Fight Aging! Newsletter, April 15th 2013

April 15th 2013

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!



- Perverse Incentives in Age and Funding Longevity Research
- Robust Cancer Therapies Will Mean More Aggressive Stem Cell Therapies
- On Genetic Association Studies of Human Longevity
- Exercise in Mice and Men
- Neural Plasticity and the Brain's Stem Cells
- Discussion
- Latest Headlines from Fight Aging!
    - Limited Evidence for the Universality of Heat Shock Hormesis as a Way to Induce Longevity
    - Examining the Biochemistry of Arctica Islandica Longevity
    - On Intermittent Fasting
    - Engineered Stem Cells Show Promise in Heart Therapy Trial
    - Building Better Blood Vessels
    - Support for Radical Life Extension in Canadian Public Survey
    - Kidney Disease Risk is Another Reason Not to Be Overweight
    - An Example of the Evolution of Life Span
    - Considering Transposons and Neurodegeneration in Aging Flies
    - More Chimeric Antigen Receptor Based Cancer Targeting


Here is a thing to consider: as folk grow older they generally grow wealthier at the same time. There's nothing magical about this, of course. The longer you have to save and invest, the more you will have saved and invested. I'd imagine that the freedom and security that comes with not living hand to mouth or as a dependent is one of the more important reasons why older people are generally happier than younger people.

Older people also have the greatest need for the fruits of longevity science: better ways to treat age-related disease, but more importantly ways to reverse the course of aging by repairing its root causes, the various forms of low-level biochemical damage that accumulate over the years. So you might think that there is a fortunate confluence of circumstances here, in the the people who most need rejuvenation biotechnologies are also the people who have more in the way of resources that might help fund its development.

But there are perverse incentives at work here. The older you are, the less time you have to wait for the results of research and development to arrive. If you don't have decades to wait, then you are unlikely to benefit personally - unless you can write a check for a few hundred million dollars to the SENS Research Foundation and later buy yourself a couple of labs and clinics in less regulated Asia-Pacific countries to move directly to clinical application without going through the FDA or other equally hostile regulatory bodies. But most people can't do that, and there are few bold billionaires in this sense; most embody their own businesses and look little beyond them. The Elon Musk or Richard Branson of applied longevity science has yet to emerge.

So for the rest of the elder population, and from the raw self-interest point of view, there is no incentive to give meaningful sums to longevity science when the first rejuvenation therapies are, under the very best scenarios, at least twenty years away. Few people even see that possibility, offered by SENS if large-scale funding arrives soon, as most researchers in the longevity science mainstream tell the world that results are both far further out in time and will not achieve actual rejuvenation when they do arrive. So the old have diminished incentives to do anything to meaningful advance the state of research even as their bodies are constantly reminding them of their ongoing degeneration.

The young, of course, are extremely talented at ignoring the future. Humans, I should say, are extremely talented at ignoring the future - but the young don't yet have the constant nagging pain and lost-function reminders of a failing body, they are usually not on first name terms with the local medical community, and nor do they have as much in the way of money to donate to research into applied longevity science.

So the incentives founder at both ends of the human life span. You need vision if you're likely to benefit personally and selflessness if you are not, and neither of those things are as common as we'd all like them to be.


When it comes to medical procedures, everyone has their own definition of acceptable risk. Sadly we're then overruled by faceless bureaucrats at the US Food and Drug Administration (FDA) and similar government bodies - people who have only their own interests in mind, and suffer no consequences from making useful medical technologies illegal or too expensive for commercial use. Fortunately, the FDA doesn't rule the world: there are regions in which medical regulations are less onerous and therapies less costly, and these locations are only a plane flight away.

People who undertake medical tourism for stem cell therapies are demonstrating their own risk preferences: balancing the plausible expected benefits based on what is presently known of the science and the outcomes (in the absence of rigorous trials) against the cost and estimated risk. For stem cell treatments perhaps the largest inherent risk for early stage therapies is that of cancer resulting from the activities of transplanted cells. Work in the laboratory suggests that this risk is generally lower than first thought, but it still exists.

The world of cancer treatments is, meanwhile, changing profoundly, gearing up for a new generation of therapies that will displace chemotherapy and radiotherapy. Reprogramming immune cells or introducing targeted viruses and nanoparticles to seek out and kill cancer cells with few side-effects will be the standard operating procedure twenty years from now - and probably available outside the US in a decade. In early trials and the laboratory, these technologies are already showing impressive results.

Improvements in cancer treatment - leading to the introduction of robust therapies that can clear most common forms of cancer quickly and without accompanying illness - will, I think, go hand in hand with a far greater demand for and use of very aggressive stem cell treatments. Things like periodic infusions of massive numbers of immune cells cloned from a patient's own cells, done not just for people with medical conditions, but for the healthy as a beneficial preventative measure. Similarly, why boost regeneration and tissue maintenance via stem cell therapies only in the sick and the wounded? That makes sense if there is a significant risk associated with treatment, but in a world in which cancer is merely troublesome, why not make stem cell therapies a part of general health maintenance?

These are the sort of shifts in the cost-benefit picture of regenerative medicine that will emerge over the next couple of decades, driven by a growing ability to control the undesirable aspects of cellular biology, such as cancer.


A fair number of research groups worldwide are gathering and processing data in search of associations between minor genetic variations and human longevity. As for all studies of long-term human health, this a challenging process: statistics become involved, it is costly to gather data of even moderate quality, and the underlying biology is exceedingly complex. This is illustrated by the fact that comparatively few genetic associations can be validated across different study populations: if you find a genetic polymorphism with a statistically significant association with longevity in Italian lineages, the odds are very good that it won't show up in Asian populations, or even in other Italian study populations, for that matter. The range of minor variation in the human genome is very large, and it seems to be the case that there are many, many tiny genetic contributions to the way in which metabolism interacts with environment to determine natural longevity, most of which differ widely in different populations.

So while the funding lasts, this is a deep well for researchers to work on - just not one likely to produce more than knowledge for the foreseeable future. If you want actual results in terms of therapies to reverse the course of aging, then look to the programs described in the SENS research outline. The research community already knows what needs to be repaired in aged tissue, as the low-level differences between old and young tissue are well enumerated - it is the intricate, enormously complex metabolic dance of progressing from undamaged to damaged that remains an open field of work. The difference between SENS and the mainstream efforts to fully understand aging is the difference between on the one hand making the effort to rust-proof a metal surface and on the other producing a complete and detailed model of how rust progresses and interacts with metal structures at every level, from chemistry through to the physics of forces acting on structures and material strengths. The latter isn't necessary to achieve the goal of prevention once you know what rust is, and indeed will probably prove to cost far more than just preventing the rust.


The weight of scientific evidence tells use that regular moderate exercise is very beneficial; aside from calorie restriction, it is the best thing that basically healthy people can do for themselves. No presently available medical technology surpasses the benefits of exercise and calorie restriction for long term health for the vast majority of the population - which is a strange thing to be saying in the midst of modern medicine and biotechnology. Strange but nonetheless true. This is a state of affairs we'd all like to see change for the better, via the introduction of new biotechnologies of rejuvenation, therapies that can be envisaged in some detail today, and which (if research and development is well funded) lie only a few decades ahead of us.

Near enough to matter, but still out of reach. So at this point exercise and calorie restriction are all that most of us have to work with to increase the odds of you still being alive to benefit from future rejuvenation therapies. It has to be said that the odds are not going to be moved to anywhere near the degree they would if a very large amount of funding arrived at the SENS Research Foundation, thus speeding up progress towards clinical reversal of age-related degeneration, but most of us are not in a position to make that happen.

The benefits of exercise are very broad, much like those offered by calorie restriction. It impacts mechanisms and the speed of change throughout the body and the aging process. On this topic, I recently noticed a couple of papers that note two small aspects of the interaction of exercise and aging, one in mice, and one in we humans. In mouse studies, it's quite possible to show that exercise causes numerous health benefits: mice are short-lived and thus researchers can follow them all the way through their lives.

n the case of humans a research group must instead work with shorter snapshots of time, drawing data from existing populations with their quirks and histories. Given that, it is much harder to prove the degree to which exercise causes good health and slower aging versus only being associated with these line items. Causation is hard to demonstrate - but the general presumption is that the causation shown in animal studies is also operating in human ones when it comes to things like exercise and cardiovascular health in aging. Proving and then putting numbers to that presumption are the challenges.


Neural plasticity - the ability of the brain to generate new neurons and make good use of them in its circuitry - is a topic of growing interest in the research community. That adult brains continue to create and assimilate new neurons was a comparatively recent discovery, first made in the 1960s, but lacking conclusive proof until the 1990s. Unfortunately, the pace at which this happens declines with age. Neurogenesis, the creation of neurons, requires an active neural stem cell population, and as appears to be the case for all stem cell populations, those in the brain decline in their activities with age. At the high level this is generally thought to be an evolutionary adaptation related to cancer, a part of the evolved balance between maintaining tissues and suppressing those maintenance activities when cellular damage (which grows with age) raises the odds of spawning a cancer.

It is thought that there are benefits to be gained by boosting the pace at which new neurons are created in old individuals. Aims include restoring the general loss of cognitive function that occurs with aging, developing new types of treatment for the named neurodegenerative diseases, and so forth. This ties into much of the present ongoing work on stem cells and aging: why do they stop performing their tasks; do they decline in number or just stop working; what exactly are the biochemical cues involved? The answers are emerging piece by piece, probably broadly similar but different in detail for every different stem cell population. The best outcome we can hope for is that all stem cell declines are a reaction to growing levels of damage and disarray in cells and cellular machinery - and thus the development of therapies to repair that damage will lead stem cell populations to revert to youthful behaviors without the need for further intervention.


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!



Friday, April 12, 2013
Researchers here examine the published literature on hormesis via heat shock, one of the ways shown to induce modest gains in longevity in laboratory animals, and find less support for positive outcomes than was thought. This may or may not be significant - the goal for researchers, as for calorie restriction and other means of extending longevity, is to find the underlying mechanism of action and build a therapy that triggers it with minimal side-effects. So long as heat shock can be demonstrated to improve long term health and longevity under at least some conditions, then there is a mechanism to be found and exploited. "Hormesis is the response of organisms to a mild stressor resulting in improved health and longevity. Mild heat shocks have been thought to induce hormetic response because they promote increased activity of heat shock proteins (HSPs), which may extend lifespan. Using data from 27 studies on 12 animal species, we performed a comparative meta-analysis to quantify the effect of heat shock exposure on longevity. Contrary to our expectations, heat shock did not measurably increase longevity in the overall meta-analysis, although we observed much heterogeneity among studies. Thus, we explored the relative contributions of different experimental variables (i.e. moderators). Higher temperatures, longer durations of heat shock exposure, increased shock repeat and less time between repeat shocks, all decreased the likelihood of a life-extending effect, as would be expected when a hormetic response crosses the threshold to being a damaging exposure. We conclude that there is limited evidence that mild heat stress is a universal way of promoting longevity at the whole-organism level. Life extension via heat-induced hormesis is likely to be constrained to a narrow parameter window of experimental conditions."

Friday, April 12, 2013
The clam species Arctica islandica is very long-lived, reaching at least four centuries in the wild. Researchers are comparing its biochemistry with similar but shorter-lived species to see if they can pinpoint the mechanisms that lead to its exceptional longevity. Here is recent research on this topic: "The observation of an inverse relationship between lifespan and mitochondrial H2 O2 production rate would represent strong evidence for the disputed oxidative stress theory of aging. Studies on this subject using invertebrates are surprisingly lacking, despite their significance in both taxonomic richness and biomass. Bivalve molluscs represent an interesting taxonomic group to challenge this relationship. They are exposed to environmental constraints such as microbial H2 S, anoxia/reoxygenation, and temperature variations known to elicit oxidative stress. Their mitochondrial electron transport system is also connected to an alternative oxidase that might improve their ability to modulate [the reactive oxygen species (ROS) generated by mitochondria and which produce oxidative stress]. Here we compared H2 O2 production rates in isolated mantle mitochondria between the longest living metazoan - the bivalve Arctica islandica - and two taxonomically related species of comparable size. In an attempt to test mechanisms previously proposed to account for a reduction of ROS production in long-lived species, we compared oxygen consumption of isolated mitochondria and enzymatic activity of different complexes of the electron transport system in the two species with the greatest difference in longevity. We found that A. islandica mitochondria produced significantly less [of the reactive oxygen species] H2 O2 than those of the two short-lived species in nearly all conditions of mitochondrial respiration tested, including forward, reverse, and convergent electron flow. Alternative oxidase activity does not seem to explain these differences. However, our data suggest that reduced complex I and III activity can contribute to the lower ROS production of A. islandica mitochondria, in accordance with previous studies." Reduced activity within mitochondria in this sense shows up in some longevity-inducing mutations in laboratory animals. Mitochondrial activity and composition (how much damage they cause per unit time, and how resistant they are to damage) appears to be very important as a determinant of longevity differences between species. This should increase our interest in ways to repair mitochondrial damage in humans as a potential rejuvenation therapy.

Thursday, April 11, 2013
Here is a popular science article on intermittent fasting, something that extends life in mice, but which is not as well researched as calorie restriction, the gold standard for science on healthy life extension. There appears to be considerable overlap in the mechanisms involved in calorie restriction and intermittent fasting, but it's not all exactly the same when gene expression patterns are examined, to pick one example. "Many diet and exercise trends have origins in legitimate science, though the facts tend to get distorted by the time they achieve mainstream popularity. Benefits are exaggerated. Risks are downplayed. Science takes a backseat to marketing. One needn't look any further than the emerging trend of intermittent fasting for a prime example. There is indeed a large body of research to support the health benefits of fasting, though most of it has been conducted on animals, not humans. Still, the results have been promising. Fasting has been shown to improve biomarkers of disease, reduce oxidative stress and preserve learning and memory functioning. [There] are several theories about why fasting provides physiological benefits. "The one that we've studied a lot, and designed experiments to test, is the hypothesis that during the fasting period, cells are under a mild stress. And they respond to the stress adaptively by enhancing their ability to cope with stress and, maybe, to resist disease." But perhaps it isn't so much the fasting that produces health benefits, per se, as the resulting overall reduction in calorie intake (if, that is, you don't overeat on nonfasting days, which could create a caloric surplus instead of a deficit). That appears, at least, to be the case in slowing diseases such as cancer in mice. "Caloric restriction, undernutrition without malnutrition, is the only experimental approach consistently shown to prolong survival in animal models," In [a] study, mice fasted twice a week for 24 hours, but were otherwise permitted to eat at liberty. During nonfasting days, the mice overate. Overall, they did not lose weight, counteracting whatever benefits they might have seen from fasting. Intermittent fasting with compensatory overeating "did not improve mouse survival nor did it delay prostrate tumor growth," the study concluded." Equally, there are studies showing that intermittent fasting without calorie restriction does extend life in nematode worms. A lot more research is needed to bring intermittent fasting up to the level of confidence that we can have in calorie restriction.

Thursday, April 11, 2013
Modest progress is demonstrated in a recent stem cell therapy trial for heart failure, putting some ballpark numbers to the level of benefits obtained by patients in reputable overseas clinics for some years now. It is to be expected that this sort of published result will lend further support for medical tourism while these therapies remain restricted and largely unavailable in countries like the US, thanks to the heavy hand of the FDA and similar regulatory bodies. This trial also shows the scope of remaining progress yet to be achieved if the goal is complete organ repair, something that will likely prove impossible without an accompanying repair of at least some of the low-level biochemical damage of aging. Heart failure doesn't just randomly happen in the vast majority of cases - it emerges as a consequence of the accumulated damage of aging in heart tissue and other organs. "The multi-center, randomized Cardiopoietic stem cell therapy in heart failure (C-CURE) trial involved heart failure patients from Belgium, Switzerland and Serbia. Patients in the control group received standard care for heart failure in accordance with established guidelines. Patients in the cell therapy arm received, in addition to standard care, cardiopoietic stem cells - a first-in-class biotherapeutic. In this process, bone marrow was harvested from the top of the patient's hip, and isolated stem cells were treated with a protein cocktail to replicate natural cues of heart development. Derived cardiopoietic stem cells were then injected into the patient's heart. Every patient in the stem cell treatment group improved. Heart pumping function improved in each patient within six months following cardiopoietic stem cell treatment. In addition, patients experienced improved fitness and were able to walk longer distances than before stem cell therapy. "Six months after treatment, the cell therapy group had a 7 percent absolute improvement in EF (ejection fraction) over baseline, versus a non-significant change in the control group. This improvement in EF is dramatic, particularly given the duration between the ischemic injury and cell therapy. It compares favorably with our most potent therapies in heart failure.""

Wednesday, April 10, 2013
One of the major hurdles in tissue engineering is populating tissue with blood vessels sufficient to support it. This is absolutely essential to enable the growth of anything more than a tiny amount of tissue. Decellularization has proven to be a useful way to work around present limits, but that requires donor tissue in order to obtain the guiding extracellular matrix structure. When it comes to building tissue from scratch, researchers are still working on techniques to create the necessary blood vessel networks. "One of the major obstacles to growing new organs - replacement hearts, lungs and kidneys - is the difficulty researchers face in building blood vessels that keep the tissues alive. "It's not just enough to make a piece of tissue that functions like your desired target. If you don't nourish it with blood by vascularizing it, it's only going to be as big as the head of a pen." Today, biomedical researchers are taking two main approaches to growing new capillaries, the smallest blood vessels and those responsible for exchanging oxygen, carbon dioxide and nutrients between blood and muscles or organs. One group of researchers is developing drug compounds that would signal existing vessels to branch into new tributaries. These compounds - generally protein growth factors - mimic how cancerous tumor cells recruit blood vessels. The other group [is] using a cell-based method. This technique involves injecting cells within a scaffolding carrier near the spot where you want new capillaries to materialize. [Researchers] deliver endothelial cells, which make up the vessel lining and supporting cells. Their scaffolding carrier is fibrin, a protein in the human body that helps blood clot. "The cells know what to do. You can take these things and mix them and put them in an animal. Literally, it's as easy as a simple injection and over a few days, they spontaneously form new vessels and the animals' own vasculature connects to them. The adult stem cells from fat and bone marrow both work equally well. If we want to use this clinically in five to 10 years, I think it's crucial for the field to focus on a support cell that actually has some stem cell characteristics.""

Wednesday, April 10, 2013
An interesting result here, given that most surveys of the public conducted in recent years show mixed interest or a lack of interest in greatly extending healthy human life via medical biotechnology. Perhaps measurable progress in changing minds and educating the public is occurring now - and certainly such progress should speed up at some point after a slow start - but we need to see more such encouraging surveys before drawing that conclusion: "This paper explores Canadian public perceptions of a hypothetical scenario in which a radical increase in life expectancy results from advances in regenerative medicine. A national sample of 1231 adults completed an online questionnaire on stem cell research and regenerative medicine, including three items relating to the possibility of Canadians' average life expectancy increasing to 120 years by 2050. Overall, Canadians are strongly supportive of the prospect of extended lifespans, with 59% of the sample indicating a desire to live to 120 if scientific advances made it possible, and 47% of respondents agreeing that such increases in life expectancy are possible by 2050. The strongest predictors of support for radical life extension are individuals' general orientation towards science and technology and their evaluation of its plausibility. These results contrast with previous research, which has suggested public ambivalence for biomedical life extension, and point to the need for more research in this area. They suggest, moreover, that efforts to increase public awareness about anti-aging research are likely to increase support for the life-extending consequences of that research program."

Tuesday, April 9, 2013
Being overweight appears to behave much as though you are accumulating damage to your biology. The more time you spend being overweight and the more excess visceral fat tissue you carry, the greater your risk of suffering age-related conditions later in life, the greater your lifetime medical expenditures, and the shorter your life expectancy. The mechanisms that cause these effects may be largely linked to levels of chronic inflammation, which are increased by visceral fat tissue, though there are undoubtedly other things going on under the hood. "Being overweight starting in young adulthood may significantly increase individuals' risks of developing kidney disease by the time they become seniors, according to [a new study]. The findings emphasize the importance of excess weight as a risk factor for chronic kidney disease (CKD). The researchers analyzed information from the Medical Research Council National Survey of Health and Development, a sample of children born in one week in March 1946 in England, Scotland, and Wales. A total of 4,584 participants had available data, including body mass index at ages 20, 26, 36, 43, 53, and 60 to 64 years. Participants who were overweight beginning early in adulthood (ages 26 or 36 years) were twice as likely to have CKD at age 60 to 64 years compared with those who first became overweight at age 60 to 64 years or never became overweight. The link between overweight and CKD was only in part explained by taking diabetes and hypertension into account. Larger waist-to-hip ratios ("apple-shaped" bodies) at ages 43 and 53 years were also linked with CKD at age 60 to 64 years. "We estimated that 36% of CKD cases at age 60 to 64 in the current US population could be avoided if nobody became overweight until at least that age, assuming the same associations as in the analysis sample.""

Tuesday, April 9, 2013
Life span in a species is an evolved trait: if longer lives provide a competitive advantage over shorter-lived peers, then a species will tend to become longer lived over time. We humans are long-lived for our size in comparison to other mammals, and the current thinking on that is that it may have to do with our intelligence and social nature - there is a selection effect based on advantages to survival provided by the presence of post-reproductive elders in a collaborative environment. Salmon provide another example of the impact of evolution on aging, with their unusual aging process driven by levels of predation. The environment in which a species lives has a strong effect on life span. Here is an open access paper that considers another collection of fish species in which life spans evolved to adapt to differing mortality rates caused by environmental factors: "Early evolutionary theories of aging predict that populations which experience low extrinsic mortality evolve a retarded onset of senescence. [Here], we study annual fish of the genus Nothobranchius whose maximum lifespan is dictated by the duration of the water bodies they inhabit. Different populations of annual fish do not experience different strengths of extrinsic mortality throughout their life span, but are subject to differential timing (and predictability) of a sudden habitat cessation. In this respect, our study allows testing how aging evolves in natural environments when populations vary in the prospect of survival, but condition-dependent survival has a limited effect. We use 10 Nothobranchius populations from seasonal pools that differ in their duration to test how this parameter affects longevity and aging in two independent clades of these annual fishes. We found that replicated populations from a dry region showed markedly shorter captive lifespan than populations from a humid region. Shorter lifespan correlated with accelerated accumulation of lipofuscin (an established age marker) in both clades. Analysis of wild individuals confirmed that fish from drier habitats accumulate lipofuscin faster also under natural conditions. This indicates faster physiological deterioration in shorter-lived populations. [The] characterization of pairs of closely related species with different longevities should provide a powerful paradigm for the identification of genetic variations responsible for evolution of senescence in natural populations."

Monday, April 8, 2013
You might recall a recent article on transposons as a form of more aggressive genetic damage and disarray in the later stages of aging. It is unclear as to whether this is a secondary effect or whether it does in fact contribute to age-related decline at that stage; the arguments would be much the same as those made for other forms of stochastic DNA damage in aging. Here is another example of recently published research on transposons and aging: "[Researchers] showed that when the activity of a protein called Ago2 (Argonaute 2) was perturbed, so was long-term memory [in fruit flies] - which was tested using a trained Pavolvian response to smell. Since Ago2 is known to be involved in protecting against transposon activity in fruit flies, [the scientists] were compelled to look for transposons. Though transposons have been shown to be active during normal brain development, they are silenced soon afterward. The implication is that they have some functional role in development. When [the team] looked for transposons they found that there is a marked increase in transposon levels in the brain cells, or neurons, by 21 days of age in normal fruit flies. The levels were observed to increase steadily with age. These transposons, including one in particular called gypsy, were highly active, jumping from place to place in the genome. When they blocked Ago2 from being expressed in fruit flies, transposons accumulated at a much younger age. Accompanying this transposon accumulation were defects in long-term memory that mirrored those usually seen in much older flies, as well as a much-reduced lifespan. "Essentially the Ago2 knock out flies have no long-term memory by the time they are 20 days old, while normal flies have a normal long-term memory at the same age." [The researchers propose] that a "transposon storm" may be responsible for age-related neurodegeneration as well as the pathology seen in some neurodegenerative disorders. However, [the] studies so far don't address whether transposons are the cause or an effect of aging-related brain defects. "The next step will be to activate transposons by genetically manipulating fruit flies and ask whether they are a direct cause of neurodegeneration."" The challenge with this sort of research is that it's easy to exhibit reduced life span by pulling out necessary parts of an animal's biochemistry, but very hard to show that this is actually relevant to aging versus just another form of causing damage. The real test in this case would be to find a way to suppress transposons with minimal other changes to biochemistry and show extended life - or at least preserved cognitive function - as a result. That would be compelling.

Monday, April 8, 2013
Immune cells can be engineered to selectively target cancer cells for destruction via use of chimeric antigen receptors that match up with proteins that are more common on the exterior of a cancer cell. This strategy has been in the news of late with impressive successes against leukemia. Here researchers show that better results can be obtained by chaining together two marginal targets, each of which is only slightly discriminating for cancer cells if used on its own. "T cells made to express a protein called CAR, for chimeric antigen receptor, are engineered by grafting a portion of a tumor-specific antibody onto an immune cell, allowing them to recognize antigens on the cell surface. Early first-generation CARs had one signaling domain for T-cell activation. Second-generation CARs are more commonly used and have two signaling domains within the immune cell, one for T-cell activation and another for T- cell costimulation to boost the T cell's function. Importantly, CARs allow patients' T cells to recognize tumor antigens and kill certain tumor cells. A large number of tumor-specific, cancer-fighting CAR T cells can be generated in a specialized lab using patients' own T cells, which are then infused back into them for therapy. Despite promising clinical results, it is now recognized that some CAR-based therapies may involve toxicity against normal tissues that express low amounts of the targeted tumor-associated antigen. To address this issue [researchers] developed an innovative dual CAR approach in which the activation signal for T cells is physically dissociated from a second costimulatory signal for immune cells. The two CARs carry different antigen specificity - mesothelin and a-folate receptor. Mesothelin is primarily associated with mesothelioma and ovarian cancer, and a-folate receptor with ovarian cancer. [Dual] CAR T cells are more selective for tumor cells since their full activity requires interaction with both antigens, which are only co-expressed on tumor cells, not normal tissue."



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