A Recent Interview with Aubrey de Grey of the SENS Research Foundation
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Aubrey de Grey is the co-founder of the SENS Research Foundation, a non-profit organization focused on speeding up development of the biotechnologies needed for human rejuvenation. The underlying model behind the research programs funded is that aging is caused by forms of cell and tissue damage that are currently well defined and understood. Periodic repair of that damage will allow for effective treatment of age-related disease and ultimately indefinite extension of healthy life spans. The only thing separating us from rejuvenation therapies is the matter of building the necessary treatments, a process of a few decades all told were it adequately funded - which is, sadly, still not the case, and one of the reasons why advocacy and grassroots fundraising is so important.

THE INSIGHT: That leads me into the next question: Google has created the California Life Company (Calico), the hedge-fund billionaire Joon Yun has launched the Palo Alto Longevity Prize, so there seems to be a lot of movement in this area. What I'm really fascinated by is - a lot of people are investing a lot of time and money into this area of defeating ageing - if you do implement this 7-stage plan and you see breakthroughs in this area, what's to say that something else, some other large obstacle, doesn't come up? Are you relatively sure that if this 7-stage plan is implemented it will create an open passageway for a longer life?

AUBREY DE GREY: That's a great question. I'm going to give a slightly complicated answer to it - really a two-part answer: the point about the approach that we're taking now is that it's based on this classification of the types of damage that occur in the body and eventually contribute to ill health of old age - classification into seven major categories - and that classification is important because within each category we have a generic approach, a generic therapeutic strategy that should be able to work against every example within that category. So, then your question really divides into two questions. The first question is: are we going to identify new types of damage that fit into the existing classification? The second part of your question is: are we going to find new types of damage that don't fit into the classification - type number 8, and so on?

The answer to the first question is: absolutely, we're going to find more of those; we've been seeing more of those turn-up over the years - throughout the time that I've been working in this area. But, the fact that they fit into the classification means that they're not a problem. It means that, yes, we're going to have to carry on developing additional therapies to address these additional types of damage, but that's kind of okay, because the difficulty of developing those additional therapies will be very slight as a result of the fact that they will be minor variations of the therapies that we already developed to address the examples of that category, that we already knew about.

So, now we move onto the second part of the question, of are we going to identify damage-type number 8, and so on - ones that don't fit into the classification. That's a very important question, but the evidence is looking very good that it's not going to happen. First of all, we can just look and say, "Has it happened anytime recently?" and the answer is absolutely not. SENS has been around for 15 years and, in fact, all of the types of damage that SENS discusses have been well studied and known about for more than 30 years. That's a very long time for nothing to be discovered that breaks the classification.

THE INSIGHT: Have you at any point in your career had an anxious response from governments about your work, like it being a national security threat?

AUBREY DE GREY: No, the government don't behave in that way, because everyone in the government is caught in this trap that I talk about so often, where they're desperate to continue to pretend that any talk of radical life extension is just science-fiction; they don't want to think about it. The reason they don't want to think about it is the reason why the general public don't want to think about it and the reason why quite a lot of scientists don't want to think about it: namely, they don't want to get their hopes up. They really don't want to reengage a psychological battle that they have already lost, that they have already submitted to. They have already made their peace with ageing and the inevitability of declining health, old-age and eventual death; getting into a mode of thinking where maybe science will come along and prevent that from happening or maybe it wont, that's a mindset that disturbs a lot of people; that's a mindset a lot of people would prefer not to even engage in, if the alternative is to continue to believe that the whole thing is science-fiction. It's fatalistic but it's calming.

THE INSIGHT: I'm interested in the psychology of people, I guess you can put them into two camps: one doesn't have an inherent understanding of what you're doing or saying, and the other camp willingly resign themselves to living a relatively short life. You've talked to a whole wealth of people and come across many counter-opinions, have any of them had any merit to you, have any of them made you take a step back and question your approach?

AUBREY DE GREY: Really, no. It's quite depressing. At first, really, I was my own only affective critic for the feasibility - certainly never a case or example of an opinion that amounted to a good argument against the desirability of any of this work; that was always 100% clear to me, that it would be crazy to consider this to be a bad idea. It was just a question of how to go about it. All of the stupid things that people say, like, "Where would we put all the people?" or, "How would we pay the pensions?" or, "Is it only for the rich?" or, "Wont dictators live forever?" and so on, all of these things... it's just painful. Especially since most of these things have been perfectly well answered by other people well before I even came along. So, it's extraordinarily frustrating that people are so wedded to the process of putting this out of their minds, by however embarrassing their means; coming up with the most pathetic arguments, immediately switching their brains off before realising their arguments might indeed be pathetic.

THE INSIGHT: I'd be fascinated to know what your dialogue has been like with pharmaceutical companies and why they have not been more forthcoming?

AUBREY DE GREY: So, there's a somewhat different scenario, because that problem of believing that the whole thing is never going to happen is still true, but there are various other aspects that influence the attitude of... well, beyond big-pharma, the medical industry in general. One thing is, they want to make money; they're worried about quarterly balance sheets, they want to make money now; they don't want to make money 20 years from now. They also don't know that the particular approaches that we're taking are the ones that are going to work; they want to buy up ideas that have already gone through and have been through clinical trials, and then run with them and capitalise on them. They know perfectly well that when things are at the pre-clinical stage - especially when they're only in a conceptual stage and haven't even been tested in mice - that the hit-rate is really low, even when the concept is correct, such that the concept has to be retried multiple times before one comes up with an actual substantiation of the concept that works.

Link: http://www.theinsight.co/aubrey-de-grey-fountain-of-youth

Theorizing on Gene Network Stability and Aging
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Researchers here model the relationship between genetic regulation and aging with an eye towards trying to fit the outcomes in both negligibly senescent and "normally aging" species. It is known that advancing age brings with it epigenetic dysregulation, meaning significant changes in the levels of various proteins produced from their genetic blueprints, and therefore significant changes in cell behavior. Researchers differ on what this means and how close it is to the root causes of aging. In the theories in which aging is an accumulation of damage, then epigenetic changes are far downstream in the chain of cause and consequence; they are a reaction to rising levels of cell and tissue damage.

Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity.

We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals.

Link: http://dx.doi.org/10.1038/srep13589

Towards Cell Therapy as a Replacement for Liver Transplant
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The liver is the most regenerative of mammalian organs, so liver transplantation is the natural first candidate for replacement by some form of cell therapy, delivering cells that will regrow lost and damaged tissue. The details are important in these types of treatment, as seemingly small differences in the methodology of creating and transplanting cells leads to a wide variation in outcomes. A great deal of effort is devoted to finding exactly the right methodology for each tissue type in order to coax cells into carrying out regeneration, and here researchers demonstrate progress for liver tissue in rats:

Liver transplantation is currently the only established treatment for patients with end stage liver failure. However, this treatment is limited by the shortage of donors and the conditional integrity and suitability of the available organs. Transplanting donor hepatocytes (liver cells) into the liver as an alternative to liver transplantation also has drawbacks as the rate of survival of primary hepatocytes is limited and often severe complications can result from the transplantation procedure.

In an effort to find potential therapeutic alternatives to whole liver transplantation and improve the outcomes of hepatocyte transplantation, this study tested the therapeutic efficacy and feasibility of transplanting multi-layered sheets of hepatocytes and fibroblasts (connective tissue cells) into the subcutaneous cavity of laboratory rats modeled with end stage liver failure. The results of the study demonstrated that the cells in the multi-layered hepatocyte sheets survived better than cells transplanted by traditional methods and that the cells proliferated, maintaining liver function in the test animals for at least two months.

The researchers called the fibroblasts "feeder cells" that helped preserve the "high viability and functionality" of the hepatocytes in both in vitro and in vivo studies. The researchers also noted that in other methods of hepatocyte transplantation such as intrasplenic (through the spleen) or intraportal, only a small number of hepatocytes can be transplanted at one time, and many die. By contrast, the transplanted cell sheets showed "dramatically higher albumin expression levels" in vivo one month after transplantation into the subcutaneous cavity.

"Hypoxia is a major cause of poor hepatocyte survival. Therefore, immediately after transplantation, all transplanted cells are supplied with oxygen only from surface diffusion because of the lack of capillary vessels when other methods of transplantation are used." However, in the current study it was observed that merely one week after transplantation, the hepatocyte sheets were permeated with multiple capillary vessels. That the hepatocytes were close to blood vessels confirmed that vascularization is crucial for their survival and function.

Link: http://www.eurekalert.org/pub_releases/2015-08/ctco-ctp082615.php

Fatty Acids Correlate with Longevity in Bird Species
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Birds, like bats, have high metabolic rates due to the demands of flight but are also long-lived in comparison to similarly sized members of other species. This has a lot to do with mitochondria and membrane fatty acid composition, as shown by the evidence in the paper linked below. The membrane pacemaker theory of aging tells us that the genetically determined ratios of specific fatty acids in cell membranes determine resistance to oxidative damage, as well as other important properties in the operation of metabolism that are particularly relevant to mitochondrial function and the ways in which mitochondria become damaged in aging. From a practical point of view, this is one of the things that should steer our attention towards mitochondrial DNA damage as an important contribution to aging, and cause us to prioritize research on methods of repair of that damage.

The evolution of lifespan is a central question in evolutionary biology, begging the question why there is so large variation among taxa. Specifically, a central quest is to unravel proximate causes of ageing. Here we show that the degree of unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species. In these birds, the degree of fatty acid unsaturation is positively related to maximum lifespan across species. This is due to a positive effect of monounsaturated fatty acid content, while polyunsaturated fatty acid content negatively correlates with maximum lifespan. Furthermore, fatty acid chain length unsuspectedly increases with maximum lifespan independently of degree of unsaturation. These findings tune theories on the proximate causes of ageing while providing evidence that the evolution of lifespan in birds occurs in association with fatty acid profiles. This finding suggests that studies of proximate and ultimate questions may facilitate our understanding of these central evolutionary questions.

Link: http://dx.doi.org/10.1111/evo.12754

GDF-11 and Myostatin Correlate with Heart Disease Outcomes
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Here researchers study natural variations in GDF-11 and myostatin levels, finding correlations with health outcomes in heart disease patients. This is one of a number of lines of research emerging from the search for cell signals that differ between old and young tissues, and that might be altered to induce old cell populations to behave more like young cell populations despite the damage they have suffered. In recent years researchers have demonstrated the use of GDF-11 to spur greater levels tissue maintenance in aged mice, for example:

Individuals previously diagnosed with heart disease may be less likely to experience heart failure, heart attacks, or stroke, or to die from these events, if they have higher blood levels of two very closely related proteins. One of these proteins, known as GDF11, has attracted great interest since 2013, when researchers showed that it could rejuvenate old mice. Based on these findings, scientists have speculated that drugs that increase GDF11 levels might reverse physiological manifestations of aging that lead to heart failure in people.

The study population included 1,899 men and women with heart disease who ranged in age from 40 to 85 (average 69 years). Because they already had been diagnosed with stable ischemic heart disease, in which blood supply to the heart is reduced due to coronary artery disease, the participants were at elevated risk for stroke, heart attack, hospitalization for heart failure, and death. Hundreds of the participants experienced one or more of these outcomes during the course of the study, in which they were monitored for nearly nine years.

Researchers used a lab test to measure combined blood levels of GDF11 and a very similar protein called myostatin - the test could not distinguish between the two, because they are quite similar both structurally and functionally. The scientists determined that research subjects who had relatively high blood levels of these two proteins at the beginning of the study - in the top 25 percent of all participants - were less than half as likely to die from any cause, in comparison to participants whose blood levels ranked them in the bottom 25 percent. Those in the highest 25 percent also experienced fewer adverse health events associated with heart disease. "We also found that combined levels of GDF11 and myostatin in humans decline with advancing age, but that the rate of this decline varies among individuals."

In mouse studies published in 2013 researchers found that four weeks of GDF11 treatment in old mice that restored the youthful level of this protein reversed potentially harmful thickening of heart muscle. In humans this thickening of heart muscle, known as ventricular hypertrophy, is associated with aging and contributes to heart failure and death. In the new study, the researchers used standard clinical imaging tests to measure ventricular hypertrophy and found that participants with lower levels of the GDF11 and myostatin proteins were more prone to having thickened heart muscle. "This association with less ventricular hypertrophy and death suggests the possibility that GDF11 might act similarly in humans as in mice. Restoring GDF11 or myostatin to their higher, youthful levels might potentially serve as a so-called 'fountain-of-youth' treatment, but far more work remains to be done,"

Link: https://www.ucsf.edu/news/2015/08/131386/study-fountain-youth-protein-points-possible-human-health-benefit

Proposing a Mechanism to Explain the Association Between Type 2 Diabetes and Alzheimer's Disease
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Type 2 diabetes patients have a considerably greater risk of suffering Alzheimer's disease, as well as many other age-related conditions. It is commonly theorized that this is because the underlying risk factors are the same, which is to say that a sedentary lifestyle and excess fat tissue leading to metabolic syndrome contributes to the development of both conditions. Researchers here propose that type 2 diabetes results in increased generation of the amyloid-β involved in Alzheimer's, because it also has an associated amyloid, and because various different types of amyloid can spur a faster pace of creation of one another once they start accumulating. At this point the evidence is still fairly tenuous, however:

Several proteins have been identified as amyloid forming in humans, and independent of protein origin, the fibrils are morphologically similar. Therefore, there is a potential for structures with amyloid seeding ability to induce both homologous and heterologous fibril growth; thus, molecular interaction can constitute a link between different amyloid forms. Intravenous injection with preformed fibrils from islet amyloid polypeptide (IAPP), proIAPP, or amyloid-beta (Aβ) into human IAPP transgenic mice triggered IAPP amyloid formation in pancreas in 5 of 7 mice in each group, demonstrating that IAPP amyloid could be enhanced through homologous and heterologous seeding with higher efficiency for the former mechanism.

Proximity ligation assay was used for colocalization studies of IAPP and Aβ in islet amyloid in type 2 diabetic patients and Aβ deposits in brains of patients with Alzheimer disease. Aβ reactivity was not detected in islet amyloid although islet β cells express AβPP and convertases necessary for Aβ production. By contrast, IAPP and proIAPP were detected in cerebral and vascular Aβ deposits, and presence of proximity ligation signal at both locations showed that the peptides were less than 40nm apart. It is not clear whether IAPP present in brain originates from pancreas or is locally produced. Heterologous seeding between IAPP and Aβ shown here may represent a molecular link between type 2 diabetes and Alzheimer disease.

Link: http://dx.doi.org/10.1016/j.ajpath.2014.11.016

Studies Show that Elite Athletes Live Longer
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Here I'll point out a review of dozens of studies shows that the balance of evidence points to greater longevity in successful professional athletes. This is one part of a still open question on exercise and long-term health: is it actually better to exercise much more than the recommended moderate levels? There is conflicting evidence from various different types of epidemiological study. The data on professional athletes unfortunately does not show causation, so it may well be that they live longer because more robust individuals tend become professional athletes. In that case had they chosen a different life path, and kept up with regular moderate exercise, they would have had much the same higher than average life expectancy.

Understanding of an athlete's lifespan is limited with a much more sophisticated knowledge of their competitive careers and little knowledge of post-career outcomes. In this review, we consider the relationship between participation at elite levels of sport and mortality risk relative to other athletes and age- and sex-matched controls from the general population. Our objective was to identify, collate, and disseminate a comprehensive list of risk factors associated with longevity and trends and causes of mortality among elite athletes.

Fifty-four peer-reviewed publications and three articles from online sources met the criteria for inclusion. An overwhelming majority of studies included in this review reported favorable lifespan longevities for athletes compared to their age- and sex-matched controls from the general population. In fact, only two studies reported lower lifespan longevities in athletes relative to the controls. Although our overall understanding of modifiable and non-modifiable factors that contribute to mortality risk in elite athletes remains limited, in part due to methodological and data source inconsistencies, some trends emerged from our investigation. In particular, our review supports previous conclusions that aerobic and mixed-sport athletes have superior longevity outcomes relative to more anaerobic sport athletes. In addition, playing position and weight, as well as education and race, appeared to be consistent indicators of mortality risk, whereas other mechanisms such as handedness, precocity, and names and initials appeared to be less consistent and/or examined.

As a variety of confounders may impact longevity, the reasons for the differences in lifespans between elite athletes and the general population are likely to be multifactorial. There are several possible explanations of increased survival in the elite athlete cohort; namely, participation in higher volumes of exercise training leading to higher physical fitness levels, the likelihood that elite athletes are comprised of the healthiest and fittest individuals, and the maintenance of active and healthy lifestyles later in life. The extents to which these confounders contribute to mortality risk are still largely unknown however, as survival statistics may undermine the interplay of complex socioeconomic factors. For example, medical care accessibility made available by higher income may improve the life expectancy of athletes when compared to other groups. Further, plenty of corroborating evidence suggests health-care services alone do not result in improved health outcomes, but a variety of social factors such as education and employment produce these widespread biases in health. As a result, the historical investigations of elite athletes and longevity outcomes need to be cautiously interpreted and discussed in the contexts of a variety of possible influential factors of mortality.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534511/

A Look at Blastema Mechanisms in Zebrafish Regeneration
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In species capable of regrowing limbs and organs, such as salamanders and zebrafish, tissues form a blastema at the site of regeneration. This mass of cells recapitulates much of the behavior of embryonic development, including the complex signal interactions that steer the construction of replacement tissue. How exactly are the correct structures produced? Researchers hope that understanding the underlying processes will enable the inducement of similar cellular activity to heal injuries and age-damaged tissues in our species. That better understanding may also have other applications, such as in ongoing efforts to find a robust way to build complex blood vessel networks to support engineered tissue, which at the moment is one of the limiting factors preventing the creation of entire organs from a patient's own cells:

When parts of the zebrafish tailfin are injured by predators, or are experimentally amputated, the lost tissue is replaced within three weeks. Zebrafish fins consist of a skin that is stabilized by a skeleton of bony fin rays; similar to an umbrella that is supported by metallic stretchers. Fin rays are formed by bone-producing cells, the osteoblasts. In order to rebuild an amputated fin, a large number of new osteoblasts have to be formed by cell divisions from existing osteoblasts.

Retinoic acid is required to regulate the addition of bone material in growing fish. During regeneration, mature osteoblasts have to revert to an immature osteoblast precursor, which enables the switch from bone synthesis to cell division. The switch requires retinoic acid levels to drop below a critical concentration. However, upon amputation the tissue beneath the wound initiates a massive bout of retinoic acid synthesis that is required to mobilize cell division in the fin stump. How do mature osteoblasts circumvent this dilemma? The answer: osteoblasts that participate in regeneration transiently produce Cyp26b1, an enzyme that destroys and inactivates retinoic acid. Protected by this process, osteoblasts are able to rewind their developmental clocks, thus turning into precursor cells that contribute to a pool of undifferentiated cells, the blastema. Cells in the blastema pass through a number of cell divisions to provide the building blocks for the regenerated fin.

However, these cell divisions are supported by high concentrations of retinoic acid, which poses the next predicament: The reversion to become a mature osteoblast is inhibited by high levels of retinoic acid. Connective tissue in those areas of the blastema from which new mature osteoblasts eventually emerge produces the retinoic acid killer Cyp26b1. This lowers the local concentration of retinoic acid, so that osteoblast precursors are again able to mature and produce new fin rays. Other parts of the blastema, which replenish the supply of cells needed for regeneration to occur, continue to produce retinoic acid. "This is an elegant mechanism that ensures a gradient of cells experiencing high and low levels of retinoic acid. This allows two processes to run in parallel during regeneration: Proliferation for the production of all cells that replace the lost structure and redifferentiation of osteoblasts where the skeleton re-emerges."

How is the exact shape of the fin skeleton regenerated? In order to form new fin rays, newly formed osteoblasts have to align at the correct positions. Osteoblasts are ultimately guided to target regions by a signaling protein called Sonic Hedgehog. This is produced locally in the epidermis, a skin-like layer that covers the fin and the blastema. However, signal production only occurs in locally restricted cells that are free of retinoic acid. Such epidermal cells produce Cyp26a1, an enzyme that is functionally similar to Cyp26b1. Lastly, it emerged that osteoblasts themselves exert a piloting function for other cell types, particularly mesenchymal cells and blood vessels that also have to be directed to appropriate destinations during the rebuilding process. "The re-emergence of the skeletal pattern relies on a navigation system with interacting parts. Initially, retinoic acid is inactivated where new rays are to form. This allows the local production of a signal that pilots immature osteoblasts to areas where existing fin rays are to be extended. Interestingly, over the course of regeneration other cell types in the blastema are informed by osteoblast precursors to respect the boundaries between emerging fin rays."

Link: http://www.eurekalert.org/pub_releases/2015-08/ub-hzr082415.php

Radiation Hormesis Studied in Flies
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Hormesis is the process whereby a little damage leads to a lasting increase in the activities of cellular repair mechanisms, with the outcome of a net gain in systems integrity and function. Hormesis is involved in a majority of the interventions shown to modestly slow aging in at least some short-lived species, such as low level radiation treatment. Here researchers add to the data on radiation hormesis and life span in flies, showing life extension of 3% to 7% that varied by gender but, perhaps surprisingly, not by dose:

Although there are many common mechanisms of response of organism and cell to irradiation and other stresses (thermal, oxidative, etc.), their principal difference is a significant role of DNA damage on the biological effects of ionizing radiation. However, these differences are attributed mostly to high dose rates. In the case of low dose radiation, direct effects of irradiation such as clustered DNA damage and DNA double strand breaks are minimal, whereas indirect DNA damages caused by the induction of reactive oxygen species become the primary result. In high doses, adverse effects accumulate in the tissues in a deterministic manner that depends linearly on the dose, but in low doses the effects are stochastic, non-linear on the dose, and depend mainly on the efficiency of the stress response's protective mechanisms.

Therefore, low doses of radiation can be regarded as moderate stress, which is known to induce hormesis. Indeed, in our previous work, and in the work of other authors it has been revealed, that relatively low dose exposure (20-75 cGy) of fruit flies on immature preimaginal stages in some cases has long-term effects that lead to an increased life span and resistance to other stresses, such as hyperthermia. It is known that preimaginal stages of Drosophila have comparable radiosensitivity to mammals. At the same time, adult individuals, due to the postmitotic state of most tissues, are about 100 times more radioresistant. Other researchers have revealed that irradiation of Drosophila individuals in the imago stage in doses from 0.1 to 400 Gy causes a statistically significant effect on lifespan and gene expression only if the dose is higher than 100 Gy. At the same time, in our recent work on comparing the effects of irradiation in the adult Drosophila male and female at the 20 cGy dose rate, we observed some differentially expressed genes.

Although some changes in life extensity in males were identified (the effect of hormesis after the exposure to 5, 10 and 40 cGy) as well as in females (the effect of hormesis after the exposure to 5 and 40 cGy), they were not caused by the organism "physiological" changes. This means that the observed changes in life expectancy are not related to the changes of organism physiological functions after the exposure to low doses of ionizing radiation. The identified changes in gene expression are not dose-dependent, there is not any proportionality between dose and its impact on expression. These results reflect nonlinear effects of low dose radiation and sex-specific radio-resistance of the postmitotic cell state of Drosophila melanogaster imago.

Link: http://dx.doi.org/10.1371/journal.pone.0133840

Generating Oligodendrocytes to Spur Remyelination
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Researchers here investigate a way to generate more oligodendrocytes in the brain, the cells responsible for creating the myelin sheathing essential to correct function of the nervous system. The presence of more of these cells improves the pace of myelin generation, which may form the basis for therapies to treat the medical conditions that involve accelerated loss of myelin. It is also the case that some loss of myelin maintenance will occur for all of us in old age due to growing cellular dysfunction and damage. This likely contributes to cognitive decline and other manifestations of old age, so it is worth keeping any eye on the development of potential treatments in this area.

Scientists found that deleting from the adult brain a protein necessary for early development actually fosters the growth of cells that generate myelin, the important protective coating neurons need to function. The research on lab animals provides new insight into how critical brain cells are generated. The finding may lead to improved treatments for brain injury, demyelinating diseases, certain developmental diseases and brain tumors. Researchers studied Nuclear Factor I X (NFIX), a transcription factor - a protein that turns genes on and off. NFIX is required for normal development of the early brain and it's known that losing NFIX before birth results in a number of rare human diseases, characterized by severe developmental and physiological defects. However, the new study shows that the loss of NFIX is necessary at a certain point in order for some brain cells to develop normally.

Oligodendrocytes surround neurons, which transmit electrical signals in the brain, protecting them from damage and speeding the transmission of those signals. The research shows that as neural stem cells differentiate into oligodendrocytes, the expression of NFIX decreases, apparently an essential step in the normal formation of the myelin-making cells. "In terms of a treatment, this could lead to the development of a small molecule that could be used to shut off NFIX activity in MS patients, thus promoting the growth of more oligodendrocytes." This study and previous ones have found that loss of NFIX could also increase the growth of adult neural stem cells, which, in turn, generate new neurons in adult animals. "This could also help us find ways to stimulate new neuron production in diseases where neurons die, such as in Alzheimer's and Parkinson's diseases and in spinal cord injury." The researchers' next step is to learn which genes are regulated by NFIX, and the best way to promote this increase in both oligodendrocytes and neural stem cells.

Link: http://www.buffalo.edu/news/releases/2015/08/018.html