FIGHT AGING! NEWSLETTER
September 19th 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!
- First Official SENS5 Videos Posted
- Of Rats, Pigeons, and Cell Membranes
- Is the Study of Accelerated Aging Conditions Relevant?
- Latest Headlines from Fight Aging!
FIRST OFFICIAL SENS5 VIDEOS POSTED
The SENS Foundation volunteers are processing video of the presentations at the SENS5 conference held a few weeks ago:
"The SENS Foundation volunteers are doing a great job on the video for this year's SENS5 conference, a gathering of researchers working on the foundations of rejuvenation biotechnology that was held at the start of this month. Take a look at the traditional conference photo, which is pretty much a who's who of the cutting edge of aging and longevity research, as well as important figures from the cryonics industry, funding groups, and advocacy community. The Foundation has opened a YouTube channel for conference video, and the first ones through the pipeline are posted. I recommend starting with the SENS Foundation CEO's presentation, which is a good overview of the SENS agenda and progress for the layperson."
"We age in part because a small number of important genes in our mitochondria are broken over time by the polluting effects of their day to day operation: broken genes mean the protein machines produced from their blueprints are also broken, or cannot be produced at all. ... The MitoSENS strategy is twofold: (a) gene therapy to copy the few important mitochondrial genes into the cell nucleus, known as allotopic expression, and (b) one of a range of clever biotechnological strategies to get the protein machinery produced from those gene blueprints from the nucleus back out to the mitochondria where it is needed. You might look at the work of Corral-Debrinsky's group to see this in action in a real research program: when you have nuclear copies of mitochondrial genes, it doesn't matter if the more vulnerable mitochondrial versions suffer mishaps, everything continues as before. ... A further good introduction to this topic and the work of the SENS Foundation is spurring this research can be found in video recorded at the recent SENS5 conference. Conference videos are being posted to the SENS Foundation YouTube channel as they are processed, and here is an educational presentation on the state of allotopic expression of mitochondrial genes."
OF RATS, PIGEONS, AND CELL MEMBRANES
The comparative study of rats and pigeons tells us something about the way in which biology determines life span. Pigeons live seven times longer than rats, and we might well ask why that happens:
"We have revisited the rat-pigeon comparison in the most comprehensive manner to date. We have measured superoxide production (by heart, skeletal muscle and liver mitochondria), five different antioxidants in plasma, three tissues and mitochondria, membrane fatty acid composition (in seven tissues and three mitochondria), and biomarkers of oxidative damage. The only substantial and consistent difference that we have observed between rats and pigeons is their membrane fatty acid composition, with rats having membranes that are more susceptible to damage.
"That's a pretty good piece of supporting evidence for the membrane pacemaker hypothesis of aging: longer lived species are longer lived because their cellular membranes are more resistant to damage. This ties in nicely to the role of mitochondria and mitochondrial damage in aging: swarming mitochondria in cells churn out damaging free radicals as a consequence of their day to day operations, and as a consequence damage themselves in ways that spiral out to cause all sorts of harm in the long term. If a species is more resistant to that damage in the places where it matters the most, then it lives longer.
"As I have said before, I tend to view this as support for the importance of mitochondrial repair research. If resistant mitochondria give pigeons even a fair chunk of that multiplier of seven over rat life spans, then how much further could the research community take things if armed with a way to completely fix the self-inflicted mitochondrial damage rather than just resist it?"
IS THE STUDY OF ACCELERATED AGING CONDITIONS RELEVANT?
What is the value of studying accelerated aging conditions? Will it lead to important realizations regarding normal aging? These remain open questions:
"There are several rare conditions that present the appearance of accelerated aging, the changes they cause extending far enough down into the fundamentals of human biochemistry that there yet remains much to learn about their operation and some debate over whether they are in fact forms of greatly accelerated aging. The best known of these conditions are Hutchinson-Gilford Progeria (HGPS, or just progeria) and Werner syndrome; significant progress has been made in identifying their root causes over the past decade, but that is still a way removed from knowing whether there is any great relevance there insofar as concerns research into ordinary aging."
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!
HORMESIS, CELL DEATH, AND AGING
Friday, September 16, 2011
A short open access paper: "Hormesis (a neologism coined from the ancient Greek term hormáein, which literally means 'to set in motion, impel, urge on') describes a favorable biological response to harmless doses of toxins and other stressors. Hormesis-stimulating compounds initiate an adaptive stress response that renders cells/organisms resistant against high (and normally harmful) doses of the same agent. On the theoretical level, hormesis may constitute (one of) the mechanisms that allows stressed cells to avoid senescence and death, and hence might have some impact on the (patho)physiology of aging. Thus, measures that reportedly prolong the healthy lifespan of multiple species, such as caloric restriction and the administration of resveratrol, may do so by inducing a hormetic response ... [Hormesis] is best represented by ischemic preconditioning, the situation in which short ischemic episodes protect the brain and the heart against prolonged shortage of oxygen and nutrients. Many molecules that cause cell death also elicit autophagy, a cytoprotective mechanism relying on the digestion of potentially harmful intracellular structures, notably mitochondria. When high doses of these agents are employed, cells undergo mitochondrial outer membrane permeabilization and die. In contrast, low doses of such cytotoxic agents can activate hormesis in several paradigms, and this may explain the lifespan-prolonging potential of autophagy inducers including resveratrol and caloric restriction."
"YET ANOTHER USELESS LIFESTYLE STUDY"
Friday, September 16, 2011
I am not unsympathetic to this viewpoint: recent research shows that "women should raise their glasses to a healthier old age, but we've heard it all before - and just the opposite. ... This is the conclusion of a study of 14,000 female nurses that started in 1976. The brainchild of the Harvard School of Public Health, Boston is the latest result from numerous studies of this nature that have produced all manner of contradictory results. ... In 1976, the [Framington study] is supposed to have shown a connection between menopause and the increased risk of heart disease, which is a bit like saying it found a connection between age and life expectancy - exactly what is one supposed to do with a datum like that? ... At the end of the day, one must ask what is the point of such studies, and specifically what is the point of a study that attempts to link the consumption of wine by women with longevity, especially when Marie Lloyd was telling us a little of what you fancy does you good way back in 1915? Rather than mounting expensive years' or decades' long studies as make-work schemes for medical scientists and their chums in Whitehall, Washington and elsewhere, the governments of the world might be better advised setting them to work to discover the actual causes of disease, and maybe to develop vaccines and other methods of combatting them, or better still, maybe they should follow in the footsteps of gerontologist Aubrey de Grey and his SENS organisation?"
BULLISH ON THE FUTURE OF THERAPIES BASED ON INDUCED PLURIPOTENT STEM CELLS
Thursday, September 15, 2011
Some enthusiasm from the research community: "induced pluripotent stem (IPS) cells [are] where I'm putting almost all of my chips these days, because it combines many of my interests - genomics, sequencing, epigenetics, synthetic biology, stem cells. I don't think people have fully appreciated how quickly adult stem cells and sequencing and synthetic biology have progressed. They have progressed by orders of magnitude since we got IPS. Before that, they basically weren't working. ... There is much to be worked out. But here's the leap. If you want to accelerate this, you have to pick an intermediate target that doesn't sound so scary. So you'll start out with bone marrow patients. And you're going to basically make a synthetic version of that patient's bone marrow using IPS, which is going to work much better than the diseased bone marrow. And once this works that's going to catch on like wildfire. And then you'll do skin, and then you'll do every other stem cell you can get. ... Will people who are, say, aging but not yet sick ever be able to use this technology? I don't consider this medicine, it's preventive. I expect somebody who is truly brave, who has nothing wrong with them other than maybe the usual aging, saying: 'I want a bone marrow transplant', or intestinal, or whatever. And it will gain momentum from there. ... Initially it will be wealthy people who will try this. Ironically, wealthy people are often willing to be the guinea pigs that are really in a sense the front line of new technologies. They're the foot soldiers. They're willing to put themselves at risk, and to spend money on it."
TRAINING THE IMMUNE SYSTEM TO DESTROY CANCER
Thursday, September 15, 2011
The New York Times is running a piece on a recent small trial of immune therapy for leukemia: "A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose. Doctors removed a billion of his T-cells - a type of white blood cell that fights viruses and tumors - and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig's veins. At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst. A few weeks later, the fevers were gone. And so was the leukemia. There was no trace of it anywhere - no leukemic cells in his blood or bone marrow, no more bulging lymph nodes on his CT scan. His doctors calculated that the treatment had killed off two pounds of cancer cells. A year later, Mr. Ludwig is still in complete remission. Before, there were days when he could barely get out of bed; now, he plays golf and does yard work."
AN INTERESTING RESULT FROM SIR2
Wednesday, September 14, 2011
Sir2 in yeast is one of the earliest discovered sirtuins, an important set of genes in the study of calorie restriction. Unfortunately that research has yet to generate a useful calorie restriction mimetic drug, and is looking less promising than it did initially. But here is an interesting result: "Activation of Sir2-orthologs is proposed to increase lifespan downstream of dietary restriction (DR). Here we describe an examination of the effect of 32 different lifespan-extending mutations and four methods of dietary restriction on replicative lifespan (RLS) in the short-lived sir2Δ yeast strain. In every case, deletion of SIR2 prevented RLS extension; however, RLS extension was restored when both SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not directly required for RLS extension. These findings indicate that suppression of the sir2Δ lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Δ cells senesce rapidly by a mechanism distinct from that of wild-type cells. They also demonstrate that failure to observe life span extension in a short-lived background, such as cells or animals lacking sirtuins, should be interpreted with caution." Things are, as ever, more complex than we'd like in other words. One of the reasons that sirtuins haven't led directly to calorie restriction mimetics is that they are only one small part in a larger mechanism, and possibly not even a critical part - just the one that was easiest to notice.
TOWARDS PRINTED ARTIFICIAL BLOOD VESSELS
Wednesday, September 14, 2011
Via ScienceDaily: researchers "are applying new techniques and materials to come up with artificial blood vessels [that] will be able to supply necessary nutrients to artificial tissue and maybe even complex organs in the future. ... It seemed practically impossible to build structures such as capillary vessels that are so small and complex, especially the branches and spaces in between. But production engineering came to the rescue because rapid prototyping makes it possible to build workpieces specifically according to any complex 3-D model. Now, scientists [are] working on transferring this technology to the generation of tiny biomaterial structures by combining two different techniques: the 3-D printing technology established in rapid prototyping and multiphoton polymerization developed in polymer science ... A 3-D inkjet printer can generate 3-dimensional solids from a wide variety of materials very quickly. It applies the material in layers of defined shape and these layers are chemically bonded by UV radiation. This already creates microstructures, but 3-D printing technology is still too imprecise for the fine structures of capillary vessels. This is why these researchers combine this technology with two-photon polymerization. Brief but intensive laser impulses impact the material and stimulate the molecules in a very small focus point so that crosslinking of the molecules occurs. The material becomes an elastic solid, due to the properties of the precursor molecules that have been adjusted by the chemists in the project team. In this way highly precise, elastic structures are built according to a 3-dimensional building plan."
AUTOPHAGY VERSUS ATHEROSCLEROSIS
Tuesday, September 13, 2011
An interesting view of one benefit of autophagy, a collection of housekeeping processes that are boosted by the practice of calorie restriction: researchers have "shown that autophagy, a pathway preserved during evolution, functions to engulf and digest cholesterol accumulated in artery walls. This process facilitates the removal of cholesterol and may provide an entirely new target to reverse atherosclerosis, the main cause of heart attack and stroke. Cholesterol accumulates in the walls of arteries leading to atherosclerosis, also known as narrowing of arteries and which causes blockages and reduces blood flow to the heart. This often culminates in heart attacks and strokes. The autophagy pathway, which means self-digestion, developed early in single-cell organisms to allow the clearance of accumulated dysfunctional molecules. ... The finding that autophagy also functions to digest and liberate cholesterol from cells and the fact that we know this pathway is regulated offers hope for the development of new drugs that could activate export of cholesterol from the walls of arteries."
ANOTHER EXAMPLE OF A TARGETED CANCER THERAPY
Tuesday, September 13, 2011
One approach to the next generation of cancer therapies is to use existing chemotherapy drugs coupled with cell-targeting mechanisms that deliver those drugs only to cancer cells: "A common chemotherapy drug has been successfully delivered to cancer cells inside tiny microparticles using a method inspired by our knowledge of how the human immune system works. The drug, delivered in this way, reduced ovarian cancer tumours in an animal model by 65 times more than using the standard method. This approach is now being developed for clinical use. ... It's like we've made a re-enactment of the battle of Troy but on the tiniest scale. In Troy, the Greeks fooled the Trojans into accepting a hollow horse full of soldiers - we've managed to trick cancer cells into accepting drug-filled microparticles. ... by coating tiny microparticles of around a hundredth the diameter of a human hair with a special protein called CD95, [researchers] could in fact trigger cancer cells into ingesting these particles. Not only that, but the particles could deliver a dose of a common chemotherapy drug called paclitaxel. The key to their success is that CD95 attaches to another protein called CD95L, which is found much more commonly on the surface of cancer cells than it is on normal healthy cells. Once attached, the cancer cells ingest CD95 and the microparticle with it. Inside the cell, the microparticle can unload its chemotherapy cargo, which kills the cell to reduce the size of the tumour."
Monday, September 12, 2011
At Discover Magazine: "The Postmortal is not about a post-mortal society, it is about a post-aging society. Lots and lots and lots of people die in Magary's vision. In fact, he seems to argue that in the absence of death, people will not only seek death but will create circumstances that create death and thereby, create meaning. It is only when Farrell's life is most in peril that he finds purpose in existence. But Farrell is never immortal, no one is. So my question is: is the process of aging as meaningful as the condition of being mortal? This question vexed me, because I know a great many people who have aged with grace. They wear wizened white beards or crinkled smiles that highlight eyes behind inch-thick spectacles. Some people are just awesome at being old. They have custom canes and smoke ivory pipes and say saucy things that only they can get away with. To reference Harry Potter again, Voldemort, Mr.Flees-From-Death himself, is contrasted with Albus Dumbledore and Minerva McGonagall, both of whom are walking idealizations of what the aging process should look like. But that's just it, isn't it? They are idealizations. Reality presents a grimmer picture. Alzheimer's, Parkinson's, and a laundry list of other late-onset diseases savage the body just enough that modern medicine can step in to keep the heart beating and the organs limping along while the mind deteriorates to the point of nothingness. Aging in the modern era is about slow unstoppable loss - of hearing, of memory, of mobility, of continence, of dignity. What part of that process creates meaning in our lives? ... In Magary's mind, the stop of physical aging is the stop of maturation. In this sense, I suspect Magary's indictment is not of those like Aubrey de Grey who seek the end of aging, but of those who resist maturation. Magary's values are essentially conservative. ... Human beings do not settle down because they age anymore than people have quarter-life or midlife or three-quarter life crises because they age. People are content or discontent based on the life they are currently living."
COGNITIVE IMPAIRMENT CORRELATES WITH MORTALITY
Monday, September 12, 2011
Aging is damage, and therefore we should not be surprised to see that people with more obvious signs of damage are more likely to die sooner: "According to a new, long-term [study], cognitive impairment, especially at the moderate to severe stages has an impact on life expectancy similar to chronic conditions such as diabetes or chronic heart failure. Nearly 4,000 people between the ages of 60 to 102 years, initially seen from 1991 to 1993 by primary care physicians at Wishard Health Services, a large public hospital with community health centers in Indianapolis, participated in the study. The patients were followed for 13 years. ... Previous studies have associated cognitive impairment with an increased risk for death, but most of this work focused on patients with Alzheimer disease and subjects in research centers. The patients in our study better reflect the general public, displaying no indications of disease or mild, moderate or severe cognitive impairment. We found that even mild cognitive impairment, as determined by a simple screening tool in a primary care physician's office, has a strong impact on how long individuals survive on the same order as other chronic diseases." Cognitive impairment springs from physical causes linked to general health and the pace at which aging progresses in an individual, such as the state of blood vessels in the brain, for example. More damage at the level of cells and molecules leads to more evident dysfunction that we can see with our own eyes.