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BGRF Newsletter 9th June 2008 Jump to: Announcements; Leading Articles; Digest: science, general
9th June: Biogerontology Research Foundation Registered as a UK Charity Formally announced on 9th june, the BGRF was registered as UK Charity 1124054 on 14th May. Full details in the press release. 30th May: Alex Zhavoronkov Voted as BGRF Trustee The original trustees of the BGRF are delighted that Alex accepted their invitation to join them. Alex is the head fundraiser of the BGRF, and shares the rest of the team's passion about fighting the diseases of ageing.
Calorie Restricted Diet and Longevity Calorie Restriction (CR) is a diet in which calorie intake is reduced, as compared to diets that do not limit consumption. Calorie Restriction with Optimum Nutrition (CRON), also called the Longevity Diet, has the potential to increase the average and maximum life span. CR is best characterized as undernutrition without malnutrition. Optimum Nutrition consists of eating the right amounts of nutrients on a proper schedule to achieve the best performance and the longest possible lifetime in good health. This theory of the life-extending effect of reduced-calorie diets was reported in first 1935. It has been proved true for many species including yeasts, worms, mice and rats. Many mechanisms have been proposed to try to explain why CR increases life span, though as yet there is no clear consensus. Researchers have not been able to determine if humans on calorie restricted diets will live longer, but preliminary observations of the physiological changes caused by CR indicate that life-extending effects will probably be observable in humans also. A test conducted on the genes of baker’s yeast combined with a low-calorie diet has resulted in increasing the lifespan of the yeast by a factor of 10. Valter Lango and his team from the University of Southern California, Los Angeles, created a strain of yeast that lacks the genes RAS2 and SCH9. These genes are linked with ageing in yeast, and have been implicated in cancer in humans. Research was conducted to increase the lifespan of the yeast by keeping it on a calorie-restricted diet. The results led to extended life of the yeast from one to ten weeks, and without any evident side effects. Similar research conducted by Sinclair's lab reportedly found small molecules (e.g. resveratrol) that activate Sir2/SIRT1 and extend the lifespan of yeast, nematode worms, fruit flies, and mice consuming a high caloric diet. Previous studies indicate that calorie restriction increases the lifespan of mammals and this technique is now being tried on mice. However, mutations associated with longevity often cause problems. A study is also being conducted on the people of Ecuador whose natural genetic mutations are similar to those of long-lived yeast. Sources: http://www.scientificpsychic.com/health/crondiet.html http://www.newscientist.com/article/mg19726404.700-scientists-find-fountain-of-youth--for-yeast.html Premature Ageing: After-Effects of Cigarette Smoking Modern gene research has reaffirmed the truth in the timeless saying; cigarette smoking is injurious to health. Latest research shows that smoking disables a gene, SIRT1 (Silent Mating Type Information Regulation 2 homolog 1), present in the lungs. SIRT1 helps control premature ageing by reducing stress, cell death, and destructive inflammation of the lungs. Without the protection provided by SIRT1 the lungs become susceptible to chronic obstructive pulmonary disease (COPD) and lung cancer. Environmental stress such as cigarette smoke or pollution decreases production of surtuin 1 in the lungs. Irfan Rahman, Professor of Environmental Medicine, University of Rochester, says, “This novel protein will allow us to program our body's immune-inflammatory system against lung damage and premature aging. The hallmark of this discovery is that we may be able to provide remedies to millions of smokers who would like to quit but cannot kick their addiction, and millions of former smokers who, despite quitting, remain at risk for illness as they age." Professor Rahman has spent years studying the 4700 toxic chemical compounds found in cigarettes damaging the lung tissue. Professor Rahman’s team along with Vuokko L. Kinnula, M.D., at Helsinki University Hospital in Finland, studied the levels of SIRT1 in the lungs of nonsmokers and smokers with and without COPD. Thirty-seven patients from Helsinki, who were undergoing either a lung resection for suspected cancer or a lung transplant, volunteered to provide tissue samples for the study. Researchers confirmed that the activity of SIRT1 was significantly lower in smokers who had COPD and in smokers who did not have disease, compared to nonsmokers. Scientists are also hoping to find ways to reverse the lung damage. Source: http://www.cbc.ca/health/story/2008/01/24/smoking.html Aging with poise by scrapping the scrap Autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more essential processes. Scientists at the Salk Institute for Biological Studies reported that “Boosting autophagy in the nervous system of fruit flies prevented the age-dependent accumulation of cellular damage in neurons and promoted longevity.” The age-related accumulation of proteins and lipids damaged by chemically aggressive forms of oxygen is considered by most in the geriatrics field to be a normal part of the aging process. Consequently, in most age-associated diseases, such as Alzheimer's, damaged proteins accumulate in excessive amounts, which leads to progressive cell death in the brain. All cells undergo autophagy – literally self-eating – which requires the assembly of specialized vesicles called autophagosomes. These vesicles surround or engulf damaged cellular proteins or structures and then traffic the "bagged garbage" to a second group of vesicles, which disposes off the trash with the help of digestive enzymes. This process can be enhanced when animals are placed on a calorie-restricted diet, a regime known to extend lifespan. "The activation of autophagy facilitates the removal of damaged molecules that accumulate during cellular aging," says Finley from the Salk Institute. "This may be particularly important in the nervous system since neurons produce damaged molecules at a much higher rate than most cell types." Keeping cells free of damaged molecules is critical for neurons because unlike many cells, they do not divide or replace themselves once created at birth. "They rely on autophagy together with other clearance and detoxification pathways to keep themselves healthy and functioning for decades," explains Finley. Studies by the Salk researchers on the fruit fly Drosophila indicated that the expression of several autophagy genes decreased over the normal lifespan of fruit flies. The Salk researchers mainly focused on one particular protein, Atg8a (an essential component for the formation of new autophagosomes). The levels of Atg8a were significantly reduced by four weeks of age, a time when the flies are considered middle aged. At the same time, protein aggregates were not efficiently cleared by the cellular clean-up crew and started to accumulate. Without Atg8a, damaged proteins marked for degradation started accumulating early and life expectancy dropped. "The abnormal accumulation of protein aggregates had striking similarities to those seen in the most common human neurodegenerative diseases," says first author Anne Simonsen, Ph.D., a visiting scientist from the University of Oslo, Norway. With the increase in the neuronal levels of Atg8a prevented the accumulation of protein aggregates and extended the average lifespan. "Our experiments show for the first time genetically that autophagy can sequester and eliminate misfolded and damaged proteins, which accumulate in neurons as normal part of the aging process," says Simonsen, "but most importantly they demonstrate that enhancing the clearance of damaged proteins and protein aggregates increases longevity." Source: http://www.salk.edu/news/news_press_details.php?id=192
Another Way Your Aging Immune System Harms You (May 23 2008) http://pmid.us/18495785 An interesting paper: "Recent studies suggest that activation of the peripheral immune system elicits a discordant central (i.e., in the brain) inflammatory response in aged but otherwise healthy subjects compared with younger cohorts. A fundamental difference in the reactive state of microglial cells in the aged brain has been suggested as the basis for this discordant inflammatory response. Thus, the aging process appears to serve as a 'priming' stimulus for microglia, and upon secondary stimulation with a triggering stimulus (i.e., peripheral signals communicating infection), these primed microglia release excessive quantities of proinflammatory cytokines. ... there is a propensity for this response to be maladaptive in aged subjects, resulting in greater severity and duration of the sickness behavior syndrome." Your immune system evolved for a life span of a few decades, optimized to help you live long enough to pass on genes. It's all downhill after that, as some of those optimizations start to be actively harmful later on in life. Repairing these deficiencies in the aging immune system is an important component for extending healthspan. Upgrading Cells With Artificial Organelles (May 23 2008) http://technology.newscientist.com/article/dn13967-cell-organs-get-plastic-upgrades.html If you can build artificial cells, why not build artificial organelles within natural cells? From the New Scientist, a look at the future: "Human cells could have their metabolisms upgraded without altering their genes by inserting tiny plastic packages of enzymes ... [researchers] coated their polymer vesicles in a chemical that encouraged human white blood cells called macrophages to engulf them. The small capsules contained enzymes, just like natural organelles. The enzymes chosen produced fluorescent chemicals, signalling they were working without problems inside their new host. ... Artificial organelles might also be able to treat conditions caused by a deficit of a particular enzyme. For example, someone with lactose intolerance could have their digestive cells given artificial organelles containing lactose-digesting enzymes. In the far future, it might be possible to introduce non-human metabolic functions into human cells. ... We could, in principle, bring in a nanoreactor that [lets] your skin do something like photosynthesis. So if you are hungry, you just lie in the sun." Flights of fancy aside, it is easy to imagine many other, more directly beneficial, applications of this technology: for example, enzymes to degrade damaging aggregates that accumulate with age. Essays From the Aging 2008 Event at UCLA http://www.fightaging.org/archives/001487.php "The difference between us and cars is that we know everything there is to know about repairing cars. Just as a Ferrari would have been impossibly complex to build two hundred years ago, so is the body today. The difference is that biology is quickly becoming an information science. As loyal readers of this column know, information technologies increase at an exponential rate. Just like computers, biotechnology such as DNA sequencing or fMRI imaging roughly doubles in capability every year. We will soon be able to deal with the nanoscale devices that make up the human machine and fix the damage that occur to them." http://www.fightaging.org/archives/001486.php "Age-defying creams and lotions, esoteric herbs and elixirs, botox and plastic surgery, what do they all have in common? None of them will actually increase your lifespan. Usually, they're snake oil. At best, they improve external appearance without actually extending life. We deserve better, and we'll need it if we want to live longer than the typical four score and ten years." Understanding Embryonic Stem Cells (May 22 2008) http://www.sciencedaily.com/releases/2008/05/080521131538.htm ScienceDaily notes new knowledge that will lead to greater and more effective control over totipotent stem cells: "Our study suggests that what we believe about how embryonic stem cell self-renewal is controlled is wrong. Our findings will likely change the research direction of many stem cell laboratories. ... Contrary to the current understanding of stem cell self-renewal and differentiation, the findings suggest that embryonic stem cells will remain undifferentiated if they are shielded from differentiation signals. By applying small molecules that block the chemicals from activating the differentiation process, the natural default of the cell is to self-renew, or multiply, as generic stem cells. ... This study presents a completely new paradigm for understanding how to grow embryonic stem cells in the laboratory. The discovery has major implications for large scale production of specialized cells, such as brain, heart muscle and insulin producing cells, for future therapeutic use." Replacing cells lost to aging is one important part of any suite of healthspan-extension therapies, and advances that bring that goal closer are welcome. Improving Gene Therapy Thirtyfold (May 21 2008) http://www.sciencedaily.com/releases/2008/05/080520090529.htm When watching progress in medical science, you have to keep your eye on developments away from the headlines, such as improvements in infrastructure and methodology. It is progress at that level that enables the later big, bright advances that capture all the attention. Here's an example from ScienceDaily: "geneticists say they have developed a new version of the adeno-associated virus used in gene therapy that works about 30 times more efficiently in mice than vectors scientists currently rely on ... Based on our studies and those of others, it's become clear that the reason you need so much is because about half the [adeno-associated virus (AAV)] particles get stuck in the cytoplasm. It doesn't get to the nucleus very efficiently. The reason for that is obvious. AAV is seen by the body as an invading protein and it tries to block it ... We didn't change anything except the amino acid that does not allow phosphorylation to occur ... We were very surprised. It's amazing to think that changing one amino acid could produce these results." Gene therapy is a very important tool, and order-of-magnitude improvements in cost and efficiency here will ripple out through the cutting edge of medical research - including many areas important to the longevity medicine of tomorrow. Growing Body Parts In the Laboratory (May 20 2008) http://www.redorbit.com/news/health/1390940/growing_body_parts_in_the_lab_becomes_reality/ RedOrbit looks at tissue engineering: "Other alternatives to organ transplants have proved elusive. Transplants from animals, for example, face serious risks of rejection or viral infections. And mechanical organs, such as heart pumps, have been only a temporary solution. ... If we want to live forever, we need to do better ... Engineering body parts - tissues and whole organs that are genetically compatible and available on demand - sounds like science fiction. But researchers at medical centers around the world are working to make it a reality. Already, a handful of children with spina bifida have received new bladders. Replacement blood vessels are being tested on dialysis patients. And researchers have re-created a beating rat heart. ... [The] first wave of tissue engineering did yield some useful products, such as artificial skin grafts that are used to treat diabetic skin ulcers. But many of the awe-inspiring breakthroughs that scientists are talking about are still many years away ... The real potential for tissue engineering is the vital organs, but we're a ways away from that, even though there's some exciting things being done." The article looks at some of the more recent advances in engineering blood vessels, building complete hearts using a novel scaffold method, and of work on tissue engineered bladders. More Progress Towards Alzheimer's Vaccines (May 19 2008) http://www.eurekalert.org/pub_releases/2008-05/uorm-vti051908.php EurekAlert! reports on another promising Alzheimer's vaccine in the works: "Vaccinated mice generated an immune response to the protein known as amyloid-beta peptide, which accumulates in what are called 'amyloid plaques' in brains of people with Alzheimer's. The vaccinated mice demonstrated normal learning skills and functioning memory in spite of being genetically designed to develop an aggressive form of the disease. ... vaccinated mice not only performed better, we found no evidence of signature amyloid plaque in their brains ... The mice [also] harbored a mutation that causes the tau-related tangle pathology ... What we found exciting was that by targeting one pathology of Alzheimer's - amyloid beta - we were able to also prevent the transition of tau from its normal form to a form found in the disease state ... due to the number of studies required to satisfy regulatory requirements, it could be three or more years before human trials testing this type of Alzheimer's vaccine occur."
UK Dementia Costs Set to Soar A recent report by the Kings Fund, a heathcare charity and think-tank, has quantified the expected rise in costs due to age-related dementia. Around 50% of people in their eighties experiences dementia, and the report predicts that as the baby-boom generation reaches this age in the new few decades costs for their care will rise to a staggering £47 billion annually. This is potentially an unsustainable load on the public finances, and will be mirrored across the world. This is another illustration of just why the BGRF and others' focus on healthspan extension is so vital, in additon to the humanist arguments of reducing suffering. Pension Industry Forsees Rising Life Expectancy http://news.bbc.co.uk/2/hi/business/7413120.stm The pension, insurance and actuarial sectors tend to be conservative in their outlook, but they stand to mimimise their future exposure by producing the best possible predictions on life expectancy. Here's an update from the BBC on a few of the changes that have been taking place in the past few years: "Many UK companies are now assuming their male pensioners will live, on average, one year longer than they assumed in 2006. ... It's interesting they are going by one year, every year. There is an element of catch-up but there is great uncertainty about how this trend will go in the future." The uncertainty is further fuelled by the tremendous promise offered by current research programmes. |
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