FIGHT AGING! NEWSLETTER
January 16th 2012
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!
- SENS Foundation Academic Initiative Launches New Website
- Telomere Length in Young Finches Correlates With Life Expectancy
- Another Tissue Engineered Trachea Update
- Latest Headlines from Fight Aging!
SENS FOUNDATION ACADEMIC INITIATIVE LAUNCHES NEW WEBSITE
An update from the SENS Foundation:
"One of the numerous modestly-sized projects running under the auspices of the SENS Foundation is their Academic Initiative: helping to bring more life science undergraduate and postgraduate students into contact with the Strategies for Engineered Negligible Senescence, encourage them to become biogerontologists and build a career on the defeat of aging, and get them working on one of the many needed research projects that form the foundation of rejuvenation biotechnology. Science at the cutting edge takes place at many levels, from projects that can be funded with less than ten thousand dollars and three months of student time all the way up to the big hundred million dollar lab proposals. As biotechnology becomes ever cheaper and more capable, the number of significant projects and project components that can be funded at low cost and carried out successfully by graduate students grows larger by the month.
"The future of life science is many more smaller projects: a huge number of tasks to be accomplished, and technologies that make each individual task small in comparison to the labor that would have been required in previous decades. Advanced life science students should be out there making connections and accomplishing meaningful tasks - helping to advance the state of knowledge and biotechnology, not just learning and recapitulating. It's well within their capabilities, and, thanks to progress in technology, it's now also well within the appropriate budget. Programs like the SENS Foundation Academic Initiative will grow in number and become more important across the board in the life sciences.
"The Academic Initiative launched a new website recently:"
TELOMERE LENGTH IN YOUNG FINCHES CORRELATES WITH LIFE EXPECTANCY
Data to support a correlation that researchers have been expecting for a while - though of course it's more complex than a direct and straightforward relationship throughout life:
"Telomeres are the protective caps of repeated DNA sequences stuck onto the end of chromosomes, cut short with each cell division, but maintained by an enzyme called telomerase whose job, amongst others, is to extend telomeres by adding extra repeats. As you can imagine, this lays the groundwork for complex feedback loops, influenced by many genes, and different in different species and cell types. Telomere biology is associated with aging, and telomeres tend to shorten in some species and some tissues with both advancing age and ill health - but it's still an open field for the development of a full explanation as to exactly how and why that is the case. Of great interest is whether the erosion of telomeres is one of the few primary causes of aging, or whether it is only a secondary consequence - for example, do telomeres erode because of mitochondrial damage?
"There has been a fair amount of back and forth as to just how well telomere length can serve as a biomarker: lots of different outcomes in different studies. To some degree this was expected due to the differing behavior of telomerase in different tissues, but even so there is much to debate given the results to date. Here, a study in birds provides further food for thought by showing that telomere length varies in usefulness as a measure at different periods in life ... They found a highly significant correlation between telomere length at 25 days and life span; birds with longer telomeres lived longer. Length measured at 1 year also predicted life span, but the relationship was weaker, whereas at later time points (after 3, 4, 6, and 7 years) there was no correlation ... This might explain why previous results in humans and animals have not been consistent."
ANOTHER TISSUE ENGINEERED TRACHEA UPDATE
News from the research group that focuses on mplanting replacement tracheas built from a patient's own cells:
"Surgeons in Sweden have replaced the cancerous windpipe of a Maryland man with one made in a laboratory and seeded with the man's cells. ... 'What we did is surgically remove his malignant tumor,' Dr. Macchiarini said. 'Then we replaced the trachea with this tissue-engineered scaffold.' The Y-shaped scaffold, fashioned from nano-size fibers of a type of plastic called PET that is commonly used in soda bottles, was seeded with stem cells from Mr. Lyles's bone marrow. It was then placed in a bioreactor - a shoebox-size container holding the stem cells in solution - and rotated like a rotisserie chicken to allow the cells to soak in. After two days, it was installed in Mr. Lyles during an elaborate operation in which it was sutured to his throat and lungs. All told, the treatment cost about $450,000, Mr. Lyles said.
"Dr. Macchiarini has performed a dozen trachea transplants since 2008, but the first 10 used organs from cadavers in which all the living cells were removed, leaving behind a natural scaffold of cartilage. Donated tracheas are rare, however, and are never a perfect fit. In Mr. Lyle's case, and in the case of an Eritrean man who received a similar transplant last June and is doing well, the synthetic scaffold is made using CT scans of the existing trachea to ensure it matches precisely."
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!
LATEST HEADLINES FROM FIGHT AGING!
LOOKING FOR EVIDENCE OF INHERITED LONGEVITY IN CELLS
Friday, January 13, 2012
Researchers are examining cellular biochemistry in people who belong to long-lived families: "The offspring of nonagenarian siblings suffer less from age related conditions and have a lower risk of mortality compared to their partners. Fibroblast strains derived from such offspring in middle age show different in vitro responses to stress, more stress-induced apoptosis and less senescence when compared to strains of their partners. Aiming to find differences in cellular metabolism in vitro between these fibroblast strains, [cells were] analysed using (1)H nuclear magnetic resonance (NMR)-based metabolic footprinting. ... Strains from offspring and their partners were compared ... The ala-gln and glucose consumption were higher for fibroblast strains derived from offspring when compared to strains of their partners. Also, production of glutamine, alanine, lactate and pyroglutamic acid was found to be higher for fibroblast strains derived from offspring. In conclusion, differences in NMR-based metabolic profiles of human cells in vitro reflect the propensity for human longevity of the subjects from whom these were derived."
INVESTIGATING HOW STEM CELL TRANSPLANTS ASSIST HEALING IN THE BRAIN
Friday, January 13, 2012
Via EurekAlert!: "For years, researchers seeking new therapies for traumatic brain injury have been tantalized by the results of animal experiments with stem cells. In numerous studies, stem cell implantation has substantially improved brain function in experimental animals with brain trauma. But just how these improvements occur has remained a mystery. Now, an important part of this puzzle has been pieced together by researchers ... In experiments with both laboratory rats and an apparatus that enabled them to simulate the impact of trauma on human neurons, they identified key molecular mechanisms by which implanted human neural stem cells - stem cells that are in the process of developing into neurons but have not yet taken their final form - aid recovery from traumatic axonal injury. A significant component of traumatic brain injury, traumatic axonal injury involves damage to axons and dendrites, the filaments that extend out from the bodies of the neurons. The damage continues after the initial trauma, since the axons and dendrites respond to injury by withdrawing back to the bodies of the neurons. ... Axons and dendrites are the basis of neuron-to-neuron communication, and when they are lost, neuron function is lost. In this study, we found that our stem cell transplantation both prevents further axonal injury and promotes axonal regrowth, through a number of previously unknown molecular mechanisms. ... We identified about 400 proteins that respond differently after injury and after grafting with neural stem cells. ... a group of cytoskeleton proteins was being changed, and in particular one called alpha-smooth muscle actin, which had never been reported in the neurons before.""
REGENERATION OBSERVED IN KIDNEY PODOCYTE CELLS
Thursday, January 12, 2012
Another cell population thought to be static throughout life turns out to be capable of regeneration and renewal, given the right cues: "Damage to podocytes - a specialized type of epithelial cell in the kidney - occurs in more than 90 percent of all chronic kidney disease. Now researchers [have] uncovered an unexpected pathway that reveals for the first time how these cells may regenerate and renew themselves during normal kidney function. ... Podocytes are found only in the kidney and are an integral structural component of its blood-filtering system. They stand shoulder-to-shoulder in a part of the organ called the glomerulus and wrap their long 'feet' around the semi-permeable capillaries through which blood flows. Narrow slits between the feet allow small molecules, such as water and salts, to pass while blocking large proteins. This filtering process is the first step to forming urine, and it is critically important - even one missing cell can leave a gap that would allow unwanted molecules through the barrier. ... It used to be thought that you were born with podocytes, and you died with the same podocytes - you don't make any more during your lifetime. ... The problem was, such a scenario doesn't make a lot of evolutionary sense - particularly when other epithelial cells routinely regenerate themselves. ... Podocytes may utilize recognized pathways of regeneration to renew themselves throughout life, [and] people suffering from chronic kidney disease may simply have worn out or outpaced their podocytes' capacity for renewal ... Now that the researchers know podocytes have the ability to regenerate in response to common cellular signals, their next step is to learn whether this regeneration occurs in healthy animals and people. ... If we can harness this regeneration, we may one day be able to treat people with chronic kidney disease."
FROM THE PROGRAMMED AGING CAMP
Thursday, January 12, 2012
Here is an open access paper from a researcher who focuses on mTOR and sees aging as almost entirely programmed, not the consequence of stochastic damage. His view as outlined in the paper is analogous to the view of nuclear DNA damage as not being significant over the present human life span. I think he has a very large hill of evidence for the damage-based view of aging to overcome in order to make a convincing point, however, and this should serve as a reminder that there are a great many diverse (but not necessarily well supported) views in the scientific community when it comes to the nuts and bolts of aging: "Aging is defined as a decline caused by accumulation of all sorts of damage, in particular, molecular damage. This statement seemed so obvious that it was not questioned. Yet several lines of evidence rule out molecular damage as a cause of aging. Yes, of course, molecular damage accumulates over time. But this accumulation is not sufficient to cause organismal death. Eventually it would. But the organism does not live long enough, because another cause terminates life first. This cause is aging, a continuation of developmental growth. Definitely, developmental growth is not driven by accumulation of molecular damage, although molecular damage accumulates. Similarly, aging is not driven by damage. Growth is stimulated in part by mitogen- and nutrient-sensing (and other) signaling pathways such as mTOR. Aging, 'an aimless continuation of developmental program', is driven by the same signaling pathways including mTOR. Aging in turn causes damage: not molecular damage but non-random organ damage (stroke, infarction, renal failure and so on) and death. Seemingly, one objection to this concept is that cancer is caused by molecular damage. And cancer is often a cause of death in mammals. So how may one claim that damage does not drive aging, if it is involved in cancer. Let us discuss this."
DISCUSSING TAU VACCINES AT THE SENS FOUNDATION
Wednesday, January 11, 2012
The latest in a series of articles on immunotherapies aimed at clearing out the build up of cellular aggregates involved in Alzheimer's disease: "Immunotherapy targeting the age-related accumulation of extracellular aggregates, in the form of ß-amyloid, is the first rejuvenation biotechnology to reach Phase III human clinical trials. The promise of this therapy for the treatment and prevention of Alzheimer's disease (and ultimately, of so-called 'normal' brain aging) has sparked an interest in utilizing the same approach for other forms of aging damage, including the clearance of aggregated intracellular proteinaceous aging damage. Notably, as we have reviewed in a series of four previous posts, recent years have seen the appearance of a rising number preclinical studies of therapeutic vaccines targeting pathological tau species accumulating in the brains and spinal cords of transgenic rodent models of tauopathic neurodegeneration. These studies have reported -- somewhat surprisingly -- the antibody-mediated clearance of these primarily intracellular aging lesions, accompanied by functional improvements in treated animals. These two forms of structural damage are major contributors to the age-related degeneration of the brain, whether it leads to frank dementia or to the diagnostic euphemism of 'normal' age-related cognitive decline, and novel therapeutics to effect the removal of both from aging neurons will be key elements of a comprehensive panel of rejuvenation biotechnologies."
DAVID BRIN ON THE URGE TO RADICAL LIFE EXTENSION
Wednesday, January 11, 2012
Via the IEET: "Suppose you had a chance to question an ancient Greek or Roman - or any of our distant ancestors, for that matter. Let's say you asked them to list the qualities of a deity. It's a pretty good bet that many of the 'god-like' traits he or she described might seem trivial nowadays. After all, we think little of flying through the air. We fill pitch-dark areas with sudden lavish light, by exerting a mere twitch of a finger. Average folks routinely send messages or observe events taking place far across the globe. Copious and detailed information about the universe is readily available through crystal tubes many of us keep on our desks and command like genies. Some modern citizens can even hurl lightning, if we choose to annoy our neighbors and the electric company. Few of us deem these powers to be miraculous, because they've been acquired by nearly everyone in prosperous nations. After all, nobody respects a gift if everybody has it. And yet, these are some of the very traits that earlier generations associated with divine beings. Even so, we remain mortal. Our obsession with that fate is as intense as it was in the time of Gilgamesh. Perhaps more, since we overcame so many other obstacles that thwarted our ancestors. Will our descendants conquer the last barriers standing between humanity and Olympian glory? Or may we encounter hurdles too daunting even for our brilliant, arrogant, ingenious and ever-persevering species? ... Here's the safest prediction for the next 100 years - that mortality will be a major theme. Assuming we don't blow up the world, or fall into some other catastrophic failure mode, human beings will inevitably focus on using advanced technology to cheat death."
COGNITIVE FUNCTION DECLINE WITH AGING CAN START EARLY
Tuesday, January 10, 2012
The decline of the brain is all the more reason to work harder on rejuvenation biotechnology and make better lifestyle choices: "researchers found a 3.6% decline in mental reasoning in women and men aged 45-49. They assessed the memory, vocabulary and comprehension skills of 7,000 men and women aged 45 to 70 over 10 years. ... Previous research had suggested that cognitive decline does not begin much before the age of 60. But the results of this study show that it could in fact begin in middle age. This is important, the researchers say, because dementia treatments are more likely to work at the time when individuals start to experience mental impairment. The results of the tests show that cognitive scores declined in all categories except vocabulary - and there was a faster decline in older people. The study found a 9.6% decline in mental reasoning in men aged 65-70 and a 7.4% decline for women of the same age. ... We now need to look at who experiences cognitive decline more than the average and how we stop the decline. Some level of prevention is definitely possible. Rates of dementia are going to soar and health behaviours like smoking and physical activity are linked to levels of cognitive function. It's important to identify the risk factors early. If the disease has started in an individual's 50s but we only start looking at risk in their 60s, then how do you start separating cause and effect? ... Previous research suggests that our health in mid-life affects our risk of dementia as we age, and these findings give us all an extra reason to stick to our New Year's resolutions. Although we don't yet have a sure-fire way to prevent dementia, we do know that simple lifestyle changes - such as eating a healthy diet, not smoking, and keeping blood pressure and cholesterol in check - can all reduce the risk of dementia."
AN EXAMPLE OF A TARGETED CANCER THERAPY
Tuesday, January 10, 2012
The important portion of a targeted therapy for killing cells - cancer cells in this case - is not the part that destroys the cell itself. Any old chemotherapy drug can be used to that end. The point of the targeting mechanism is that the drug can be delivered in tiny, precise doses to minimize side-effects and any harm to surrounding tissues. These technologies are well worth watching because they will have far broader applications than just cancer. There are many areas in the aging body where targeted cell destruction will do a great deal of good, such as senescent cells and portions of the immune system. Here is an example from the cancer research community: "The process involved is akin to building and equipping a car with the finest features, adding a passenger (in this case the cancer drug), and sending it off to its destination (in this case the cancer cell). To design the 'vehicle,' researchers used a selection strategy developed by Farokhzad's team that allowed them to essentially select for ligands (molecules that bind to the cell surface) that could specifically target prostate cancer cells. The researchers then attached nanoparticles containing chemotherapy, in this case docetaxel, to these hand-picked ligands. To understand Farokhzad's selection strategy, one must understand ligand behavior. While most ligands mainly have the ability to bind to cells, the strategy of Farokhzad and his colleagues allowed them to select specific ligands that were not only able to bind to prostate cancer cells, but also possessed two other important features: 1) they were smart enough to distinguish between cancer and non-cancer cells and 2) they were designed to be swallowed by cancer cells. ... Most ligands are engulfed by cells, but not efficiently. We designed one that is intended to be engulfed."
IDENTIFYING GENES THAT CONTROL CELL MAINTENANCE
Monday, January 9, 2012
The processes that keep cells clear of debris and otherwise well maintained are important in aging - what we know of autophagy should make that clear. Here, researchers are taking a brute force approach to enumerating the controlling mechanisms of cellular homeostasis: "To do its job properly within the cell, a protein first must fold itself into the proper shape. If it doesn't, trouble can result. More than 300 diseases have at their root proteins that misfold, aggregate and eventually cause cellular dysfunction and death. [The] research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development. ... These discoveries are exciting because we have identified genes that keep us healthy and small molecules that keep us healthy. Future research should explain how these two important areas interact. ... [Researchers] tested all of the approximately 19,000 genes in C. elegans. They reduced expression of each gene one at a time and looked to see if the gene suppressed protein aggregation in the cell. Did the gene increase aggregation or lessen it or have no effect at all? The researchers found 150 genes that did have an effect. They then conducted a series of tests and zeroed in on nine genes that made all proteins in the cell healthier. ... These nine genes define a core homeostastis network that protects the animal's proteome (the entire set of proteins expressed by the organism) from protein damage. ... These are the most important genes. Figuring out how nine genes - as opposed to 150 - work is a manageable task."
REVERSING AGE-RELATED LOSS OF MYELIN REPAIR
Monday, January 9, 2012
Via EurekAlert!: researchers "have found that the age-related impairment of the body's ability to replace protective myelin sheaths, which normally surround nerve fibers and allow them to send signals properly, may be reversible, offering new hope that therapeutic strategies aimed at restoring efficient regeneration can be effective in the central nervous system throughout life. ... Using a surgical technique, the researchers introduced an experimental demyelinating injury in the spinal cord of an old mouse, creating small areas of myelin loss, and then exposed those areas to cells found the blood of a young mouse. By doing so, they found that the influx of certain immune cells, called macrophages, from the young mouse helped resident stem cells restore effective remyelination in the old mouse's spinal cord. This 'rejuvenating' effect of young immune cells was mediated in part by the greater efficiency of the young cells in clearing away myelin debris created by the demyelinating injury. Prior studies have shown that this debris impedes the regeneration of myelin. ... Aging impairs regenerative potential in the central nervous system. This impairment can be reversed, however, suggesting that the eventual development of cell-based or drug-based interventions that mimic the rejuvenation signals found in our study could be used therapeutically."