Fight Aging! Newsletter, February 21st 2011

February 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!



- 25 Scientific Ideas of Life Extension
- An Editorial on Death and Ageism
- How Reversible is Alzheimer's Disease?
- A Podcast Interview With Aubrey de Grey
- Discussion
- Latest Headlines from Fight Aging!


The Russian parallel to the SENS Foundation and Methuselah Foundation is an organization called the Science for Life Extension Foundation. Amongst other activities, the Foundation volunteers publish a number of high quality PDFs on aging, human biochemistry, and longevity science. Not all of which are in English, unfortunately, but in the following post I point out one of the better ones:

"I did want to direct your attention to one of the documents, however, which is entitled '25 Scientific Ideas of Life Extension.' It is a very elegantly designed, very clear booklet aimed at investors. The PDF packages up a series of scientific research programs aimed at extending human life into compelling elevator pitches - but just saying that doesn't do it justice. It really is very well done indeed, and you should take a look."


We live in a world in which people are dying all the time and all around us - a fact that we spend a great deal of effort ignoring. Most of those deaths are the elderly, and what does it say about us that we try hard to pay no attention?

"Aging kills people, just as cars do. There are only two things that distinguish aging from other killers: it kills people very slowly, only after gradually and progressively debilitating them over many years, and it only kills people who were born quite a long time ago. The combination of these features seems to be the only available explanation for why we so meekly and calmly accept the deaths of so vast a number of people from aging, while feeling much more intense anger and despair at the comparatively rare deaths that occur in the industrialized world at younger ages. ... Is it somehow OK, or at least only a little bit sad, when someone dies of 'natural causes' after 'a good innings'? I would suggest that it is not OK.

"Ageism permeates our societies, and our descendants will look back in disgust and horror at the way in which we allowed our historical legacy of prejudice to suppress and slow down progress towards the biotechnologies of rejuvenation. We younger folk write off the old in so many ways, and in doing so each of us is only sticking the knife into the person we'll be a few decades down the line - and teaching our children to do exactly the same. Every death is a tragedy, but so many people work so hard to pretend otherwise."


The evidence to date suggests that the debilitating effects of Alzheimer's disease are in fact largely reversible in principle, at least in the early and mid stages of the condition. All we lack are good methods of bringing about that reversal:

"Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease - in part, at least."


Biomedical gerontologist and longevity advocate Aubrey de Grey should need no introductions for this audience. You'll find links to a recent interview with de Grey in the Fight Aging! post linked below:

"During this conversation I ask Dr. de Grey to discuss issues such as: the term natural death and its impact; the publicity and importance of two long-awaited documentaries about Ray Kurzweil - Transcendent Man and The Singularity is Near; traditional metabolic and more recent DNA tests such as the ones done by 23andMe and others; the slow developmental process of new drugs and therapies, and the problems of taking them from testing in lab rats to humans; the Thomas Malthus argument of overpopulation and Aubrey's reply to it."


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, February 18, 2011
The investigation of the mechanisms of calorie restriction continues apace. Here, researchers "report for the first time that deactivation of a protein called CRTC1 in roundworms increases their lifespan, most likely mediating the effects of calorie restriction. Previously, researchers knew hunger promoted longevity by activating an enzyme called AMPK, which senses that food is scarce and pushes cells into a low energy state. ... We knew AMPK was a major energy sensor but didn't know what it was talking to. Our goal was to understand the genetic circuitry that registered that response. ... It was clear that one pathway that coordinated metabolism with growth in response to nutrients was AMPK signaling. Studies had also suggested that AMPK might regulate lifespan in worms. What was not known was what factors downstream of AMPK mediated those effects. ... they searched the genome of Caenorhabditis elegans for likely AMPK targets, and identified one suspect encoding a protein called CRTC1, which was expressed at the same time and place as AMPK. To determine if CRTC1 played any role in lifespan, the team fed worms an inhibitory RNA engineered to deplete them of CRTC1 protein. When they measured the worms' lifespan-normally about 3 weeks-they found that worms fed the anti-CRTC1 RNA lived a whopping 40% longer, suggesting that AMPK retards aging by antagonizing CRTC1 activity. ... AMPK deactivated CRTC1 by adding phosphates to a specific region of the CRTC1 protein, an effect equivalent to eliminating CRTC1 altogether. Likewise, when the worms were fed an inhibitory RNA depleting them of an enzyme that lops off the CRTC1 phosphates, they lived longer, showing that AMPK and the lopper - known to scientists as calcineurin - determine lifespan by controlling the extent to which CRTC1 is phosphorylated."

Friday, February 18, 2011
From ScienceDaily: "It has been long known that stress plays a part not just in the graying of hair but in hair loss as well. ... Now, a team [that] was investigating how stress affects gastrointestinal function may have found a chemical compound that induces hair growth by blocking a stress-related hormone associated with hair loss - entirely by accident. ... Our findings show that a short-duration treatment with this compound causes an astounding long-term hair regrowth in chronically stressed mutant mice. This could open new venues to treat hair loss in humans through the modulation of the stress hormone receptors, particularly hair loss related to chronic stress and aging. ... the researchers had been using mice that were genetically altered to overproduce a stress hormone called corticotrophin-releasing factor, or CRF. As these mice age, they lose hair and eventually become bald on their backs, making them visually distinct from their unaltered counterparts. The [researchers] had developed the chemical compound, a peptide called astressin-B, and described its ability to block the action of CRF. ... researchers injected the astressin-B into the bald mice to observe how its CRF-blocking ability affected gastrointestinal tract function. .... About three months later, the investigators returned to these mice to conduct further gastrointestinal studies and found they couldn't distinguish them from their unaltered brethren. They had regrown hair on their previously bald backs."

Thursday, February 17, 2011
From the Monterey Herald: " Within a Northeast Ohio lab, a hairless mouse is growing an ear from the cells of a Wadsworth, Ohio, preschooler. Dr. William Landis, the G. Stafford Whitby Chair of Polymer Science at the University of Akron, is leading groundbreaking, tissue-engineering research to grow human cartilage - first in the lab, now in animals and, eventually, in patients. His work is part of a fast-developing field that could help millions of patients repair injuries, replace worn body parts or fix birth defects with tissue grown from their own cells in the not-so-distant future. ... Kyle Figuray's parents agreed to be the first area participants and donors of his otherwise useless cartilage. The healthy, friendly 5-year-old was born with a congenital defect that caused the exterior ear and ear canal on his right side to develop improperly. Typically, the malformed ear cartilage is discarded as medical waste after it's removed during the first of three procedures to craft a new ear out of rib. Instead, the tissue removed [was] placed inside a vial and shared with Landis' research team, who carefully cleansed the cells and fed them special nutrients to coax them to proliferate in the lab. A few weeks later, enough cells were available for researchers to 'seed' them onto a biodegradable, biocompatible polymer scaffold. A few days later, the seeded ear scaffold was implanted under the skin of a hairless mouse ... The mouse will be studied over the next year to determine how the cells are behaving and progressing toward normal cartilage. If all goes well, the biodegradable polymer scaffold should disappear, leaving behind only Kyle's cartilage cells in the shape of an ear. The hope is that an affected person's cells someday can be harvested, seeded onto similar polymer scaffolds and implanted under the patient's own skin in the abdomen or back until they grow into replacement tissue. At that point, the new tissue could be removed and used to replace the patient's injured or defective tissue."

Thursday, February 17, 2011
Research into Laron dwarfism in a population in Ecuador has been taking place for a few years now: "People living in remote villages in Ecuador have a mutation that some biologists say may throw light on human longevity and ways to increase it. The villagers are very small, generally less than three and a half feet tall, and have a rare condition known as Laron syndrome or Laron-type dwarfism. ... though cancer was frequent among people who did not have the Laron mutation, those who did have it almost never got cancer. And they never developed diabetes, even though many were obese, which often brings on the condition. ... [this is] an opportunity to explore in people the genetic mutations that researchers [found] could make laboratory animals live much longer than usual. ... The Laron patients' mutation means that their growth hormone receptor lacks the last eight units of its exterior region, so it cannot react to growth hormone. In normal children, growth hormone makes the cells of the liver churn out another hormone, called insulinlike growth factor, or IGF-1, and this hormone makes the children grow. If the Laron patients are given doses of IGF-1 before puberty, they can grow to fairly normal height. This is where the physiology of the Laron patients links up with the longevity studies that researchers have been pursuing with laboratory animals. IGF-1 is part of an ancient signaling pathway that exists in the laboratory roundworm as well as in people. The gene that makes the receptor for IGF-1 in the roundworm is called DAF-2. And worms in which this gene is knocked out live twice as long as normal."

Wednesday, February 16, 2011
A promising open access study: "Transplanting autologous renal progenitor cells (RPCs), (kidney stem cells derived from self-donors), into rat models with kidney damage from pyelonephritis - a type of urinary infection that has reached the kidney - has been found to improve kidney structure and function. ... Advancements in stem cell therapies and tissue engineering hold great promise for regenerative nephrology. Our RPC transplant study demonstrated benefits for pyelonephritis, a disease characterized by severe inflammation, renal function impairment and eventual scarring, and which remains a major cause of end-stage-renal disease worldwide. ... The researchers divided 27 rats into three groups, two of which were modeled with an induced pyelonephritis in their right kidneys, while the third group did not have induced disease. RPCs were obtained from the diseased animals' left kidneys and injected into the right kidney six weeks later. Two weeks after injection, tubular atrophy was reduced. After four weeks, fibrosis was reduced and after sixty days, right renal tissue integrity was 'significantly improved.' ... We propose that kidney augmentation was mainly due to functional tissue regeneration following cellular transplantation. Kidney-specific stem/progenitor cells might be the most appropriate candidates for transplantation because of their inherent organ-specific differentiation and their capacity to modulate tissue remodeling in chronic nephropathies. ... The researchers concluded that because renal fibrosis is a common and ultimate pathway leading to end-stage renal disease, amelioration of fibrosis might be of major clinical relevance."

Wednesday, February 16, 2011
From the Telegraph: "India's first set of government-approved clinical trials of stem cells on patients with chronic obstructive lung disease, diabetes, liver cirrhosis and osteoarthritis are likely to begin in five cities in April this year. A Bangalore-based company, Stempeutics Research, has received approval from the country's drug regulatory agency to evaluate the efficacy of its stem cells on these four incurable diseases after safety assessments over the past year on patients with cardiovascular disease. The efficacy - Phase II - trials are likely to begin on small groups of volunteer patients offered the experimental treatment in collaborating hospitals in Bangalore, Kochi, Delhi, Mangalore and Manipal, a senior Stempeutics official said. Each volunteer patient will receive a dose of mesenchymal stem cells derived from the bone marrow of healthy persons. The stem cells, coaxed to proliferate in a broth of laboratory biochemicals, will be injected at the site of illness - the pancreas, the liver, the lungs, or the bone - where they are expected to stimulate resident stem cells and regenerate the damaged or lost tissue. While private and even government hospitals have in the past offered stem cell therapy to patients with intractable conditions, the proposal by Stempeutics is the first with formal approval from regulators for chronic obstructive pulmonary disease (COPD), diabetes, liver cirrhosis and osteoarthritis."Link:

Tuesday, February 15, 2011
The selective destruction of immune cells in the old should greatly improve their failing immune function. Much of that decline results from an imbalance of cell types, while other issues such as autoimmune diseases may be the result of a small population of misconfigured cells: "Aberrant production of autoantibodies by inappropriately self-reactive plasma cells is an inherent characteristic of autoimmune diseases. Several therapeutic strategies aim to deplete the plasma cell pool, or to prevent maturation of B cells into plasma cells. However, accepted views of B-cell biology are changing; recent findings show that long-lived plasma cells [contribute] to the maintenance of humoral memory and, in autoimmunity, to autoreactive memory. As a consequence of their longevity and persistence, long-lived plasma cells can support chronic inflammatory processes in autoimmune diseases by continuously secreting pathogenic antibodies, and they can contribute to flares of symptoms. As long-lived plasma cells are not sufficiently eliminated by current therapies, these findings are extremely relevant to the development of novel concepts for the treatment of autoimmune diseases. Thus, long-lived plasma cells appear to be a promising new therapeutic target." It would be a good day for a great many patients if it turns out that autoimmune diseases can be eliminated or greatly reduced in severity by destroying just a small population of cells. We already know that complete destruction and recreation of the immune system works, so this seems like a reasonable direction to explore.

Tuesday, February 15, 2011
Some thoughts on wrong directions in medicine from Chronosphere: "The first thing that anyone needs to understand about medicine is what its proper goal is. That's actually pretty simple: to cure disease and maintain good health. No further qualifications are necessary. Once that proposition is accepted, it then should become obvious that the end goal, and the ultimate ideal of medicine, is to keep people alive and in good health indefinitely. ... So, despite the fact that most people, when asked, will recoil in horror from the notion of personal, biological immortality, the fact is that that is exactly what they expect, exactly what they want, and exactly what they will effectively demand. Unfortunately, most of the medicine we practice today is not only not going to provide immortality any time soon ... Halfway technology represents the kinds of things that must be done after the fact, in efforts to compensate for the incapacitating effects of certain diseases whose course one is unable to do very much about. By its nature, it is at the same time highly sophisticated and profoundly primitive ... It is characteristic of this kind of technology that it costs an enormous amount of money and requires a continuing expansion of hospital facilities ... It is when physicians are bogged down by their incomplete technologies, by the innumerable things they are obliged to do in medicine, when they lack a clear understanding of disease mechanisms, that the deficiencies of the health-care system are most conspicuous ... The only thing that can move medicine away from this level of technology is new information, and the only imaginable source of this information is research. The real high technology of medicine comes as the result of a genuine understanding of disease mechanisms and when it becomes available, it is relatively inexpensive, relatively simple, and relatively easy to deliver."

Monday, February 14, 2011
Via EurekAlert!: "Scientists [have] produced the first known compound to show significant effectiveness in protecting brain cells directly affected by Parkinson's disease, a progressive and fatal neurodegenerative disorder. Although the findings were in animal models of the disease, the effectiveness of the compound, combined with its potential to be taken orally, offers the tantalizing possibility of a potentially useful future therapy for Parkinson's disease patients. ... The new small molecule - labeled SR-3306 - is aimed at inhibiting a class of enzymes called c-jun-N-terminal kinases (JNK). Pronounced 'junk,' these enzymes have been shown to play an important role in neuron (nerve cell) survival. As such, they have become a highly viable target for drugs to treat neurodegenerative disorders such as Parkinson's disease. ... The SR-3306 compound, which has been in development [for] several years, performed well in both cell culture and animal models. In cell culture, the compound showed greater than 90 percent protection against induced cell death of primary dopaminergic neurons, while in mouse models of induced neuron death, the compound showed protective levels of approximately 72 percent. The scientists went one step further, testing the new compound in a rat model, which duplicates the physical symptoms often seen with the human disease - a pronounced and progressive loss of motor skills. The results showed SR-3306 provided a protection level of approximately 30 percent in the brain, a level that reduced the dysfunctional motor responses by nearly 90 percent."

Monday, February 14, 2011
Lithium is known to extend life in nematode worms, though I haven't seen much further exploration of the mechanism. Here, Japanese researchers show that lithium intake is also associated with human mortality - though as for all such large statistical studies, one would want to see confirming work from other parts of the world before taking it as fact: "Lithium is a nutritionally essential trace element predominantly contained in vegetables, plant-derived foods, and drinking water. Environmental lithium exposure and concurrent nutritional intake vary considerably in different regions. We here have analyzed the possibility that low-dose lithium exposure may affect mortality in both metazoans and mammals. ... Based on a large Japanese observational cohort, we have used weighted regression analysis to identify putative effects of tap water-derived lithium uptake on overall mortality. Independently, we have exposed Caenorhabditis elegans, a small roundworm commonly used for anti-aging studies, to comparable concentrations of lithium, and have quantified mortality during this intervention. ... In humans, we find here an inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 neighboring Japanese municipalities with a total of 1,206,174 individuals ... Consistently, we find that exposure to a comparably low concentration of lithium chloride extends life span of C. elegans ... Taken together, these findings indicate that long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species."


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