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We help you stay up to date with the most interesting news in medicine, politics and the healthy life extension community. You can help us by contacting us when you see interesting items online. You can search past news postings through Google by using the form to the right.
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| One might expect that improving repair and maintenance systems in the brain would provide some benefit irrespective of how present damage came about, and this may be the case: "The granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer's mice ... The growth factor prodded bone-marrow derived microglia outside the brain to join forces with the brain's already-activated microglia in eliminating the Alzheimer's protein from the brain. Microglia are brain cells that act as the central nervous system's main form of immune defense. Like molecular 'Pac-men,' they rush to the defense of damaged or inflamed areas to gobble up toxic substances." This is still a rearguard action against end-stage consequences, however - the underlying chain of causes is not addressed. Repair of final consequences isn't a viable long-term strategy for dealing with an ever-worsening root cause, as those consequences will rapidly exceed the ability to repair them. At some point you have to address the origin of the problem in order to prevent it from spiraling out of control. |
| Via EurekAlert!, an example of progress in using the immune system to target specific cells for destruction: acute myeloid leukemia (AML) "is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy. ... The cellular and molecular basis for this dismal picture is unclear. However, previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance ... [researchers] exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells. CD123 is part of the interleukin-3 receptor, a protein that interacts with a growth factor (called a cytokine) that influences cell survival and proliferation. The researchers created a therapeutic antibody that recognized and bound to CD123 with the hope that this antibody would selectively interfere with AML-LSC survival. When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signaling in the tumor cells was blocked. Further, 7G3 impaired migration of the AML-LSCs to bone marrow and activated the innate immune system of the host mouse to destroy the AML-LSCs. Overall, treatment with 7G3 substantially improved mouse survival." |
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| Newer longevity science blog Green Light Go here looks at the harmful accumulation of metabolic byproducts and other junk such as lipofuscin in our cells with age: "I just finished an entry for the SOA timeline on the 1970s discovery that nematodes collect inactive enzymes and molecules as they grow older. The main idea being that the body is unable to clear out the junk inside cells and that the energy cost of carrying this junk leads to senescence, or aging. The theory reminded me of a similar finding by Coleen Murphy who found that long lived daf-16 elegans mutants lived longer in part because they encoded antimicrobial lysosomes, that helped to clear out microbes that would get "packed" inside the nematodes precipiating senescence and eventually their death. As far as I know, the reason for the slow decline in enzyme activity and for the collection of intracellular junk is still unknown. Why isn't our body clearing this stuff out and selling it on ebay? The SENS foundation, which is perhaps the biggest player in anti-aging research, is pushing forward with a solution anyway. Their strategy is to find enzymes manufactured by soil bacteria and fungi that can then be applied therapeutically to help clear junk out of cells. ... It is going to be interesting in the future to see what result comes of this. Both for understanding the chemical mechanism of the collection of junk, and the therapeutic solutions which can get rid of it." |
| Progress in understanding the mechanisms by which salamaders regenerate lost limbs from The Scientist: "The cells responsible for the salamander's famed ability to regenerate amputated limbs aren't pluripotent, as scientists have thought ... They're retaining their memory of the tissues they came from, and they go on to form cells of that same type. That's not what most people thought was going on ... That's good news for regenerative medicine: If the mechanism salamander cells use for regrowing body parts doesn't depend on pluripotent stem cells, it may be easier than researchers have assumed to mimic that organism's regenerative strategy in potential therapies. ... Salamanders' regenerative abilities were thought to rely on the dedifferentiation of cells near the damaged limb to a pluripotent state -- a feat that mammalian cells are normally incapable of. ... Instead of trying to generate multipotent or pluripotent cells, [researchers] should try to understand how these cells get the appropriate signals to make a new limb in terms of organizing the different tissue types." |
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| The Technology Review here looks at the technology of induced pluripotency: "Scientists have been talking about the medical promise of stem cells for more than a decade, even before human embryonic stem cells were successfully isolated in 1998. Most of the public attention has focused on their regenerative power: since stem cells can renew themselves and differentiate into specialized cell types, they could potentially be used to build replacement organs, heal spinal-cord injuries, or repair damaged brain tissue. But the research world has also pursued another, even broader-reaching goal: using the cells of patients with various illnesses to derive pluripotent stem cells, which can give rise not just to the specialized cells in a particular organ or tissue but to virtually any cell type. Those cells could be used to create laboratory models of disease. For example, a cell from a Parkinson's patient could be turned into a neuron, which would exhibit the progressive molecular changes at work in the neurodegenerative disorder. This type of tool could capture the details of human disease with unprecedented accuracy, and it could revolutionize the way researchers search for new treatments." |
| This interview with Leonard Hayflick is illustrative of the thinking of gerontologists who aim not to extend human life (in this case because because he thinks it's an implausible goal) but to shorten the period of age-related disability. It's a view very much at odds with reliability theory, which suggests that any reduction in ongoing damage will extend healthy life, and with the many demonstrated extensions of lifespan in animals. "The facts are these. There are four aspects to the finitude of life: aging, longevity determination, age-associated diseases, and death. Aging is what we call a catabolic process - the breakdown of molecules. Longevity determination is the reverse - the repair or maintenance of molecules. Aging gets confused with longevity determination. The aging process increases vulnerability to age-associated diseases. These concepts are distinguishable from each other and fundamentally different. ... You cannot learn about the fundamental biology of aging by studying disease processes. Resolving age-associated diseases tells us nothing about the fundamental biology of aging, just as the resolution of childhood diseases, such as polio and childhood anemia, did not tell us one iota about childhood development." |
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| Why do some mammal species live much longer than other, very similar mammal species? Here researchers look at resistance to biochemical damage: "Altered structure, and hence function, of cellular macromolecules caused by oxidation can contribute to loss of physiological function with age. Here, we tested whether the lifespan of bats, which generally live far longer than predicted by their size, could be explained by reduced protein damage relative to short-lived mice. We show significantly lower protein oxidation (carbonylation) in Mexican free-tailed bats (Tadarida brasiliensis) relative to mice, and a trend for lower oxidation in samples from cave myotis bats (Myotis velifer) relative to mice. Both species of bat show in vivo and in vitro resistance to protein oxidation under conditions of acute oxidative stress. These bat species also show low levels of protein ubiquitination in total protein lysates along with reduced proteasome activity, suggesting diminished protein damage and removal in bats. ... Together, these data suggest that long lifespan in some bat species might be regulated by very efficient maintenance of protein homeostasis." You might take a moment to compare this with research into naked mole rat biochemistry. |
| Another benefit of regular exercise is proposed in this recent research: scientists "have, for the first time, been able to demonstrate that moderate exercise significantly increases the number of neural stem cells in the ageing brain. ... neuroscientists have known for some time that, in healthy brains, the creation of new neurons is an ongoing and lifelong mechanism. However, it has also been known for more than a decade that the number of new neurons we produce slowly declines with age. ... Investigating the mechanism by which neural stem cell numbers are altered will undoubtedly increase our understanding of how the brain responds to its environment. Ultimately, this should allow us to discover how to harness the brain's regenerative capacity, and to bring about new and effective treatments for conditions caused by trauma, disease, or even normal ageing. The brain's ability, even at an advanced age, to respond in a positive manner is very exciting as it extends the time-frame in which manipulation is possible." |
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| Researchers continue to work towards identifying the exact molecular mechanisms by which autoimmune conditions like rheumatoid arthritis produce pain and damage: "When a microbe infects the body, the body responds by turning on a molecular switch to set the immune system into action and protect the body from disease. Today's findings show that a signal molecule called tenascin-C can trigger the same molecular switch and also activate the immune system. High levels of tenascin-C present in joints therefore may cause the activated immune system to attack the joint leading to the persistent inflammation of rheumatoid arthritis. The molecular switch is called TLR4, and is found on the surface of immune cells. Previous research has shown that mice without TLR4 do not show chronic joint inflammation. The researchers hope scientists can develop new treatments that target the interaction between tenascin-C and TLR4, which may help to combat rheumatoid arthritis. ... We hope our new findings can be used to develop new therapies that interfere with tenascin-C activation of the immune system and that these will reduce the painful inflammation that is a hallmark of this condition." |
| Effective per-cell-type targeting of therapies is a fundamental and very important technology platform for the future of medicine. Here's another way of doing it, distinct from methods using viruses or nanoparticles: "The minicells are generated from mutant bacteria which, each time they divide, pinch off small bubbles of cell membrane. The minicells can be loaded with chemicals and coated with antibodies that direct them toward tumor cells. No tumor cell, so far as is known, produces a specific surface molecule for toxins to act on. But 80 percent of solid tumors have their cell surfaces studded with extra-large amounts of the receptor for a particular hormone, known as epidermal growth factor. The minicells can be coated with an antibody that recognizes this receptor, so they are more likely to attach themselves to tumors than to the normal cells of the body. The tumor cells engulf and destroy the minicells, a standard defense against bacteria, and in doing so are exposed to whatever cargo the minicells carry. ... treatment arrested tumor growth in mice implanted with either human colon or human breast tumors, and enabled mice with drug-resistant human uterine tumors to eliminate the tumors altogether." |
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| This ScienceDaily release gives some insight into how we might manipulate and repair our aging immune systems in the near future: "During their development in the thymus gland, a kind of 'T-cell school', every T-cell is fitted out with its own personal receptor. The diversity of these receptors allows the immune system to respond to nearly all pathogens. Since T-cell receptors are all randomly constructed, there is also a constant production of T-cells in the thymus that may recognize and attack the body's own structures. ... Most of these dangerous autoreactive T-cells, though, are sorted out in a screening process before they leave the thymus ... But not all autoreactive T-cells are driven to cell death. Some of them are 'reeducated' into so-called regulatory T-cells. While these still possess a T-cell receptor that targets the body's own structures, they have been reprogrammed during their development in the thymus so that they can no longer cause any damage. In fact, it is [quite the opposite]. ... They even keep other nearby errant T -cells under control. This is why the mechanisms for the creation of regulatory T-cells are of enormous practical interest. Deciphering these processes could lead to new therapeutic approaches for autoimmune diseases such as multiple sclerosis, rheumatic arthritis and type-1 diabetes, which are triggered by autoreactive T-cells." |
| Being able to target very specific cell populations by their distinctive surface chemistry is fundamental to the next generation of medical technologies: "It is now possible to engineer tiny containers the size of a virus to deliver drugs and other materials with almost 100 percent efficiency to targeted cells in the bloodstream. ... We can introduce just about any drug or genetic material that can be encapsulated, and it is delivered to any circulating cells that are specifically targeted ... The technique involves filling the tiny lipid containers, or nanoscale capsules, with a molecular cargo and coating the capsules with adhesive proteins called selectins that specifically bind to target cells. A shunt coated with the capsules is then inserted between a vein and an artery. Much as burrs attach to clothing in a field, the selectin-coated capsules adhere to targeted cells in the bloodstream. ... [For example], metastasizing cancer cells circulating in the blood stream can stick to selectin-coated devices containing a second protein that programs cancer cells to self-destruct." |
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| Researchers here investigate the effects of a mouse longevity gene, and see that it promotes a better functioning thymus and immune system in old age: "Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). ... deletion of PAPPA in mice leads to lifespan extension. ... Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA(-/-) mice maintain [a thymus] densely populated by [thymocytes] that are capable of differentiating into single-positive CD4 and CD8 T cells. ... PAPPA(-/-) mice have an overall larger pool of naive T cells ... old PAPPA(-/-) mice have significantly lower prevalence of [T cell forms] known to inhibit T cell activation with normal aging. ... These data suggest [a relationship between IGF and the immune system in healthy longevity]. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to [maintain the immune system during] aging." Reversing the decline of the aging immune system is an important step in prolonging healthy life; the more potential strategies on the table, the better off we are. |
| For a field to move efficiently towards its end goal, there has to be some money-making application for early results and partial advances. Here's a look at early applications of work towards artificial bioengineered organs: "Our artificial organ systems are aimed at offering an alternative to animal experiments ... Particularly as humans and animals have different metabolisms. 30 per cent of all side effects come to light in clinical trials ... The special feature, in our liver model for example, is a functioning system of blood vessels. This creates a natural environment for cells. We don't build artificial blood vessels for this, but use existing ones - from a piece of pig's intestine. ... All of the pig cells are removed, but the blood vessels are preserved. Human cells are then seeded onto this structure - hepatocytes, which, as in the body, are responsible for transforming and breaking down drugs, and endothelial cells, which act as a barrier between blood and tissue cells. ... The researchers established that the cells work in a similar way to those in the body. They detoxify, break down drugs and build up proteins. These are important pre-conditions for drug tests or transplants, as the effect of a substance can change when transformed or broken down - many drugs are only metabolized into their therapeutic active form in the liver, while others can develop poisonous substances." |
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| Much of medicine might be thought of, crudely, as the quest to control our cells - to influence their actions and alter their mechanisms to obtain beneficial results. Use of chemicals is the predominant methodology, but it's not the only path forward, as is illustrated here: "Many patients spontaneously recover some function in the weeks and months after suffering a stroke, as their brains reorganize to compensate for the damaged area. Scientists are searching for ways to both boost and focus this innate plasticity, thus improving neural repair. Electrical activity is one option under study: electrical current applied to the brain can modulate brain-cell activity - a crucial component of neural remodeling. ... A week after the start of the experiment, patients given the real treatment performed much better on a number of motor tests [than] those who received the fake treatment, improving by about 12 to 15 percent versus about 3 to 5 percent." This is analogous to early drug development: discovery by experiment, crude usage and small benefits. But we could envisage a line of science that made much more precise use of electromagnetic stimulation in concert with the new tools and knowledge of biotechnology. Would it be practical and competitive with other forms of medicine? Maybe, maybe not. But a great breadth of methodologies in research is the best sign that progress lies ahead. |
| The weight of evidence indicates exercise to be beneficial to healthy longevity. This would be expected in most species for much the same evolutionary reasons that calorie restriction extends longevity in almost all species. But how do you test that? "Declining mobility is a major concern, as well as a major source of health care costs, among the elderly population. Lack of mobility is a primary cause of entry into managed care facilities, and a contributing factor to the frequency of damaging falls. Exercise-based therapies have shown great promise in sustaining mobility in elderly patients, as well as in rodent models. ... Here, we describe the first exercise-training paradigm in an invertebrate genetic model system. Flies are exercised by a mechanized platform, known as the Power Tower ... When young flies are subjected to a carefully controlled, ramped paradigm of exercise-training, they display significant reduction in age-related decline in mobility and cardiac performance. Fly lines with improved mitochondrial efficiency display some of the phenotypes observed in wild-type exercised flies. ... The development of an exercise-training model in Drosophila melanogaster opens the way to direct testing of single-gene based genetic therapies for improved mobility in aged animals, as well as unbiased genetic screens for loci involved in the changing response to exercise during aging." |
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| This open access paper uses historical data to argue that differences in human mitochondrial DNA (mtDNA) lead to differing health and longevity benefits in response to calorie restriction: "We chose to focus on haplogroup H, which is one of the more recent haplogroups, but also now the most prevalent European mtDNA haplogroup, and compare historical longevity in closely related haplogroup U individuals under extremes of caloric intake. ... The human population has undergone dramatic shifts in caloric intake during different time periods throughout the last 200 years. ... We see an expected general increase in longevity during the 20th century in both haplogroups. Before 1920 there is no significant difference between the longevity of individuals in haplogroup H and U. During the caloric restriction of the Great Depression, 1920-1940, haplogroup H shows significant increase in longevity compared to haplogroup U [with a] mean difference [of] 2.6 years." A very clever analysis; the researchers go on to use computer modeling to theorize on how a specific single nucleotide polymorphism difference between the haplogroups produces this longevity difference. |
| While very interesting advances are taking place in stem cell laboratories, the immediate applications of stem cells to therapy largely involve transplants. So newly discovered sources of stem cells for transplant are likely to be employed for some years to come. Here, ScienceDaily notes the researchers have found "a new avenue for harvesting stem cells from a woman's placenta, or more specifically the discarded placentas of healthy newborns. The study also finds there are far more stem cells in placentas than in umbilical cord blood, and they can be safely extracted for transplantation. Furthermore, it is highly likely that placental stem cells, like umbilical cord blood and bone marrow stem cells, can be used to cure chronic blood-related disorders such as sickle cell disease, thalassemia, and leukemia. ... The greater supply of stem cells in placentas will likely increase the chance that an HLA (human leukocyte antigen) matched unit of stem cells engrafts, making stem cell transplants available to more people. The more stem cells, the bigger the chance of success." |
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| People should be free to do stupid things with their own property, including their own bodies. Similarly people should be free to persuade, catcall, and debate when dumb courses of action are undertaken by others. Here, the American Medical Association (AMA) reminds us of the present state of scientific knowledge on hormone therapies: "Despite the widespread promotion of hormones as anti-aging agents by for-profit Web sites, anti-aging clinics and compounding pharmacies, the scientific evidence to support these claims is lacking ... People want a fountain of youth, and it doesn't exist. You need to conduct trials which prove the efficacy and safety of these products as you would with any other medication." Though what the AMA (and FDA) regard as sufficient trials are in fact so onerous as to be destructive of progress, a regulatory burden that blocks useful innovations and dramatically raises the cost of others. When listening to organizations like the AMA, keep in mind that they operate as a guild - their goal is to maintain high barriers to entry to their professional space so as to keep prices high. Regardless of the politics here, a weight of evidence for hormone therapies just doesn't exist, however. Despite the loud "anti-aging" marketplace, these therapies remain proven useful only for a small range of rather unpleasant diseases. |
| You'll find plenty of healthy debate in the aging research community: "Currently, the Oxidative Stress (or Free Radical) Theory of Aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited ... Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice." Or suggests that the antioxidant processes examined aren't particularly important to longevity. The best counterpoint to the paper's thesis I know of is the demonstrated use of mitochondrially targeted antioxidants to extend life span in mice. |
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