Longevity Meme News and Commentary

Boosting Repair Mechanisms Beneficial in Alzheimer's

Fri, 03 Jul 2009 14:04:38 CST

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.

View the Article Under Discussion: http://www.sciencedaily.com/releases/2009/07/090701160557.htm
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Immune Therapy Versus Leukemia Stem Cells

Fri, 03 Jul 2009 13:40:46 CST

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."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2009-07/cp-ntt062409.php
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Collecting Cellular Junk

Thu, 02 Jul 2009 10:21:51 CST

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."

View the Article Under Discussion: http://greenlightgo.healthaliciousness.com/2009/07/01/growing-old-and-collecting-cellular-junk/
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Regenerating Salamanders and Their Blastemas

Thu, 02 Jul 2009 10:09:58 CST

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."

View the Article Under Discussion: http://www.the-scientist.com/blog/display/55809/
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An Overview of Induced Pluripotency

Wed, 01 Jul 2009 11:29:34 CST

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."

View the Article Under Discussion: http://www.technologyreview.com/printer_friendly_article.aspx?id=22832
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The Compression of Morbidity School of Thought

Wed, 01 Jul 2009 10:23:21 CST

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."

View the Article Under Discussion: http://www.technologyreview.com/printer_friendly_article.aspx?id=22954
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Longevity and Biochemical Damage Resistance

Tue, 30 Jun 2009 10:29:47 CST

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.

View the Article Under Discussion: http://dx.doi.org/10.1096/fj.08-122523
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Exercise and Neurogenesis

Tue, 30 Jun 2009 10:10:46 CST

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."

View the Article Under Discussion: http://www.uq.edu.au/news/index.html?article=18673
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Deciphering the Signals of Rheumatoid Arthritis

Mon, 29 Jun 2009 10:16:31 CST

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."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2009-06/icl-ntf062609.php
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"Minicells" as Targeting Mechanism

Mon, 29 Jun 2009 09:58:13 CST

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."

View the Article Under Discussion: http://www.nytimes.com/2009/06/29/health/research/29drug.html
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Towards Engineering and Adjusting the Immune System

Fri, 26 Jun 2009 10:48:46 CST

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."

View the Article Under Discussion: http://www.sciencedaily.com/releases/2009/06/090615161713.htm
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Near 100% Efficiency in Targeting Cells

Fri, 26 Jun 2009 10:19:43 CST

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."

View the Article Under Discussion: http://www.sciencedaily.com/releases/2009/06/090625152927.htm
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