Longevity Meme Newsletter, February 1 2010

February 1 2010

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- Making Old Stem Cells Act As Though Young
- The Layperson's View of Longevity Science
- An Intriguing View of Alzheimer's Disease
- Discussion
- Latest Healthy Life Extension Headlines


Stem cells are essential for the maintenance of our organs and tissues: they continually spawn normal cells to replace those lost, damaged, or worn out. Unfortunately, stem cell activity declines with age, and this is one contributing factor to the degenerating functions of our bodies. It has been known for a few years that at least some types of old stem cell can be made to act as though young again by changing their environment, however:


"Surprisingly, this age-related decline in stem cell potency may be somewhat reversible. A team of Howard Hughes Medical Institute (HHMI) researchers has found that in old mice, a several-week exposure to the blood of young mice causes their bone marrow stem cells to act 'young' again. ... The researchers have not yet isolated the blood-borne factors that can switch old stem cells back to a more youthful state, but their results are consistent with other recent studies that show stem-cell aging may be reversible. Together those results suggest that it might one day be possible to boost the practical lifespan of stem cells, and thereby increase the body's resistance to disease and age-related degeneration."


Lest we forget:


"Once you start digging into a topic, it becomes all too easy to lose sight of your previous state of knowledge, and the opinions you held before you learned more. What were your thoughts on aging research and engineered longevity before you became interested enough to start reading this blog on a regular basis? When we talk about advocacy and fundraising for projects like the Strategies for Engineered Negligible Senescence, we are really talking about convincing people who are presently where you used to be: they are potentially interested, but not in the loop, and not seeing the whole picture. If you lose sight of how these folk think - which is the same way that you used to think - then you will find it harder to persuade and educate."


Alzheimer's research is in a constant state of flux: a great deal of funding flows into this field, but there is as yet no comprehensive and defensible theory as how this disease occurs, progresses, and causes degeneration. This is not to say that there are no theories, or no evidence. Quite to the contrary - there are many, many theories and a great mass of ever-growing evidence to array for or against them all. This is what an energetic field looks like when it is on the verge of breakthroughs and understanding. The post linked below looks at one small set of theories and debates, and hopefully gives some sense of the present state of research:


"All Alzheimer's disease patients harbor some cells with three copies of chromosome 21, known as trisomy 21, instead of the usual two. Trisomy 21 is a characteristic shared by all the cells in people with the birth defect Down syndrome as well. This earlier work demonstrated that Alzheimer's disease could be considered a late onset form of Down syndrome. By age 30 to 40, all people with Down syndrome develop the same brain pathology seen in Alzheimer's disease, including a nerve-killing buildup of sticky amyloid protein clumps."

"The Alzheimer's-associated amyloid protein is the culprit that interferes with the microtubule transport system inside cells. The microtubules are responsible for segregating newly duplicated chromosomes as cells divide. ... When the microtubule network is disrupted, chromosomes can be incorrectly transported as cells divide and the result is new cells with the wrong number of chromosomes and an abnormal assortment of genes."

But can this theory be defended? At this point in the development of a field, the best way forward starts to look like putting theory into practice. Develop a drug to block the precise interaction between amyloid and microtubules and see whether it provides benefits in cell cultures and animal models, in other words. Demonstrating such benefits in the laboratory, if it can be made to work, is the grand short-cut through a daunting field theoretical considerations and further examination of Alzheimer's biochemistry.


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!




The Immortality Institute is running a creative writing contest over the next few months, with a submission deadline in March: "Throughout the history of the Immortality Institute a high priority has been placed on communication. The use of various media including graphic arts, film, and prose has always been a powerful means of disseminating ideas and the idea of life extension is no exception. This focus has led to the creation of the world's first comprehensive tome on modern scientific efforts and philosophy of immortality – The Scientific Conquest of Death, and the documentary film Exploring Life Extension (both available free online). The Immortality Institute has also sponsored writing contests. Read about the most recent non-fiction essay contest here. Winning entries here and here. It is 2010 and time again for forward-thinking individuals to put their best pen forward to communicate the ideals, vagaries, possibilities, and dreams of radical life extension, human enhancement, and immortality. Unlock your imagination and submit a story today!"

Via ScienceDaily: "Eliminating cancer stem cells (CSCs) within a tumor could hold the key to successful treatments for ovarian cancer ... Ovarian cancer has been challenging to treat because it tends to recur frequently and develop resistance to treatment. ... This recurrence and drug resistance may be due to the presence of CSCs within the tumors that have the capacity to reproduce and to differentiate into non-CSC tumor cells that repopulate the tumor mass. Eliminating these CSCs may be key to successful treatments. ... While in the process of studying the functions of stem cell proteins in human embryonic stem cells, [researchers] unexpectedly discovered that a sub-population of ovarian cancer cells express stem cell proteins Lin28 and Oct4, [both of which are known markers of embryonic or embryonic-like stem cells]. They also found that the two proteins appear to act together in ovarian cancer tissue cells to produce more advanced tumors. Inhibiting their combined expression led to a significant decrease in the growth and survival of cancer cells. A larger-scale ovarian cancer study is currently underway to confirm the significance of the findings."

At It's Rainmaking Time, you'll find an audio interview with Ben Best on the topic of cryonics: "Many of us would choose to live another 100 years or more, if we only knew how. Enter cryonics: an exciting, fascinating, and highly misunderstood scientific field. We have invited Ben Best, the president of The Cryonics Institute, to help us understand cryonics, where the paradigm is gaining traction, and the logistics involved. Join us for an illuminating discussion." Best, like many of the movers and shakers in the pro-longevity community, is a writer. You should take the time to look through the work at his personal website, especially the essays on cryonics and engineered longevity. For example, the Mechanisms of Aging essay is a fairly detailed overview is what is presently known and debated in the scientific community, whilst Why Life Extension? examines the motivations of those who want to live longer in good health and those who claim not to.

From EurekAlert!: researchers "have succeeded in the ultimate switch: transforming mouse skin cells in a laboratory dish directly into functional nerve cells with the application of just three genes. The cells make the change without first becoming a pluripotent type of stem cell - a step long thought to be required for cells to acquire new identities. ... Until recently, it's been thought that cellular specialization, or differentiation, was a one-way path: pluripotent embryonic stem cells give rise to all the cell types in the body, but as the daughter cells become more specialized, they also become more biologically isolated. Like a tree trunk splitting first into branches and then into individual leaves, the cells were believed to be consigned to one developmental fate ... The research suggests that the pluripotent stage, rather than being a required touchstone for identity-shifting cells, may simply be another possible cellular state. ... finding the right combination of cell-fate-specific genes may trigger a domino effect in the recipient cell, wiping away restrictive DNA modifications and imprinting a new developmental fate on the genomic landscape. ... It may be hard to prove. but I no longer think that [induced pluripotency] is a reversal of development. It's probably more of a direct conversion like what we're seeing here, from one cell type to another that just happens to be more embryonic-like. This tips our ideas about epigenetic regulation upside down."

While we all pay attention to end results in our own field of interest, the general infrastructure biotechnologies that enable those end results are progressing rapidly. This article illustrates just how fast one of the benchmark technologies - DNA sequencing - is moving: "Although Complete Genomics is now slated to sequence an incredible 5,000 human genomes in 2010, this is nothing compared to what the company has in store for the years ahead. ... the company is now hoping to sequence 50,000 genomes in 2011 and a whopping 1 million genomes by 2014. Considering that by the end of 2009 only about 100 or so human genomes had ever been sequenced, most of them by - you guessed it - Complete Genomics, this represents an enormous shift in the industry. ... In November of last year Complete Genomics announced that they had sequenced 3 human genomes at an average cost of materials below $5000 apiece, shattering all previous records by nearly a factor of ten! Last year Complete Genomics was charging its customers $20,000 per genome and this year they will be charging $10,000 or less. We can expect the company’s costs and the prices it charges its customers to continue to drop dramatically in the next few years. The $1,000 genome is indeed within sight."

Another good article from h+ Magazine is illustrative of the present state of the art in the DIY Bio scene: "In September 2007, I gave a short talk at Aubrey de Grey's SENS conference in Cambridge outlining my intention to found an open source biotech company that would make customized therapies for breast cancer. The response to the presentation was predictable: many had concerns whether regulators would allow such a drug to be used in a human trial. I had no idea, but I knew the only way to truly find out would be to try. It took almost two years of discussion and feeling my way around, but this company now exists. It‘s called the Pink Army Cooperative. ... Breast cancer is the first target, but ultimately the cooperative's goal is to open a path from diagnostics to the clinic for individualized medicines - to make effective cancer treatments as fast as diagnostic data can be translated into designs, manufactured, tested in the lab, and approved for use on a single person. Using open source synthetic biology, each of these steps can be automated, and each should get cheaper over time. ... Pink Army, then, is the first DIY drug company. It's a container that allows people interested in tackling cancer to connect and focus their passion, skills, and other resources."

Researchers are investigating a range of ways to restore aspects of the aged immune system to youthful levels. Here is one: "By comparing the immune responses of both, young and old mice, to bacterial infection they found that the number of macrophages, one of the major cell populations involved in the elimination of infecting bacteria, decreases rapidly in aged mice. This decline in the number of fighters and the associated weakness of the immune defense may be responsible for the age-associated increase in susceptibility to infections. [Researchers] have succeeded to enhance the resistance to an infection in aged mice by treating them with a macrophage-specific growth factor. This treatment increases the amount of macrophages in aged mice and improves their capacity to fight the infection. ... The treatment made aged mice much more resistant and they could fight much better the infection. The results of our study indicate that repeated prophylactic administration of this growth factor can help to maintain the macrophage compartment in the elderly and the fitness of the immune system."

Here's a report on a presentation given by biomedical gerontologist and engineered longevity advocate Aubrey de Grey in Finland: "All in all, I found the presentation very understandable, concise and even entertaining. Everything except maybe the part about the seven types of aging damage was understandable even for the layperson. If you have doubts about whether ending aging is desirable or possible, I very much recommend watching some of his lectures online. They're also very useful if you want to convince others that the fight against aging is an important one. One thing I noticed Aubrey does well (and I don't) is to counter arguments by people whose life philosophy is, in my opinion, grounded on bad logic. For example, he gave a good response to the religious objection that life extension is a sin, arguing that it's essentially the other way around, because not doing anything to aging is the same thing as allowing suffering, which must be wrong. ... Another important point is that unlike what people imagine their own death to be like - quick and painless - for the overwhelming majority of the world's population it is nothing of the sort. What it is is a slow decline in physical and mental capabilities followed by a complete collapse and, ultimately, death. It is a process of slow deterioration that goes on for decades, with each decade being progressively worse in terms of biological functions than the previous one. To wish such a fate upon yourself is irrational, and to wish it upon others is just evil."

An open access paper: "The notion that autophagy increases longevity is well illustrated by experiments in which the massive induction of autophagy by either pharmacological methods (such as the administration of rapamycin [Rapa] or spermidine) or genetic manipulations (like the knockdown the autophagy inhibitor p53) improves organismal survival and hence reduces age-associated mortality. Caloric restriction (which is the most physiological inducer of autophagy), Rapa (which is the best characterized pharmacological inducer of autophagy), or knockdown of the p53 ortholog cep-1, all extend the lifespan of the nematode Caenorhabditis elegans only when the autophagic machinery is intact. Thus, knockdown of AuTophaGy-related (atg) genes annihilates the longevity-enhancing effect of caloric restriction, Rapa, and p53 depletion. ... Similarly, it has been found that the lifespan-extending properties of the natural polyamine spermidine strictly rely on the activation of the autophagic program in several model organisms including yeast, nematodes, and flies."

Biotechnology will follow the path of software: it will become a low-cost open source garage industry, and thus highly innovative and competitive. Here, h+ Magazine looks at the transhumanist side of the DIY Bio movement: "Hardware hacking has a rich history, filled with geek heroes, and these skills are being turned towards the creation of biotech equipment. On the bleeding edge of it all, some DIYbiologists are applying their skills to h+ technologies. SENS researchers John Schloendorn, Tim Webb, and Kent Kemmish are conducting life-extension research for the SENS Foundation, building equipment for longevity research, saving thousands of dollars doing it themselves. The DIY SENS lab is headed by PhD candidate John Schloendorn. John is a last- year PhD student at Arizona State University. He volunteers full time for the SENS Foundation. Entering his lab was a mind-blowing experience. The ceilings were high, the lab itself was spacious and well-lit. It smelled of sawdust, the product of constructing the furniture on site. The equipment was handmade, but brilliantly so. Elegance and function were clear priorities. When a panel could be replaced with a tinted membrane, it was. When metal could be replaced by sanded wood, it was. The on-site laser was modified from a tattoo-removal system. Costs were down, but the technical skill involved in manufacturing was top notch."



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