his most important discovery - show that activation of the GADD45 gene by genetic methods leads to longer life of fruit flies up to 80%. Our research also showed that in old age animals are not able to activate their own GADD45, which leads to deterioration of stress resistance and aging (article forthcoming). Transcription factor FOXO, which plays a role in anti-aging generally known (it provides the ability to handle stress, suppressed IGF-1 signaling), causes DNA repair through GADD45. GADD45 is controlled by another gene of longevity - SIRT1. We are now looking for investors to look for substances capable of restoring expression of the gene GADD45 in older individuals to the level inherent in the young. ... Ability of cells to maintain a high level of inducible GADD45 with age could be an excellent marker for longevity of the individual. To prove this, it is necessary to conduct a screening study among different age groups and centenarians." We will see a lot of this in the years ahead: the financial success achieved by researchers in the field of sirtuins, despite a lack of practical results, will attract a great many research groups to try to slow aging through metabolic manipulation. Unfortunately this is the long, hard path to a poor end goal: as a strategy for tackling aging it is a bad choice when compared to the Strategies for Engineered Negligible Senescence.

Monday, April 25, 2011
Thanks to the present restrictive state of medical regulation, horses have been getting better treatments than people for a few years now: "Take the case of SandSunSea, a 3-year-old colt by the late Pleasant Tap, bought for about $90,000 at a yearling sale in Canada. His trainer, Roger Attfield, elected not to try racing him at age 2. 'He was a horse that I gave time to because he was a big growing boy,' Attfield said. At 3, the colt was coming along nicely but then suffered a torn flexor tendon in his right front leg. 'He was just about ready to run when this happened.' ... Such an injury normally would take nine months to a year to recover from, and the horse might re-injure himself once he finally goes back into training. Attfield turned to stem-cell therapy. He shipped the horse from Payson Park training center in Florida to Woodford Equine Hospital in Versailles, where Dr. Joe Yocum removed a bit of the horse's tissue one morning in March. At the MediVet labs, which opened earlier this year in Nicholasville, 1.2 billion stem cells were pulled from 30 grams of fat taken from SandSunSea. ... That afternoon some of the cells were injected back into SandSunSea's leg. (The rest are stored frozen at the MediVet lab in case more treatments are needed one day.) The results surprised even Yocum, who is a partner in MediVet America, one of a handful of companies around the world that offer stem-cell therapy to veterinarians. 'I went back after two weeks and scanned him and could hardly even find the lesion. He looks perfect, really.' Normally it might take four months for the lesion to gradually disappear, he said. 'This thing was practically obliterated in two weeks.'"



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