Longevity Meme Newsletter, August 30 2010

August 30 2010

The Longevity Meme 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 the Longevity Meme.



- A Look at Mitochondrial Repair Research
- Longevity in the 21st Century
- Hazy on the Topic of Aging
- Discussion
- Latest Healthy Life Extension Headlines


Mitochondria are the cell's power plants, and the damage they accumulate with advancing age is a significant component of age-related degeneration. But methods of repair are on the horizon, some already demonstrated in animals in the laboratory:


"Mitochondria were once symbiotic bacteria, way back in the dim and distant evolutionary past, and one remnant of that origin is that they contain their own DNA, separate from the DNA within the cellular nucleus. Unfortunately for us, the operating processes of mitochondria gradually damage their DNA, which in turn leads to a chain of consequences and further cellular damage, spreading and accelerating over the years to produce a large faction of what we know as degenerative aging. Aging is nothing more than accumulated biochemical damage, and our mitochondria produce more than their fair share of that damage.

"You will recall that DNA is essentially a blueprint for proteins, and that the proteins produced from these blueprints through the process of gene expression are components in biological machinery vital to the operation of a cell - or of a mitochondrion. If a section of mitochondrial DNA is knocked out by damage, then that mitochondrion is no longer capable of full functionality. It can no longer produce one or more of the proteins it needs, a state of affairs which causes all sorts of issues.

"If, however, scientists could employ modern biotechnology to repair or work around mitochondrial DNA damage and the consequent loss of important proteins, then the medical community could build a therapy to completely alleviate this aspect of aging. We know that it takes a few decades of life for the effects of accumulated mitochondrial DNA damage to even start to become significant (given that most thirty year olds are in good shape), so a repair therapy for mitochondria would only have to be applied once every twenty or thirty years at worst."


A recent presentation by demographic researchers Leonid Gavrilov and Natalia Gavrilova can be found in PowerPoint format:


"The presentation is a good overview of presently established trends and viewpoints held in the mainstream of medical research. In essence, present trends lead to only modest gains in human life span if extrapolated - but extrapolation, always a dangerous undertaking, is particularly foolhardy in these early years of the biotechnology revolution. ... the technologies that may lead to radical extension of the healthy human life span - such as realization of the Strategies for Engineered Negligible Senescence - are the most uncertain in terms of timing. The present pace of research is both rapid and unpredictable, and so is the time it will take for new paradigms of longevity science to become dominant in large research communities. The story of longevity in the 21st century is one of great unpredictability - but the flip side of that pronouncement is that the future is open to change. The more we do now to accelerate research and advocate longevity science, the sooner we'll see results."


You'll find a commentary by Aubrey de Grey in the latest issue of Rejuvenation Research, in which he notes that there is still much to be done in turning the scientific community to a productive view of aging and engineered longevity:


"Most nonbiologists, and even quite a few biologists, are spectacularly hazy on the topic of how aging relates to the diseases of old age. The prevailing biogerontological approach has long been that aging is not a disease, or at best that it predisposes to disease. Regular readers will know I'm not going to agree with that, and that I view it as axiomatic that aging is the set, progressive early stages of the various age-related diseases, without which they simply could not be age-related. But whatever one's view, it should be clear that maintenance of that traditional rhetoric will continue to limit the amount of public funding that will be spent on productive aging research, and to completely scupper the argument that some of the money spent on those diseases could very profitable be spent on postponing aging by repairing the progressive early stages of disease.

"It remains unclear when, and how, the transition to a simple and compelling description of biomedical gerontology - as, for example, 'preventative geriatrics' - will finally occur, but it certainly has not occurred yet, and the result is that the potential for intervention in aging to address the diseases and disabilities of old age remains vastly underrecognized in the funding policies of the nations that lead biomedical research."


The highlights and headlines from the past week follow below.

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From Nature: "A model published this week questions a popular theory dubbed the 'grandmother hypothesis', which says that human females, unlike those of the other great apes, survive well past their reproductive prime because of the benefits that post-menopausal women offer to their grandchildren. ... Chimps almost never live into their forties in the wild, but most humans, if they're lucky enough to make it to adulthood, live beyond the childbearing years. ... Despite its anecdotal support and intuitive appeal, the grandmother hypothesis lacked much quantitative proof showing that it was possible for longevity to evolve from grandmothering ... [Researchers] ran a mathematical simulation to test the theory's plausibility. Their agent-based model, which simulates the actions and interactions of individuals, begins with a population of 1,000 people whose lifespans and reproductive windows are an inherited trait that mutates over time. ... After about 500 generations, the model demonstrated that the assistance of a grandmother during infancy shortened the interval between the times their daughters give birth, and led to shorter reproductive windows. However, compared with simulations in which grandmothers did not help out, the benefits never result in a change in longevity. ... In hindsight [the] result isn't as surprising at it might seem. Natural selection is strongest early in life, and its influence on a trait wanes as an organism ages. Therefore, the benefits of grandmothering would have to be enormous to extend human lifespan."

A post on autophagy at Metamodern: "I’d like to say a few words about one of the hottest and, in my view, most important areas in biomedicine: autophagy, a process crucial to health, disease, and aging. Autophagy research is expanding rapidly. In autophagy ('self eating'), cells engulf and digest their own macromolecules and organelles. Autophagy serves two functions: providing critical nutrients in times of scarcity, and recycling damaged cellular structures. ... It seems that lab animals and human beings fed ad-libitum do too little autophagic recycling. The resulting accumulation of damaged machinery causes a wide range of functional deficits, and accumulation of damaged mitochondria, in particular, increases the production of reactive oxygen species, accelerating further damage. In a range of organisms, dietary restriction both induces autophagy and results in wide-ranging health benefits, including the extension of healthy lifespans. Blocking autophagy blocks the most important of these effects. Rapamycin induces autophagy and extends lifespan, as does sirtuin-1. Autophagy again appears to be central to these effects. A recent review article examines genetic interventions that indicate 'tight connections between autophagy, health span and aging'."

Work on artificial replacements for damaged corneas is showing promise: "A new study from researchers in Canada and Sweden has shown that biosynthetic corneas can help regenerate and repair damaged eye tissue and improve vision in humans. ... Globally, diseases that lead to clouding of the cornea represent the most common cause of blindness. More than a decade ago, [researchers] began developing biosynthetic corneas in Ottawa, Canada, using collagen produced in the laboratory and moulded into the shape of a cornea. ... Together, they initiated a clinical trial in 10 Swedish patients with advanced keratoconus or central corneal scarring. Each patient underwent surgery on one eye to remove damaged corneal tissue and replace it with the biosynthetic cornea, made from synthetically cross-linked recombinant human collagen. Over two years of follow-up, the researchers observed that cells and nerves from the patients' own corneas had grown into the implant, resulting in a 'regenerated' cornea that resembled normal, healthy tissue. Patients did not experience any rejection reaction or require long-term immune suppression, which are serious side effects associated with the use of human donor tissue. The biosynthetic corneas also became sensitive to touch and began producing normal tears to keep the eye oxygenated. Vision improved in six of the ten patients, and after contact lens fitting, vision was comparable to conventional corneal transplantation with human donor tissue."

Cellular reprogramming progresses: "Because liver cells (hepatocytes) cannot be grown in the laboratory, researching liver disorders is extremely difficult. However, today's new research [demonstrates] how to create diseased liver-like cells from patients suffering from a variety of liver disorders. By replicating the organ's cells, researchers can not only investigate exactly what is happening in a diseased cell, they can also test the effectiveness of new therapies to treat these conditions. It is hoped that their discovery will lead to tailored treatments for specific individuals and eventually cell-based therapy - when cells from patients with genetic diseases are 'cured' and transplanted back. Additionally, as the process could be used to model cells from other parts of the body, their findings could have implications for conditions affecting other organs. ... the scientists took skin biopsies from seven patients who suffered from a variety of inherited liver diseases and three healthy individuals (the control group). They then reprogrammed cells from the skin samples back into stem cells. These stem cells were then used to generate liver cells which mimicked a broad range of liver diseases - the first time patient-specific liver diseases have been modelled using stem cells - and to create 'healthy' liver cells from the control group. Importantly, the three diseases the scientists modelled covered a diverse range of pathological mechanisms, thereby demonstrating the potential application of their research on a wide variety of disorders."

Mitochondria are an important determinant of life span, demonstrated by some beneficial mutations and comparison between species. Researchers continue to investigate longevity mutations to better understand the underlying mechanisms: "The [known] Caenorhabditis elegans mitochondrial (Mit) mutants have disrupted mitochondrial electron transport chain (ETC) functionality, yet, surprisingly, they are long lived. We have previously proposed that Mit mutants supplement their energy needs by exploiting alternate energy production pathways normally used by wild-type animals only when exposed to hypoxic conditions. We have also proposed that longevity in the Mit mutants arises as a property of their new metabolic state. If longevity does arise as a function of metabolic state, we would expect to find a common metabolic signature among these animals. ... we show that long-lived clk-1(qm30) and isp-1(qm150) Mit mutants have a common metabolic profile that is distinct from that of aerobically cultured wild-type animals and, unexpectedly, wild-type animals cultured under severe oxygen deprivation. Moreover, we show that 2 short-lived mitochondrial ETC mutants, mev-1(kn1) and ucr-2.3(pk732), also share a common metabolic signature that is unique. ... Our study suggests long-lived, genetically specified Mit mutants employ a novel metabolism and that life span may well arise as a function of metabolic state."

A press release from InnoCentive and the SENS Foundation announces a short-term incentive program "seeking innovative ideas to biologically reverse one of the causes of aging and age-related diseases believed to be attributed to glucosepane, a protein crosslink that reduces elasticity throughout the body. This is a Theoretical Challenge, so Solvers need to submit a detailed and thorough description of their solution. The Challenge runs for 60 days and one Solver will receive $20,000 if their solution is chosen. ... Finding an innovative solution to breaking down glucosepane, or what we call 'public enemy number one,' is our Foundation's top priority in the category of protein crosslinks, as it is the most abundant protein crosslink in aged humans. We believe there are several radical possibilities to solving this Challenge - things we haven't even thought of - and will keep an open mind to solutions we receive. Our goal is to discover solutions that can be implemented and reverse stiffening, therefore restoring youthful health and vigor to the world's population. ... Evidence suggests that glucosepane may play a role in osteoporosis, cardiovascular diseases like hypertension, inflammation and diabetes. Scientists have studied the accumulation of glucosepane for 30 years with little success, so SENS Foundation is reaching out to InnoCentive's 200,000+ Solvers for innovative solutions to find a way to break the formation of glucosepane." This seems like a good way to draw attention to aspects of the SENS program that are not greatly studied - very few groups are working seriously on crosslink breakers at the present time.

From the SENS Foundation: "A comprehensive suite of rejuvenation biotechnologies must include the removal of extracellular aggregates from aging cells and tissues. The most clinically-advanced such biotechnology is immunotherapy against aggregated beta-amyloid protein (Abeta), a characteristic neuropathological lesion that accumulates in the brain in Alzheimer's disease (AD) patients and as part of "normal" brain aging. ... The promise of active and passive Abeta-targeting vaccines is high, but experimental and clinical testing of such therapies have revealed some of their limitations. Immunotherapeutics currently in clinical development rely in different ways on the mobilization of the patient's immune processes. ... Therapeutic efficacy thus depends on the patient's immune response to vaccination, which notoriously declines with aging. ... An ideal Abeta immunotherapy would thus not depend on the patient's immune system for effectiveness or safety, but would have an "intrinsic" mechanism of action ... [researchers] have made significant progress with a promising novel approach to Abeta immunotherapy that promises to deliver on all of these fronts. They have identified, purified, and characterized [antibodies] with direct hydrolytic activity against these pathological aggregates." Antibodies are the weapons used by immune cells to mark and destroy their targets - but if you can regularly infuse antibodies into the body, then you don't necessarily need the immune cells to take action.

Cancer chemotherapy is harrowing is because it is indiscriminate. But all of the old chemotherapies can be made much better and safer when used as the payload in one of the new cell targeting nanotechnologies: researchers "have developed a nano-sized vehicle with the ability to deliver chemotherapy drugs directly into cancer cells while avoiding interaction with healthy cells, increasing the efficiency of chemotherapeutic treatment while reducing its side effects. ... Inside the nano-vehicle itself are tiny particles of chemotherapy drugs. When the delivery vehicle comes into contact with cancer cells, it releases the chemotherapeutic payload directly into the cell. ... the nanomedical device can be used to treat many different types of cancer, including lung, blood, colon, breast, ovarian, pancreatic, and even several types of brain cancers. ... The key to the drug delivery platform is the molecule used to create the outer coating of this cluster nano-vehicle, a sugar recognized by receptors on many types of cancer cells. ... When the nano-vehicle interacts with the receptor on the cancerous cell, the receptor undergoes a structural change and the chemotherapy payload is released directly into the cancer cell. [This] leads to more focused chemotherapeutic treatment against the diseased cells. ... clinical trials [should] begin in two years or less."

Researchers continue to produce improvements to infrastructure technologies needed for stem cell research and development: "Human pluripotent stem cells, which can become any other kind of body cell, hold great potential to treat a wide range of ailments, including Parkinson's disease, multiple sclerosis and spinal cord injuries. However, scientists who work with such cells have had trouble growing large enough quantities to perform experiments - in particular, to be used in human studies. Furthermore, most materials now used to grow human stem cells include cells or proteins that come from mice embryos, which help stimulate stem-cell growth but would likely cause an immune reaction if injected into a human patient. To overcome those issues, MIT chemical engineers, materials scientists and biologists have devised a synthetic surface that includes no foreign animal material and allows stem cells to stay alive and continue reproducing themselves for at least three months. It's also the first synthetic material that allows single cells to form colonies of identical cells, which is necessary to identify cells with desired traits and has been difficult to achieve with existing materials."

From the Mayo Clinic: "researchers found that healthy young people who put on as little as 9 pounds of fat, specifically in the abdomen, are at risk for developing endothelial cell dysfunction. Endothelial cells line the blood vessels and control the ability of the vessels to expand and contract. ... [researchers] recruited 43 healthy Mayo Clinic volunteers with a mean age of 29 years. They were tested for endothelial dysfunction by measuring the blood flow through their arm arteries. The volunteers were assigned to either gain weight or maintain their weight for eight weeks, and their blood flow was tested. The weight-gainers then lost the weight and were tested again. ... Endothelial dysfunction has long been associated with an increased risk for coronary artery disease and cardiovascular events. Gaining a few pounds in college, on a cruise, or over the holidays is considered harmless, but it can have cardiovascular implications, especially if the weight is gained in the abdomen. ... Among those who gained weight in their abdomens (known as visceral fat), even though their blood pressure remained healthy, researchers found that the regulation of blood flow through their arm arteries was impaired due to endothelial dysfunction. Once the volunteers lost the weight, the blood flow recovered. Blood flow regulation was unchanged in the weight-maintainers and was less affected among those who gained weight evenly throughout their bodies."



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