FIGHT AGING! NEWSLETTER
November 26th 2012
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!
- Increased Longevity in Mice by Removing Cardiotrophin 1
- Some Answers in Aging Science are Not Worth the Effort
- Removing Large and Unnecessary Costs Imposed Upon Medicine
- Insufficiently Terrified of Aging or Too Terrified of Aging?
- Latest Headlines from Fight Aging!
- Vacuole Changes as a Contributing Cause of Yeast Cell Aging
- Improvements in Printed Cartilage Scaffolds
- Towards an Understanding of Why Dopamine Neurons Are Vulnerable in Parkinson's Disease
- Looking at Immune Function in Long-Lived Clk1 Mutant Mice
- Treating Spine Injury in Dogs via Stem Cell Transplant
- Telomere Length and Life Expectancy in Warblers
- Aging is Global, So Expect Correlations
- An Example of Stem Cell Researchers Tackling Aging
- Astrocytes as a Potential Target for Alzheimer's Therapies
- Intuition, Mortality Rate, and Life Expectancy
INCREASED LONGEVITY IN MICE BY REMOVING CARDIOTROPHIN 1
Here is an question to think on while you recover from the excesses of the recent holiday: should we expect there to be, in humans, mice, or other species, many simple genetic alterations that are unambiguously beneficial for the individual, yet which evolution did not select for? Another way of looking at this question: why is it that there exist a range of ways to engineer slightly-genetically-altered mice that are stronger, healthier, and longer-lived than the standard wild variants?
The classical answer to this question suggests that these improvements come with fitness costs in the wild, or - more subtly - have the effect of dramatically reducing ability to survive under some rare combination of environmental circumstances. This is obviously the case when you look at mice lacking growth hormone, which live 60-70% longer than their peers, but are absolutely unfit for life in the wild due to their small size and, more importantly, issues with maintaining body temperature due to that small size. But for unambiguously all-round beneficial mutations like myostatin knockout, one has to think harder about how this could be a disadvantage.
Here is another example of a mutation that everyone would want for their offspring, should it turn out to work much the same way in humans: the absence of CT-1 is associated with decreased arterial fibrosis, stiffness, and senescence and increased longevity in mice likely through downregulating apoptotic, senescence, and inflammatory pathways. CT-1 may be a major regulator of arterial stiffness with a major impact on the aging process. ... CT-1-null mice displayed a 5-month increased median longevity compared with wild-type mice.
I look forward to the day on which one can take a flight across the Pacific as a medical tourist, drop into a reputable clinic, and have a few genetic alterations done: myostatin, cardiotrophin 1, and others that arise and are shown to have no downsides for people living in a society with access to modern medicine.
SOME ANSWERS IN AGING SCIENCE ARE NOT WORTH THE EFFORT
Considerations of cost versus benefit drive all human action. With this in mind, and when considering the field of aging research, I'd contend that a fair number of the better defined lines of research are not worth the time and resources likely required to reach definitive results. By better defined I mean here research that can be expressed as a concise and narrow question (e.g. "why are naked mole-rats immune to cancer?") rather than research that is as much about finding the questions in the first place (e.g. attempting to establish a coherent big picture in the progression of Alzheimer's disease), or about gathering data for later use in other people's attempts to answer questions (e.g. whole genome sequencing of various species).
The well-known difference in longevity between human genders is a good example of a constrained and defined question in aging research: why do women live longer than men? It is also, to my mind, a great example of a question with an answer that isn't worth the cost involved in obtaining it. Research to date reveals this to be an inordinately complex issue, possessing all the signs of requiring a great deal of time and money to make any headway towards definitive answers. That is the cost side of the cost-benefit consideration. On the benefit side, we might think that the best possible benefit resulting from a definitive answer to the question "why do women life longer than men?" is something like five to seven years of life - that being the additional life expectancy enjoyed by women in wealthier regions of the world, and which might conceivably be captured by men given an exact methodology to do so. Which is not to say that this outcome could be engineered as a practical matter even if the cause of the difference was known in certainty - for example if it turns out to be, say, some many-headed web of fundamental interactions between metabolism and the genetics of being male, something that must be worked around rather than just altered.
Trying to safely alter metabolism with minimal side-effects is a complex and expensive business, a realm akin to traditional drug discovery processes, where billions can be spent with ease while only marginal benefits resulting. When it comes to slowing aging via metabolic and genetic manipulation, working through this drug discovery process, the mainstream research community believes there is little hope for significant progress towards longer human lives in the next few decades.
My point here is that a goal wherein the research community has no great hope of rapid progress, and which has every sign of being enormously expensive to pursue, and which can only at best somewhat point the way towards a possible gain of up to five years or so of healthy life in half the population is not a goal that merits a full-court press and singular attention - or at least not where better alternatives exist. Insofar as human aging goes, there is no shortage of better alternatives at this point. The aging research community should look to bolder plans, better and more beneficial ways to spend their time: work with far bigger potential gains. This is an age of revolution in the capabilities of biotechnology, a time for great leaps ahead in intervening in the aging process, not a time to be tinkering in the sandbox of fiddling questions.
REMOVING LARGE AND UNNECESSARY COSTS IMPOSED UPON MEDICINE
Insofar as politics goes, I'm against it. Both in the sense of a support for market anarchism as a desirable form of society and in the sense that what we see in the political sphere of our increasingly centralized societies today is reprehensible and destructive. There is control for the sake of control, ever-greater burdens imposed on builders of new technology, and progress in medicine is slowed for the personal aggrandizement of bureaucrats and those who line their pockets. When power accumulates to any group in society, and that group stands unopposed by peers, then it inevitably becomes corrupt.
The cartel of modern politics as practiced in countries like the US is the source of large and unnecessary costs put upon progress in medical technology - and this is a big problem for those of us who want to live longer, healthier lives. We stand at the dawn of an age in which aging might be treated as a medical condition, in which therapies could be designed to slow or reverse aging. But medicine and medical research labor beneath heavy regulation: the modern guilds like the AMA that seek to reduce supply; the agencies like the FDA that have few incentives to approve new medicines, yet seek ever-greater authority over all forms of treatment; the regulation and nationalization of medical services and insurance that severs customers from prices, and replaces markets with central planning after the Soviet model.
From a practical standpoint people of my views, being a minority, can do little but think of the vast benefits that might be realized should the present political costs imposed on progress in medicine suddenly evaporate. There are few opportunities to do more than that - we paw at the glass and stare longingly at the products on the other side, as it were. Human societies follow certain paths, and most lead away from individual freedoms of the sort needed for rapid progress in technology. Sad but true.
We can see a modest fraction of what might be achieved by stripping away regulation, guilds, and central planning by comparing progress in medicine over the past twenty years with progress in computing and software. Consider what computers and their role in everyday life would look like if it had always been the case that introducing a new machine or new software package meant spending years and $100 million to pass a bureaucratic one-size-fits-all process - and where radical new designs required a decade of expensive lobbying to be added to the list of what is permitted.
Yet this is exactly where things stand with medicine, at a time in which it is more important than it has ever been for progress to occur as rapidly as possible. A hundred thousand lives are lost every day to degenerative aging, and we might do something about that in the years ahead - but the therapies will emerge far more slowly than they would in a society that was more free and open than ours.
INSUFFICIENTLY TERRIFIED OF AGING OR TOO TERRIFIED OF AGING?
It is my hope that, if asked, most people would agree that degenerative aging is not a pleasant, beneficial thing to look forward to. It is a looming years-long tunnel of varying forms of increasing suffering, expense, loss of dignity, and disability. You wouldn't volunteer for the consequences of aging if they were optional. Everyone knows what's coming. Everyone gets a close-up preview of what will happen, in all its painful details via family, media, stories, the common currencies of education. No adult is truly ignorant of where aging leads and what its costs are.
Any yet, and yet. The masses carry on and for the most part put all thoughts of future suffering to one side - even as the young interact with old people day in and day out, and even as those old people live out their lives. The folk who look at degenerative aging and suggest, seriously, with reference to sound science, that perhaps we can and should do something about it are in a tiny minority. Further, they are often castigated for that view, as if it is something that shouldn't be brought out in polite company.
Living in fear of being dead is of debatable rationality, but living in fear of chronic pain and suffering seems eminently rational to me. You'd be terrified if a random thug could credibly threaten you with half the physical harm that aging is capable of. Fear is a great motivator, but unfortunately far from reliable in what it motivates people to do: the various shadings of fear are well characterized by a loss of analysis and control.
So people blithely walk towards degenerative aging and its suffering, and the vast majority choose to do nothing to try to fight against that future. Is that because they have too little fear of what lies ahead, or because they are too terrified to even bring out the topic for introspection, debate, and planning?
I have become perhaps one of the least qualified people to answer that sort of question. I am so far removed from the years in which I didn't think much on the topic, or had only ordinary thoughts about aging, that I have no insight left into what it was like or why I thought that way. The more I learn about rejuvenation biotechnology and the longer I spend observing the world while favoring the defeat of aging, the less I understand prevalent attitudes, and the more of a mystery it all becomes: the concurrent acknowledgement and aversion of degenerative aging; the existence of a vibrant "anti-aging" marketplace next to a lack of support for real longevity science; the signs of fear next to the signs of complacency.
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!
VACUOLE CHANGES AS A CONTRIBUTING CAUSE OF YEAST CELL AGING
Friday, November 23, 2012
The type of vacuole found in yeast cells is somewhat analogous to the lysosome that we animals possess in that it is involved in breaking down waste products and recycling broken cellular components (via the process of autophagy) that would otherwise harm the cell. It is an agent of cellular housekeeping, in other words. There the similarities end, however, as the vacuole performs many other vital tasks that the more specialized lysosome does not. So here, researchers show that they can extend life in yeast by reversing a change that occurs in the vacuole. Because the vacuole has many more tasks than the lysosome, it's not immediately clear that this has any application to our biology of aging, however. It is still worth keeping an eye on this research as we know that decline in lysosomal function (and thus of cellular housekeeping) is important in animal aging. You might recall, for example, that researchers managed to reverse the age-related loss of liver function in mice by finding a way to keep lysosomal function running at youthful rates. Similarly, reversing the root causes of lysosomal decline is on the SENS agenda - to be achieved by breaking down the build up of metabolic waste products that accumulate in lysosomes and cause them to malfunction. "Normally, mitochondria [in yeast] are beautiful, long tubes, but as cells get older, the mitochondria become fragmented and chunky. The changes in shape seen in aging yeast cells are also observed in certain human cells, such as neurons and pancreatic cells, and those changes have been associated with a number of age-related diseases in humans. The vacuole - and its counterpart in humans and other organisms, the lysosome - has two main jobs: degrading proteins and storing molecular building blocks for the cell. To perform those jobs, the interior of the vacuole must be highly acidic. [Researchers] found that the vacuole becomes less acidic relatively early in the yeast cell's lifespan and, critically, that the drop in acidity hinders the vacuole's ability to store certain nutrients. This, in turn, disrupts the mitochondria's energy source, causing them to break down. Conversely, when [researchers] prevented the drop in vacuolar acidity, the mitochondria's function and shape were preserved and the yeast cells lived longer. Until now, the vacuole's role in breaking down proteins was thought to be of primary importance. We were surprised to learn it was the storage function, not protein degradation, that appears to cause mitochondrial dysfunction in aging yeast cells. ... The unexpected discovery prompted [the researchers] to investigate the effects of calorie restriction, which is known to extend the lifespan of yeast, worms, flies and mammals, on vacuolar acidity. They found that calorie restriction - that is, limiting the raw material cells need - delays aging at least in part by boosting the acidity of the vacuole."
IMPROVEMENTS IN PRINTED CARTILAGE SCAFFOLDS
Friday, November 23, 2012
Cartilage is a deceptively complex tissue to build, due to the small-scale structure that determines its mechanical and load-bearing properties - getting that structure right has proven to be a challenge. Researchers have nonetheless been making progress towards this goal in recent years, and the lessons learned will be carried forward to other tissue engineering projects: "The printing of three-dimensional tissue has taken a major step forward with the creation of a novel hybrid printer that simplifies the process of creating implantable cartilage. [The] printer is a combination of two low-cost fabrication techniques: a traditional ink jet printer and an electrospinning machine. In this study, the hybrid system produced cartilage constructs with increased mechanical stability compared to those created by an ink jet printer using gel material alone. The constructs were also shown to maintain their functional characteristics in the laboratory and a real-life system. The key to this was the use of the electrospinning machine, which uses an electrical current to generate very fine fibres from a polymer solution. Electrospinning allows the composition of polymers to be easily controlled and therefore produces porous structures that encourage cells to integrate into surrounding tissue. The constructs [were] inserted into mice for two, four and eight weeks to see how they performed in a real life system. After eight weeks of implantation, the constructs appeared to have developed the structures and properties that are typical of elastic cartilage, demonstrating their potential for insertion into a patient."
TOWARDS AN UNDERSTANDING OF WHY DOPAMINE NEURONS ARE VULNERABLE IN PARKINSON'S DISEASE
Thursday, November 22, 2012
The most visible signs of Parkinson's disease are caused by the progressive destruction of a comparatively small population of dopamine-generating neurons in the brain. But why these cells? A full answer to that question might lead to ways to block progression of the condition: "Neuroinflammation and its mediators have recently been proposed to contribute to neuronal loss in Parkinson's, but how these factors could preferentially damage dopaminergic neurons has remained unclear until now. [Researchers] were looking for biological pathways that could connect the immune system's inflammatory response to the damage seen in dopaminergic neurons. After searching human genomics databases, the team's attention was caught by a gene encoding a protein known as interleukin-13 receptor alpha 1 chain (IL-13Ra1), as it is located in the PARK12 locus, which has been linked to Parkinson's. IL-13rα1 is a receptor chain mediating the action of interleukin 13 (IL-13) and interleukin 4 (IL-4), two cytokines investigated for their role as mediators of allergic reactions and for their anti-inflammatory action. With further study, the researchers made the startling discovery that in the mouse brain, IL-13Ra1 is found only on the surface of dopaminergic neurons. "This was a 'Wow!' moment." The scientists set up long-term experiments using a mouse model in which chronic peripheral inflammation causes both neuroinflammation and loss of dopaminergic neurons similar to that seen in Parkinson's disease. The team looked at mice having or lacking IL-13Ra1 and then compared the number of dopaminergic neurons in the brain region of interest. The researchers expected that knocking out the IL-13 receptor would increase inflammation and cause neuronal loss to get even worse. Instead, neurons got better. If further research confirms the IL-13 receptor acts in a similar way in human dopaminergic neurons as in mice, the discovery could pave the way to addressing the underlying cause of Parkinson's disease. Researchers might, for instance, find that drugs that block IL-13 receptors are useful in preventing loss of dopaminergic cells during neuroinflammation."
LOOKING AT IMMUNE FUNCTION IN LONG-LIVED CLK1 MUTANT MICE
Thursday, November 22, 2012
Reducing expression of clk1 (known as Mclk1 in mice) is one of the few known single-gene alterations that can slow aging enough to extend life in mice by as much as 30%. First impressions were that it works by altering mitochondrial function - and regular readers will know by now that mitochondria and the the pace of their self-inflicted damage is very important in aging and longevity. There is some debate as to how exactly this works in the case of clk-1, however, as the way in which it changes metabolic processes isn't self-evidently beneficial given what is known today. A fair amount of wading through complexity to gain a better understanding of mammalian biochemistry still needs to happen. Few single gene alterations change only one thing, and clk-1 reduction has all sorts of other knock-on effects in metabolism and biological systems. Researchers here are working their way through what it does to the immune system, and how that might be beneficial even though it doesn't at first look that way: "The immune response is essential for survival by destroying microorganisms and pre-cancerous cells. However, inflammation, one aspect of this response, can result in short- and long-term deleterious side-effects. Mclk1+/− mutant mice can be long-lived despite displaying a hair-trigger inflammatory response and chronically activated macrophages as a result of high mitochondrial [reactive oxygen species] generation. Here we ask whether this phenotype is beneficial or simply tolerated. We used models of infection [and] found that Mclk1+/− mutants mount a stronger immune response, control bacterial proliferation better, and are resistant to cell and tissue damage resulting from the response, including fibrosis and types of oxidative damage that are considered to be biomarkers of aging. Moreover, these same types of tissue damage were found to be low in untreated 23 months-old mutants. ... Mclk1+/− mutants thus display an association of an enhanced immune response with partial protection from age-dependent processes and from pathologies similar to those that are found with increased frequency during the aging process. This suggests that the immune phenotype of these mutants might contribute to their longevity. We discuss how these findings suggest a broader view of how the immune response might impact the aging process."
TREATING SPINE INJURY IN DOGS VIA STEM CELL TRANSPLANT
Wednesday, November 21, 2012
A pleasant example of what can sometimes be achieved with even comparatively crude autologous stem cell therapies: "Scientists have reversed paralysis in dogs after injecting them with cells grown from the lining of their nose. The pets had all suffered spinal injuries which prevented them from using their back legs. The [team] is cautiously optimistic the technique could eventually have a role in the treatment of human patients. The study is the first to test the transplant in "real-life" injuries rather than laboratory animals. [The] dogs had olfactory ensheathing cells from the lining of their nose removed. These were grown and expanded for several weeks in the laboratory. Of 34 pet dogs on the proof of concept trial, 23 had the cells transplanted into the injury site - the rest were injected with a neutral fluid. Many of the dogs that received the transplant showed considerable improvement and were able to walk on a treadmill with the support of a harness. None of the control group regained use of its back legs. The researchers say the transplanted cells regenerated nerve fibres across the damaged region of the spinal cord. This enabled the dogs to regain the use of their back legs and coordinate movement with their front limbs. The new nerve connections did not occur over the long distances required to connect the brain to the spinal cord. [In] humans this would be vital for spinal injury patients who had lost sexual function and bowel and bladder control. ... This is not a cure for spinal cord injury in humans - that could still be a long way off. But this is the most encouraging advance for some years and is a significant step on the road towards it."
TELOMERE LENGTH AND LIFE EXPECTANCY IN WARBLERS
Wednesday, November 21, 2012
Researchers are making better progress of late in finding ways to use changes in telomere length that occur with aging as a marker for biological age and life expectancy - though it remains an open question as to whether telomere shortening is a cause of aging versus a secondary consequence of causes of aging. You might look at work in mice published earlier this month, for example. Or moving to birds, a few years back researchers noted that pace of telomere shortening over time correlated with lifespan differences between species. Here researchers consider telomere length in a species of warbler: "[Researchers] studied the length of chromosome caps - known as telomeres - in a 320-strong wild population of Seychelles Warblers on a small isolated island. ... Over time these telomeres get broken down and become shorter. When they reach a critical short length they cause the cells they are in to stop functioning. This mechanism has evolved to prevent cells replicating out of control - becoming cancerous. However the flip side is that as these zombie cells build up in our organs it leads to their degeneration - aging - and consequently to health issues and eventually death. Telomeres help safeguard us from cancer but result in our aging. We wanted to understand what happens over an entire lifetime, so the Seychelles Warbler is an ideal research subject. They are naturally confined to an isolated tropical island, without any predators, so we can follow individuals throughout their lives, right through to old age. We investigated whether, at any given age, their telomere lengths could predict imminent death. We found that short and rapidly shortening telomeres were a good indication that the bird would die within a year. We also found that individuals with longer telomeres had longer life spans overall. It used to be thought that telomere shortening occurred at a constant rate in individuals, and that telomere length could act as an internal clock to measure the chronological age of organisms in the wild. However while telomeres do shorten with chronological age, the rate at which this happens differs between individuals of the same age. This is because individuals experience different amounts of biological stress due to the challenges and exertions they face in life. Telomere length can be used as a measure of the amount of damage an individual has accumulated over its life. We saw that telomere length is a better indicator of life expectancy than chronological age - so by measuring telomere length we have a way of estimating the biological age of an individual - how much of its life it has used up."
AGING IS GLOBAL, SO EXPECT CORRELATIONS
Tuesday, November 20, 2012
The body is a web of overlapping systems, many of which depend upon one another for effective function. If one system begins to weaken, so do many others. Degenerative aging is a global affair, occurring throughout the body, and so we should not be surprised to find strong correlations between specific forms of age-related decline in many different organs. That doesn't necessarily mean that there is anything profound hiding behind such an association - cells are accumulating damage in all tissues, body-wide systems such as blood vessel elasticity and the immune system are progressively failing, and so decline is everywhere: "Decreased kidney function is associated with decreased cognitive functioning in areas such as global cognitive ability, abstract reasoning and verbal memory. [This] is the first study describing change in multiple domains of cognitive functioning in order to determine which specific abilities are most affected in individuals with impaired renal function. [Researchers] examined longitudinal data, five years apart, from 590 people. They wanted to see how much kidney function had changed over that time period, and whether it was associated with how much cognitive functioning had changed. They were interested in the overall change, but also in specific abilities such as abstract reasoning and verbal memory. "The brain and kidney are both organs that are affected by the cardiovascular systems. They are both affected by things like blood pressure and hypertension, so it is natural to expect that changes in one organ are going to be linked with changes in another.""
AN EXAMPLE OF STEM CELL RESEARCHERS TACKLING AGING
Tuesday, November 20, 2012
Much of the output of the regenerative medicine and tissue engineering fields will be of greatest use to old people: repair and replacement of worn, damaged, and diseased tissue. Unfortunately the cellular environment in an old body works to suppress stem cell activity, and this seems to be a more important factor in the decline of regenerative capacity than age-related damage to stem cells themselves, or the size of the stem cell population. This is perhaps an evolved response to rising levels of cellular damage, and works to suppress cancer risk - but at the cost of an accelerated decline in organ and tissue function. From a practical standpoint, this means that the stem cell research community must learn to control and reverse specific aspects of aging in order for their therapies to have the best possible effect. Otherwise they are throwing good stem cells into an environment that will suppress their activity. This roadblock is actually a good thing: this field of research is very well funded, and thus we all benefit as they find out that aging is in their way. Here is an example of the sort of exploratory early-stage work taking place today: "This study investigated whether cytokine enhancement of a biodegradable patch could restore cardiac function after surgical ventricular restoration (SVR) even when seeded with cells from old donors. ... SVR can partially restore heart size and improve function late after an extensive anterior myocardial infarction. However, 2 limitations include the stiff synthetic patch used and the limited healing of the infarct scar in aged patients. We [placed cytokines onto] porous collagen scaffolds. We seeded human mesenchymal stromal cells from young or old donors into the scaffolds, with or without growth factors. The patches were characterized and used for SVR in a rat model of myocardial infarction. Cardiac function was assessed. In vitro results showed that cells from old donors grew slower in the scaffolds. However, the presence of cytokines modulated the aging-related p16 gene and enhanced cell proliferation, converting the old cell phenotype to a young phenotype. In vivo studies showed that 28 days after SVR, patches seeded with cells from old donors did not induce functional recovery as well as patches seeded with young cells. However, cytokine-enhanced patches seeded with old cells exhibited preserved patch area, prolonged cell survival, and augmented angiogenesis, and rats implanted with these patches had better cardiac function. The patch became an elastic tissue, and the old cells were rejuvenated."
ASTROCYTES AS A POTENTIAL TARGET FOR ALZHEIMER'S THERAPIES
Monday, November 19, 2012
The brain is made up of far more than just neurons; its functions and complex structures require the support of a wide range of specialized cells types. Prominent amongst these supporting cells are the astrocytes. You might recall research from a few months back that indicated a role for age-related changes in astrocytes in the progression of Alzheimer's disease. Following on from that, researchers here report on the use of gene therapy to target astrocytes and potentially reduce the scope of any harmful behavior: "Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes [in] mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes with [a signaling pathway] shown by our laboratory and others to orchestrate biochemical cascades leading to astrocyte activation. After several months of treatment with Gfa2-VIVIT, [the] mice exhibited improved cognitive and synaptic function, reduced glial activation, and lower amyloid levels. The results confirm a deleterious role for activated astrocytes in AD and lay the groundwork for exploration of other novel astrocyte-based therapies."
INTUITION, MORTALITY RATE, AND LIFE EXPECTANCY
Monday, November 19, 2012
Here is a short post with graphs on the relationship between mortality rates and life expectancy: "I read a few weeks ago about a study where vitamin D supplementation reduced all-cause mortality rates by 6%. How many years would that add to life expectancy? I wondered. 6% of a 75-year life span would mean 4½ extra years, I thought, naïvely. I pulled up a mortality table (from the Social Security Admin) and did the calculation in a spreadsheet. The two lines were barely distinguishable. A 6% drop in mortality only increases life expectancy by 7 months. If the death rate did not increase with age, then it would be true that subtracting 6% from mortality would add about 6% to life expectancy. That's where the intuition came from about 4½ years. But with a death rate that increases with age, you "have to work a lot harder" to get an improvement in life expectancy. And in reality, the mortality curve doesn't just rise with age - it rises at an accelerating rate. Once I had set up the spreadsheet, it's easy enough to ask the general question: How much does life expectancy improve for a given change in mortality? The answer I found was: very slowly. ... To add just 5 years to life expectancy, we would need to slash the mortality rate by more than 40%. This is a counter-intuitive statistic - and a discouraging one. There is another perspective: [in] medical research, we are working piecemeal to chip away at the mortality rate from one disease and another. But if the fundamental rate of aging can be slowed, this will push the curve not down but to the right. This will have as much benefit as many decades of progress in cancer and heart disease."