The logic of evolution by natural selection is straightforward. Within any population, the alleles of individuals that produce the most breeding descendants will increase in frequency in successive generations at the expense of the alleles of individuals less successful at reproduction. To be successful at leaving descendants requires that organisms also be successful at surviving - so that they live long enough to reach reproductive age and afterward continue reproducing. By this logic and process, natural selection ultimately produces individuals superbly designed to survive and reproduce in their environment.

From this perspective, aging presents an evolutionary puzzle. If continued survival and reproduction should always be favored by natural selection, why is aging - which in evolutionary terms can be defined as the age-related decline in survival rate and reproduction - nearly ubiquitous in the natural world? Or as George Williams put it, "it is remarkable that after a seemingly miraculous feat of morphogenesis, a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed." Why doesn't evolution, in other words, mold the biology of organisms such that aging never occurs?

One possible solution to this conundrum is that evolution does in fact mold the biology of organisms such that they never age in their natural environment, that is, the environment in which they evolved. Aging might seldom occur in nature and only become evident when animals live much longer than they ever would in the wild, such as when we protect them from natural hazards by making them pets or livestock, keeping them in zoos or, as in the case of ourselves, organizing them into climate controlled, predator-free civilizations. Some biomedical gerontologists believe this hypothesis to be the case. But it is not and, in fact, dozens of field studies to date have identified that aging in wild animals is rampant if not close to ubiquitous.

Thus, there is a real puzzle to be solved as to how aging develops in natural populations. Fortunately, evolutionary biologists have cracked this mystery. An evolutionary mechanism of aging was hypothesized 60 years ago to be the genetic trade-off between early life fitness and late life mortality. Genetic evidence supporting this hypothesis was unavailable then, but has accumulated recently. These tradeoffs, known as antagonistic pleiotropy, are common, perhaps ubiquitous. George Williams' 1957 paper developed the antagonistic pleiotropy hypothesis of aging, which had previously been hinted at by Peter Medawar. Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge.

No genes of the sort hypothesized by Williams were known 60 years ago, but modern molecular biology has now discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life and enhance health under laboratory conditions. Does this provide strong support for Williams' hypothesis? What are the implications of Williams' hypothesis for the modern goal of medically intervening to enhance and prolong human health? Overall, whenever antagonistic pleiotropy effects have been seriously investigated, they have been found. However, not all trade-offs are directly between reproduction and longevity as is often assumed. The discovery that antagonistic pleiotropy is common if not ubiquitous implies that a number of molecular mechanisms of aging may be widely shared among organisms and that these mechanisms of aging can be potentially alleviated by targeted interventions.

SENS Research Foundation would like to send a huge thank you to Vitalik Buterin for donating 350,000 worth of ethereum to our end of year campaign!

The office of Aubrey de Grey, chief science officer of SENS (short for the very catchy Strategies for Engineered Negligible Senescence), is my first stop in my journey into the strange and surprisingly overlapping worlds of cryptocurrency and life-extension. But de Grey is not like most tech entrepreneurs, nor is he like most longevity researchers. He doesn't buy into the health fads popular amongst his peers, like calorie restriction. He's not hoarding the blood of spritely teenagers (though tech billionaire Peter Thiel, who may or may not be interested in youthful blood infusions, is a SENS donor). And, while he says that cryonics - in which bodies are preserved at low temperatures - is "an extremely valuable and neglected area of medicine," the whole freezing-and-thawing process is not where his still-beating heart lies.

De Grey's plan is more ambitious than resurrection: He wants to reverse aging all together. As he outlines in his 2007 book Ending Aging, his strategy is to discover therapies that address the "diseases and disabilities of aging." Whereas most biogerontologists focus on the complex metabolic processes that cause aging damage, de Grey argues that the focus should be on the forms of damage themselves - like nuclear mutations, or the intracellular "junk" that forms as we get older. In short: Focus on treating the underlying causes, not the symptoms of aging.

Though he has plenty of critics, de Grey's bold approach has also garnered him scores of devoted fans. As he sits stroking his Rip Van Winkle-worthy beard, it's easy to see how de Grey's achieved this "kind of a spiritual leader status," as he calls it. He dives easily into intricate explanations of two research projects unfolding in the lab down the hall, eagerly describing how one studies mitochondrial mutations, which are thought to cause an increase in oxidative stress. The other looks at atherosclerosis, the narrowing and hardening of artery walls. If we understood more about this buildup, the logic goes, we could better clean it up before too much damage is done.

Though he attends lab meetings and oversees the SENS Research Foundation's research, his primary task is convincing the general public that death is, in fact, bad and that we should be doing everything we can to stop it. This focus on messaging suits him just fine. Back in April, at a San Francisco blockchain conference called Block 2 the Future, de Grey began his talk with a disclaimer: "I probably ought to start by emphasizing that I don't know fuck-all about cryptocurrencies. I am really only here because I have apparently quite a significant fan base in this community, and I am delighted that I do." He was referring to the intertwining relationship between blockchain enthusiasts and life-extension advocates, which can feel less like a Venn diagram and more like overlapping circles. There's a history of members of the blockchain community donating to life-extension efforts. Billionaire and cryptocurrency investor Michael Novogratz donated to the organization that predated SENS in the early 2000s, and the number of cryptocurrency donors has increased exponentially since. In the past year or so, SENS has received more than 6.5 million in cryptocurrency donations, including 2.4 million from Ethereum cofounder Vitalik Buterin last December.

Pine, the anonymous individual behind the Pineapple Fund who donated 55 million worth of bitcoin to various charities last year, gave 2 million of that to SENS. A few other anonymous crypto donors gave around 1 million each, says de Grey. And other cryptocurrency heavy-hitters have long-term involvements with SENS, too. De Grey believes that crypto's philanthropic donors skew younger, like with Buterin, just 24, who became a fan after reading Ending Aging as a teenager. De Grey likes to call this new generation of donors "Children of the Revolution" - and he's called out older people for not doing their part. "It's a huge embarrassment to the kind of wealthy individuals of my age, like Peter Thiel or Jeff Bezos or the Google Twins or whatever, who are ostensibly really supportive of all of this, but who have put very small, if any, proportions of their net worth into supporting it. Peter is a shining example of someone who has put some money in - but let's face it, he could have put more in."

For now, the business of life extension is still a business - even nonprofits like the SENS Research Foundation need to fund their research. Despite the techno-spiritual affinity, the main reason life-extension proponents are regulars on the blockchain circuit is economic: They're chasing crypto's money.

Much of the work in our laboratory during the last 30 years was directed at identifying mechanisms of extended longevity of mice with growth hormone (GH)-related mutations and answering the question how major reduction or absence of normal endocrine signals can have major beneficial impact on healthspan and lifespan. Both GH-deficient and GH-resistant mice have many phenotypic characteristics that presumably account for, or contribute to, healthy aging and extended longevity and, thus, represent likely mechanisms of these effects.

These characteristics include increased resistance to multiple stressors such as free radicals and toxins, reduced chronic low grade inflammation, senescent cell burden, and expression of pro-inflammatory cytokines in the central nervous system, reduced mTORC1 and increased mTORC2 signaling, as well multiple adaptations of carbohydrate, lipid, and energy metabolism. Many of the physiological characteristics of GH-related mutants interact, forming a complex network of mechanisms.

For example, reductions in the levels of pro-inflammatory cytokines, the number of senescent cells, the secretory capacity of pancreatic beta cells, and mTORC1 signaling, interact with increased levels of adiponectin and reduced GH signaling to improve insulin sensitivity, while each of these factors also influences aging by other mechanisms. We believe that the remarkable extension of longevity in mice with genetic GH deficiency or resistance results from alterations in multiple mechanisms of aging and interactions among these alterations.

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms.

GH signal-deficient mice, including Snell, Ames, Little, GHR-/- , and Fgf21 Tg dwarf mice, showed increased lifespans and smaller body masses than wild type (WT) mice. Therefore, body size was strongly dependent on GH action. This consistent trend suggests an inverse correlation between size and lifespan. However, small size can not be used as a general indicator of longevity, because Kl Tg, Irs2 +/-, p66 Shc-/-, and mtor +/-; mlst8 +/- mice had normal body masses like WT mice, but showed longer lifespans than WT. In addition, GHA Tg mice had normal lifespans like WT mice, and Kl -/- and Irs2 -/- mice showing dramatically shorter lifespans also had a dwarfism phenotype. Therefore more work is needed to elucidate factors contributing to the lifespan of these mice.

Researchers have proposed that the irisin hormone serves as a link between exercise and its beneficial effects on health, including burning fat, strengthening bones, and protecting against neurodegenerative diseases. Until now, however, researchers hadn't identified a specific molecular receptor for irisin - in effect, a docking structure allowing irisin to bind to cells and tissues. They are now reporting that the irisin receptor is a group of proteins called integrins situated on the surface of osteocytes.

Osteocytes are cells that act as the "command and control unit" for bone remodeling - that is, the loss and replenishment of bone that occurs both normally and in pathological states. Some research previously found that intermittent injections of irisin increased bone density and strength in mice. Now that it has shown that irisin targets the osteocyte through a specific receptor, the irisin-bone connection can be explored more mechanistically.

Osteocytes gradually die off with age, and their loss is believed to be a cause of age-related osteoporosis, the thinning and weakening of bones. In cell culture, the scientists observed that treating osteocytes with irisin protected them from being killed by hydrogen peroxide - a simulation of age-related death. The experiments also showed that treating osteocytes with irisin increased their production of sclerostin, a protein that triggers bone remodeling, and injecting irisin into mice raised their sclerostin levels. Sclerostin actually triggers the breakdown of bone, which might seem harmful rather than helpful. However, the intermittent breakdown of bone seems to be interpreted as a signal to remodel and build bones. So how could manipulating irisin be used therapeutically? Some form of intermittent irisin treatment might work.

It was published recently that a therapy to reverse aging will be a reality within five years. What will be its mechanism of action, roughly?

There will not be just one medicine; there will be a lot of different medicines, and they will all have different mechanisms of action. For example, some of them will be stem cells, where we put cells back into the body in order to replace cells that the body is not replacing on its own. Sometimes, they will be drugs that kill cells that we don't want. Sometimes, they will be gene therapy treatments that give cells new capabilities to break down waste products, for example. Sometimes, they will be vaccines or other immune therapies to stimulate the immune system to eliminate certain substances. Many different things. In five years from now, we will probably have most of that working. I do not think that we will really have it perfect by then; probably, we will still be at the early stages of clinical trials in some of these things. Then, we will need to combine them, one by one, to make sure that they do not affect each other negatively. So, there will still be some way to go. But, yes, I think it's quite likely that in five years from now, we will have everything, or almost everything, in clinical trials.

Then clinical trials for seven years until it's perfected. Don't clinical trials usually take a long time?

It depends. For example, in aging, because there is this progressive accumulation of damage, you could have therapies that slow down the rate at which damage accumulates, or you could have therapies that repair the damage that has already happened. The second type of therapy is what we think is going to be most effective and is going to be easiest to do, and you can see results from that very quickly, like in one or two years. Now, of course, you still want to know what happens later on, but the first thing is to determine whether this is working at all, and as soon as it starts to work, then you can start to make it available. Clinical trials are changing in that way. Historically, clinical trials had to be completed before anybody could get these drugs, but now we are getting new policies; there is a thing called adaptive licensing, which is becoming popular in the US and elsewhere, where the therapy becomes approved at an earlier stage, and then it's monitored after that.

Beyond the humanitarian perspective of avoiding the pain and suffering that comes with old age, if increasing the years of healthy life in people will significantly reduce health care spending by governments, why don't they promote research in this area?

You're absolutely right. It's quite strange that governments are so short-sighted. But, of course, the real problem is psychological: it's not just governments that are short-sighted. Almost everybody in the world is short-sighted about this. The reason I believe why that's true is people still can't quite convince themselves that it's going to happen. Since the beginning of civilization, we have known that there is this terrible thing called aging, and we have been desperate to do something about it, to get rid of it. And people have been coming along, ever since the beginning of civilization, saying, "Yes, here's the solution, here's the fountain of youth!" And they've always been wrong. So, when the next person comes along and says they think they know how to do it, of course, there is going to be some skepticism until they have really shown that it's true. Of course, if you don't think it's going to work, then you're not going to support the effort financially. It's very short-sighted, but it's understandable.

Why do you think that the pharmaceutical industry does not devote its research and development efforts to this area, which causes the death of 100,000 people every day?

Today, the pharmaceutical industry is geared toward keeping old people alive when they are sick. It makes its money that way. It's not just the pharmaceutical industry, it's the whole of the medical industry. And so, most people say that they are worried that maybe the pharmaceutical industry will be against these therapies when they do come along. I don't think that's true at all. I think they will be in favor because people will be in favor, but people are not really in favor yet. People don't really trust preventive medicine. They think "Okay if I am not yet sick…" They don't trust medicine in general; they know that this is experimental. So, when they are not yet sick, they think "Well, I'll wait until I am sick," but we can change that. Eventually, people will understand that it's going to be much more effective to treat yourself before you get sick, and then the whole medical industry will just respond to that; they will make the medicines that people want to pay for.

Stroke is a leading cause of death and chronic disability in adults, causing a heavy social and economic burden worldwide. However, no treatments exist to restore the neuronal circuitry after a stroke. The mammalian brain has only a limited ability to regenerate neuronal circuits for functional recovery. While most neurons are generated during embryonic brain development, new neurons continue to be produced in the ventricular-subventricular zone (V-SVZ) of the adult brain.

In a rodent ischemic stroke model induced by transiently blocking the middle cerebral artery, the most commonly affected vessel in human patients, some V-SVZ-derived neuroblasts migrate toward the lesion, where they mature and become integrated into the neuronal circuitry. However, the number of these new neurons is insufficient to restore neuronal function. Within a few days after stroke, astrocytes, a major population of macroglia, in and around the injured area become activated, exhibiting larger cell bodies, thicker processes, and proliferative behavior. The migrating neuroblasts must navigate through this astrocyte meshwork to reach the lesion.

The research team demonstrated that neuroblast migration is restricted by the activated astrocytes in and around the lesion. In normal, olfaction-related migration, neuroblasts secrete a protein called Slit, which binds to a receptor called Robo expressed on astrocytes. Slit alters the morphology of activated astrocytes at the site of neuroblast contact, to move the astrocyte surface away and clear the neuroblast's migratory path. However, in the case of brain injury, the migrating neuroblasts actually down-regulated their Slit production, crippling their ability to reach the lesion for functional regeneration. Notably, overproducing Slit in the neuroblasts enabled them to migrate closer to the lesion, where they matured and regenerated neuronal circuits, leading to functional recovery in the post-stroke mice.

Although variations in the rate of aging across species suggests a strong role of genetics, the heritability of lifespan observed within each species is less than 35%, indicating that the environment plays an predominant role in aging. The reliability theory of aging portrays organisms as mechanical systems that contain components with varying probabilities of failure. Complex organisms have redundancy in vital systems (perhaps better understood as the capacity to self-repair) so that every occurrence of damage does not result in death, but rather, the organism accumulates defects (due to inefficient repair) that ultimately exhaust reparative capacity.

While, in the context of this theory, the frequency and severity of damage has been thought to be determined, at least in part, by the environment, there are few, if any, conceptual models with robust explanatory power and predictive capacity to account for the influence of the environment on the rate of aging. In this regard, the concept of the envirome, analogous to the genome, could provide a useful ontological model for studying the relationship between the environmental circumstance and genetic predisposition.

Broadly, the envirome could be thought of as an integrated set of natural, social, and personal environmental domains. The natural domain of the environment consists of ecological and geographic conditions, whereas the social environment, which lies within the natural environment, includes the built environment, social networks, and culture. Lastly, the personal environment lies within the social environment and includes the factors specific to an individual. In this model, interactions of the natural and social domains of the envirome with the genome could be viewed as the major determinants of aging. Aging, in turn, could be viewed as a progressive accrual of damage or unrepairable injury that results from a mismatch between the envirome and the genome and from exposure to adverse environmental conditions such as low socioeconomic status, smoking, or air pollution.

ApoE is a lipid and cholesterol carrying protein that is primarily produced by the liver and is responsible for plasma lipid homeostasis. It occurs in three major isoforms in humans known as ApoE2, ApoE3 and ApoE4, with ApoE3 being the most frequent allele (~77% homozygosity) followed by ApoE4 (~15-20% allele frequency) which is present in more than 50% of late onset Alzheimer's disease patients. The effect of ApoE4 on amyloid-β (Aβ) accumulation through impaired Aβ turnover, increased aggregation, and thus plaque formation is allele dosage-dependent and this can partly explain its effect on the earlier age of disease onset. However, ApoE4 can independently impair synapse function and Ca2+ homeostasis by disrupting the endocytic transport and recycling of synaptic ApoE receptors and the excitatory AMPA and NMDA type glutamate receptors that are regulated by those ApoE receptors and that are consequently trapped with them in the same vesicles.

The molecular basis by which ApoE4 causes the disruption of normal endosomal vesicle transport and recycling is most likely the result of its propensity to unfold and assume a 'molten-globule' conformation upon entering an acidic environment. ApoE4 differs from ApoE3 by a single amino acid, which alters its isoelectric point to coincide with the pH of ~6.5 that is present in the early endosome. We hypothesized that this isoelectric charge neutralization would make ApoE4 prone to aggregation, which could be the molecular basis for the ApoE4-induced and gene dosage-dependent recycling defect.

pH in the early endosome is maintained by the opposing functions of the proton pump, which decreases vesicular pH, and the Na+/H+ exchanger NHE6, which increases it. Here, we have investigated the role of NHE6 inhibition as a means of lowering endosomal pH, away from the isoelectric point of ApoE4. We found that this simple pharmacological intervention releases the endosomal ApoE4 block, restores the normal trafficking of ApoE receptors and glutamate receptors in neurons and corrects the functional defects in vitro and in vivo. Together these findings suggest that drugs that make vesicles in neurons more acidic may have the potential to help prevent individuals that carry the ApoE4 protein from developing Alzheimer's disease. Current drugs that target NHE6 also affect other molecules, which can often lead to side effects. A next step will be to develop tailor-made, small molecule drugs that can enter the brain efficiently and selectively block NHE6.

The present study was undertaken to provide a better insight into the relationship between different levels of body mass index (BMI) and changing risk for hypertension, using an unselected sample of participants assessed during the Longevity Check-up 7+ (Lookup 7+) project. Lookup 7+ is an ongoing cross-sectional survey started in June 2015 and conducted in unconventional settings (i.e., exhibitions, malls, and health promotion campaigns) across Italy. Candidate participants are eligible for enrollment if they are at least 18 years of age and provide written informed consent. Specific health metrics are assessed through a brief questionnaire and direct measurement of standing height, body weight, blood glucose, total blood cholesterol, and blood pressure.

The present analyses were conducted in 7907 community-living adults. According to the BMI cutoffs recommended by the World Health Organization, overweight status was observed among 2896 (38%) participants; the obesity status was identified in 1135 participants (15%), with 893 (11.8%) participants in class I, 186 (2.5%) in class II, and 56 (0.7%) in class III. Among enrollees with a normal BMI, the prevalence of hypertension was 45% compared with 67% among overweight participants, 79% in obesity class I and II, and up to 87% among participants with obesity class III. After adjusting for age, significantly different distributions of systolic and diastolic blood pressure across BMI levels were consistent. Overall, the average systolic blood pressure and diastolic blood pressure increased significantly and linearly across BMI levels. In conclusion, we found a gradient of increasing blood pressure with higher levels of BMI. The fact that this gradient is present even in the fully adjusted analyses suggests that BMI may cause a direct effect on blood pressure, independent of other clinical risk factors.

Researchers have found that activation of a specific transcription factor induces in adult stem cells a phenomenon called pathological quiescence. This is when adult stem cells are rendered incapable of responding to injury by producing myelin-forming oligodendrocytes. The failure to remyelinate is the key feature of multiple sclerosis (MS). The work defines the role of the previously undescribed transcription factor known as PRRX1 in human oligodendrocyte progenitor cells, the cells that generate myelin-forming oligodendrocytes.

Current MS research focuses largely on drugs that induce the differentiation of human oligodendrocyte progenitors. In contrast, the UB research presents a novel concept for the development of new drugs based on blocking the pathological quiescence of progenitors. The research demonstrated that PRRX1 expression results in the cell cycle arrest and quiescence of oligodendrocyte progenitors, which disabled the production of myelin. In an animal model of leukodystrophy, the group of genetic disorders in which myelin fails to form or is destroyed, pathological quiescence induced by PRRX1 prevented cell colonization of white matter and effective myelin regeneration by transplanted human oligodendrocyte progenitors.

The researchers also found that blocking expression of this transcription factor prevented the negative effects of proinflammatory cytokines, such as interferon-γ, which regulates its expression. "Blockade of PRRX1 expression prevents the negative effects of interferon-γ, suggesting that PRRX1 expression might be a viable target in inflammatory diseases, such as multiple sclerosis, where interferon-γ may prevent successful myelin regeneration."

Cardiac hypertrophy is a prominent pathological feature of age-related heart failure. Using the parabiosis model, it has been demonstrated that age-related cardiac hypertrophy can be reversed via exposure to a young circulatory environment. These experiments revealed that age-related cardiac hypertrophy is at least in part mediated by circulating factors, such as GDF11, which is able to reverse the condition.

The reversal of cardiac hypertrophy in old mice exposed to a young circulation cannot be explained by a reduction in blood pressure in the older mice. An extensive proteomics analysis was performed on the serum and plasma of the animals. GDF11 was reduced in the circulation of aged mice and its levels were restored to those in young animals by parabiosis. A significant decrease was also found in both GDF11 gene expression and GDF11 protein levels in the spleens of old mice. These results suggest exciting therapeutic approaches for the management of age-related cardiac hypertrophy by restoring youthful levels of circulating GDF11.

Recently, the goal of a study in old mice was to reexamine the possibility to restore youthful levels of GDF11 by injecting recombinant GDF11 (rGDF11) and thus reversing cardiac hypertrophy and imparting a young phenotype to the old heart. The conclusions were that recombinant GDF11 (rGDF11) had no effect on cardiac structure and cardiac pump function; these results do not support the concept that GDF11 could be an anti-aging compound.

Muscle satellite cells are responsible for the postnatal growth and major regeneration capacity of adult skeletal muscle. Previous studies demonstrated that impaired regeneration in aged muscle can be reversed by parabiosis, which exposes aged tissues to a youthful systemic environment and restores injury-induced satellite cell activation by the up-regulation of Notch signaling. To determine whether supplementation of GDF11 from the young partner might underlie changes in skeletal muscle in the condition of heterochronic parabiosis, aged mice were treated with daily intraperitoneal injections of rGDF11 to increase systemic GDF11 levels.

After 4 weeks, satellite cell frequency, determined by flow cytometry, and function increased in the muscles of rGDF11-treated mice, whereas other myofiber-associated mononuclear cell populations were unaffected. Aged mice treated with rGDF11 also showed increased numbers of satellite cells with intact DNA. These results indicate that GDF11 is able to regulate muscle aging and may be therapeutically suitable for skeletal muscle dysfunction.

The study involved 160 people with an average age of 65 and risk factors for heart disease, such as hypertension, who did not have dementia but reported problems with thinking skills. All participants were identified as having cognitive impairments without dementia and were sedentary at the start of the study. Researchers examined the effects of both exercise and diet, specifically the Dietary Approaches to Stop Hypertension (DASH) diet, which is a low sodium, high fiber diet rich in fruits and vegetables, beans, nuts, low fat dairy products, whole grains, and lean meats. The DASH diet was designed specifically for individuals with high blood pressure.

Participants were randomly assigned to one of four groups: aerobic exercise alone; DASH diet alone; both aerobic exercise and the DASH diet; or health education, which consisted of educational phone calls once every one or two weeks. People assigned to the exercise groups exercised three times a week for 45 minutes each session which included 10 minutes of warm-up exercises and 35 minutes of aerobic exercise, such as walking, jogging, or cycling on a stationary bicycle. At both the beginning and end of the six-month study, researchers evaluated participants' thinking and memory abilities with standardized cognitive testing, cardiorespiratory fitness with treadmill stress testing, and heart disease risk factors with screenings for blood pressure, blood glucose and lipids. They also used questionnaires and food diaries to measure how closely the participants followed the DASH diet.

Researchers found that participants who exercised showed significant improvements in thinking skills when compared to those who did not exercise. Those who took part in both the exercise and diet had average scores of nearly 47 points on the overall tests of executive thinking skills, compared to an average score of about 42 points for those with exercise and diet alone and about 38 points for those who just received health education. There was no improvement in participants who only consumed the DASH diet, although those who exercised and consumed the DASH diet had greater improvements compared to health education controls.

At the start of the study, the participants had average scores for select subtests of executive function for people who were age 93, which was 28 years older than their actual chronological age. After six months, participants who exercised and followed the DASH diet saw their average executive function scores correspond with people who were age 84, a nine-year improvement. For those who received only health education, their performance on executive function tests worsened by a half year from their scores at the start of the study.

EnClear Therapies was conceived with the purpose of developing novel device-based therapies to treat patients with neurodegenerative disease. Toxic proteins are generated in ALS and FTD patients with C9orf72 mutations. These proteins travel through the brain and spinal fluids and are taken up by neurons of the motor system that are very sensitive to their toxicity which leads to degeneration of these neurons leading to paralysis.

EnClear has developed a technology which clears these toxic proteins from the brain and spinal fluids of C9orf72 ALS and FTD patients. We are now developing this technology into a device that will recirculate the brain and spinal fluids while the toxic proteins are rendered harmless. With this technology Enclear aims to stop or significantly slow down the neuronal degeneration in ALS and FTD patients with C9orf72 mutations. This technology can potentially be used for other forms of ALS and FTD in which toxic prion like proteins propagate through the brain and spinal fluids.

Similar to ALS, Progressive Supranuclear Palsy (PSP) is hallmarked by the buildup of toxic proteins (in this case tau) in the brain. As with ALS, the toxic proteins travel through the brain and spinal fluids and are taken up by neurons that are very sensitive to their toxicity which leads to degeneration of these neurons leading to paralysis. EnClear Therapies aims to halt the progression of PSP by rendering the tau harmless through the same mechanism used for ALS.