Longevity Meme Newsletter, November 15th 2010

November 15th 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.



- Radical Life Extension on the Radio
- The Pace of Deterioration
- The Third Dimension of Tissue Engineering
- Discussing Aging and the Immune System
- Latest Headlines from Fight Aging!


A recent Southern California Public Radio show discussed the future of human longevity:


"How old is too old? Some scientists think the body has a metabolic stop-sign at about age 122; others think that through new technologies, genetics, and robotics we can expand our longevity to a quarter millennium. And one man thinks immortality is possible - that the first human who will reach 1000 years of age has already been born. But with great age our assumptions of life, family, work, taxes, government, health, sex... our humanness...would change. Are you ready for the long life?

"You can listen to the program and leave comments at the SCPR website. I am interested to note the overwhelmingly negative nature of the comments - people pretty much lining up to declare their intent to die on schedule. I think that indicates an audience unfamiliar with the concepts of radical life extension, the great enhancement of health and life span that could be realized through rejuvenation biotechnology in the decades ahead. Presently sympathetic audiences, such as the readers of technology magazines and tech-news sites, were originally just as hostile before they began reading about longevity science more often and in greater detail.

"In the comments to this radio program, I see the bitter fruits of Malthusian environmentalism: people convinced that the world is dying, that division and development of resources is a zero-sum game, that humanity is fundamentally evil and should be removed from the world. It is an essentially religious impulse, immune to logic, immune to facts, immune to the history of Malthusian predictions proven wrong over and over again.

"So you see these strange online gatherings and discussions in which people strive to outdo one another in declaring just how eager they are to age, suffer, and die on the same schedule as their parents and their fellows. Yet when longevity science is in the clinic, they will be just as accepting of engineered longevity and longer healthy lives as they are opposed to it now - they will follow whatever the crowd follows, and it is the great shame of our age that the crowd, in its ignorance of basic economic knowledge, cries out for self-destruction, suffering, and death."


A recent study shows that the rate of decline in measurable aspects of health after 40 is a better predictor of future mortality than a snapshot of health at any point in time:


"I noticed an open access paper that explores how well the rate of change in common measures of health can predict mortality. As it turns out, quite well - better than considering snapshots in time. This makes good sense: aging is exactly the accumulation of damage and failure of systems. People who are failing faster will see their health measures change more rapidly in the crucial years between age 40 and age 60, when biochemical damage starts to seriously impact metabolism and health. ... The take away here is that actively maintained stasis is important: the longer you can keep your measurable health parameters looking like they did when you were 40, the better your chances. Making a serious go at this will of course require a sane diet and good exercise regimen at the very least - and this is likely why those people whose measurements changed to a lesser degree were better off."


Some of the truly hard challenges in medical development are not widely appreciated, and even less so once they are well on the way to being overcome:


"The difficulty of moving from the two dimensions of the petri dish cell culture to fully functioning three-dimensional tissue should not be understated: how to build the right sort of supporting scaffolding with features at the nanoscale, how to incorporate the required capillary network to supply the cells with oxygen and nutrients, how to ensure that different cell types are arranged as they would be in natural tissue, and so on. This is the sort of many-faceted problem that requires a large scientific community and a great deal of investment to solve in any reasonable amount of time - fortunately both exist in this case. Other areas of life science research and medical development should be so lucky.

"So far decellularization shows great promise, and has been used in a number of human transplant surgeries, but still requires a donor organ to supply the complex scaffolding of the extracellular matrix. Research groups have also demonstrated the ability to build a few structures that are much simpler than natural organs, but which can still perform some of the required tasks adequately - such as the tissue engineered bladders produced by Tengion."

There is a way to go yet, however, for all that the end result is in no doubt. Researchers will soon enough complete development of the means to build three-dimensional tissue reliably, rapidly, and at low cost.


The decline of the immune system into damage and misconfiguration is an important aspect of aging, as it influences so many areas of our health. Your immune system is the only barrier between you and frailty - without its function, you are weak and vulnerable, no matter how well the rest of your bodily systems are doing.


"The immune system performs many vital tasks: not just keeping out invading pathogens, but also destroying senescent cells and cancerous cells, amongst other duties. As the immune system grows weak and ineffective, disease becomes a far greater threat, cancer risk rises, and the number of senescent cells increases dramatically. ... What can be done about the failing immune system? It could - and I think should - be argued that more than enough is known to make inroads into immune system repair for the aged. This is an area with much more fuzziness in the state of knowledge than, say, mitochondrial dysfunction, but clear roads ahead still exist."

You might look back into the Fight Aging! archives for pointers to some of the possible means of immune system rejuvenation:



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, November 12, 2010
Vladimir Anisimov of the Science for Life Extension Foundation here discusses some of the differences in aging between individuals, and what might be learned from primate studies: "it is well known [that] heterogeneity is crucial feature of the aging process. There are individual peculiarities in vulnerability and resistance to stresses and stress-related pathologies among different persons due to the heterogeneity of the ageing process. It is of great importance to elucidate the individual specificity of age-related changes of the [hypothalamic-pituitary-adrenal (HPA) axis] in the context of aging of the organism as a whole and the stress-dependent age pathologies. ... [The aim of recent research] was see in which way the differences in the HPA axis function in young (6-8 years) and old (20-27 years) female rhesus monkeys depends on various behavioral types, under basal conditions, as well as under conditions of acute psycho-emotional stress. It has been found that the monkeys with depression-like behavior demonstrate age-related changes in the HPA axis function. ... taken together these results suggest that age-related dysfunctions of the HPA axis are individual features associated with peculiarities of adaptive behavior of animals. This approach seems very fruitful for future studies. Indeed, nonhuman primates and humans are [similar] in physiology of HPA: both species have cortisol as a main glucocorticoid hormone, similar circadian rhythm of HPA activity, age-related decline in DNEA sulfate secretion. Furthermore, unlike rodents, nonhuman primates feature the psycho-emotional reactions and adaptive behavior more similar to those in humans."

Friday, November 12, 2010
From Maria Konovalenko: "A recent 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. ... This study is important because it's the first to show that an artificially fabricated cornea can integrate with the human eye and stimulate regeneration. With further research, this approach could help restore sight to millions of people who are waiting for a donated human cornea for transplantation. ... Eye surgeons currently use cadaver corneas for transplants, but that requires the use of anti-rejection drugs and presents a risk of infection. Plastic corneas can also be used, but they present other problems and are generally tried only when tissue transplants have failed. To fabricate the biosynthetic cornea, human genes were inserted into yeast cells to generate recombinant human collagen. The collagen was then chemically cross-linked and molded into a scaffold in the shapes and sizes of normal human corneas. ... The implant acts like a scaffold to attract cell and nerve ingrowth, the end result is a cornea that looks and functions like a healthy cornea. ... The clinical trial consisted of 10 patients who underwent surgery on one eye to remove damaged corneal tissue and replace it with a biosynthetic cornea. Over two years of follow-up, the researchers observed that cells and nerves from the patients' own corneas had actually grown into the implant, resulting in a 'regenerated' cornea that resembled normal, healthy tissue."

Thursday, November 11, 2010
Understanding the mechanisms of regeneration implies the ability to improve it greatly: "scientists have shown that a previously overlooked group of cells - the endothelial layer of blood vessels - is essential in helping adult stem cells multiply and revitalize damaged tissue. ... In healthy adult tissues, including bone marrow, small populations of stem cells lie dormant. The trick has been to figure out what prompts them to emerge from this hibernation-like state and start proliferating to heal damaged tissue. ... The endothelium is the innermost layer of blood vessels, made up of cells that had largely been assumed to function primarily as delivery vehicles for oxygen and nutrients. But earlier this year, [researchers] figured out that these endothelial cells also release growth factors that direct bone marrow stem cells to multiply and differentiate into different types of blood cells. Now, the researchers have shown that such ability is not limited to bone marrow but exists in the endothelium of the liver, and that it can be activated to initiate and sustain liver regeneration in adult mice. [Researchers] show that by altering the activation state of the endothelium in liver and bone marrow, they could induce adult hepatocytes and blood stem cells to divide and regenerate lost tissue. ... For the last decade, physician-scientists have been trying to transplant hepatocytes to regenerate the liver. But they grow for a few months then the majority die off. Based on our data, one could argue that just transplanting hepatocytes is not going to work. To regenerate long-lasting liver, we may need to transplant hepatocytes with the properly activated endothelium, which produces the right growth factors for the hepatocytes to attach, grow, and connect with other parts of the liver."

Thursday, November 11, 2010
Researchers demonstrate an approach to tackling sarcopenia, the loss of muscle strength and mass with aging: "Skeletal muscle is dynamic, adapting to environmental needs, continuously maintained, and capable of extensive regeneration. These hallmarks diminish with age, resulting in a loss of muscle mass, reduced regenerative capacity, and decreased functionality. Although the mechanisms responsible for this decline are unclear, complex changes within the local and systemic environment that lead to a reduction in regenerative capacity of skeletal muscle stem cells, termed satellite cells, are believed to be responsible. We demonstrate that engraftment of myofiber-associated satellite cells, coupled with an induced muscle injury, markedly alters the environment of young adult host muscle, eliciting a near-lifelong enhancement in muscle mass, stem cell number, and force generation. The abrogation of age-related atrophy appears to arise from an increased regenerative capacity of the donor stem cells, which expand to occupy both myonuclei in myofibers and the satellite cell niche. Further, these cells have extensive self-renewal capabilities, as demonstrated by serial transplantation. These near-lifelong, physiological changes suggest an approach for the amelioration of muscle atrophy and diminished function that arise with aging through myofiber-associated satellite cell transplantation."

Wednesday, November 10, 2010
Deterioration in blood vessels in the brain is connected to the onset of neurodegeneration - which is an ongoing process, starting long before someone is diagnosed with dementia. It is one of the mechanisms by which brain health is connected to general health. Here, researchers shine a light on failing blood vessels in the brain: "A small amount of bleeding in the brain seems to be common among older individuals ... cerebral microbleeds are highly prevalent in the aging brain - and not primarily products of stroke-related injury, hypertension or neurodegenerative diseases such as Alzheimer's, as had been thought. ... Prior work relied on brain imaging to show cerebral microbleeds. But in this study, deep regions of the brain were closely examined under a microscope, and nearly all subjects had evidence of small areas of bleeding. ... [Researchers] studied postmortem brain specimens from 33 individuals, ranging in age from 71 to 105, with no history of stroke. Cerebral microbleeds were identified in 22 cases - all occurring in capillaries, the small blood vessels of the brain. This is a substantially higher rate of incidence than that reported in MRI studies, which have shown microbleeds in 18 percent of people between 60 and 69 and in 38 percent of those over 80. ... Results from [the] study also indicate that leakiness of brain blood vessels increases with age, [despite] the fact that a specific barrier (known as the blood-brain barrier) exists to prevent leakiness."

Wednesday, November 10, 2010
Enforced retirement by regulatory decree is a great injustice, one of the many perpetrated by government employees around the world. It must go - and retirement as an institution is clearly unsustainable in a world of increasing healthy longevity. But most people think about this issue within the box: change government regulations on retirement, don't remove regulation and let it be the choice of the individual. Sad. Here is an example from Maria Konovalenko: "schools of thought on this from biogerontologists and longevity experts including myself believe that the focus should be about making the elderly population less of a burden on the healthcare system and more productive in the workforce for longer periods of time through a global initiative on combating aging. To truly combat this crisis, a mass-scale collaborative effort similar in size to the Manhattan Project or the Apollo Project is needed so that the mechanisms that cause us to age can be identified and better understood. ... The other way to tackle this problem could be through initiating a change in retirement policies where retirement would be dependant upon biological causes as opposed to chronological age. Insurance companies could pay for appropriate medical testing to determine health status, which would be an important measure in itself. Under this scenario, individuals would be more motivated to keep their health optimized because good health would be more valuable in terms of earning potential as compared to a small monthly pension."

Tuesday, November 9, 2010
Smart Planet interviews one of the Wake Forest Institute for Regenerative Medicine researchers: "The miniature livers are a step toward achieving a transplant-able size liver. That's our goal. We need to start small in order to understand all the technical issues we will encounter as we scale up. These miniature livers can be used for drug screening. Drug screening and toxicity screening are being done on liver cells grown in the laboratory or on laboratory animals. These miniature livers will provide the closest individual system to test drugs in the laboratory. ... We have extended that functional phase [of the miniature livers] to three weeks. That's in the laboratory. We would now put these livers in rodents and see how they function. Our goal is to create a model in a rodent of a liver disease. These livers will rescue the rodents from the liver disease. ... [Because of media attention], the public starts developing hope and hype around these discoveries. It's not that we don't want people to develop hope. But with that comes caution. How long will it take us to develop the technology of getting enough cells [and] the technology of repopulating larger organs with those cells? And once we do that, how safe will these organs be for human use? Even after we confirm they pose no harm to the patient, how functional will they be and for how long? We need to consider all of that as we develop this technology for clinical use. Only once we accomplish all of these tests of toxicity, safety [and] functionality can we say we have succeeded."

Tuesday, November 9, 2010
Our cells are capable of greater feats of healing than normally take place - if they are correctly instructed to take action. One present branch of stem cell research involves discovering how to deliver those instructions: "It is well known that oral infection progressively destroys periodontal tissues and is the leading cause of tooth loss in adults. A major goal of periodontal treatment is regeneration of the tissues lost to periodontitis. Unfortunately, most current therapies cannot predictably promote repair of tooth-supporting defects. A variety of regenerative approaches have been used clinically using bone grafts and guiding tissue membranes with limited success. ... a team of researchers conducted a human clinical trial to determine the safety and effectiveness of fibroblast growth factor-2 (FGF-2) for clinical application. This is the largest study to date in the field of periodontal regenerative therapy. A randomized, double-masked, placebo-controlled clinical trial was conducted in 253 adults afflicted with periodontitis. Periodontal surgery was performed, during which one of three different doses of FGF-2 was randomly administered to localized bone defects. Each dose of FGF-2 showed significant superiority over the standard of care [for] the percentage of bone fill at 36 wks after administration, and the percentage peaked in the mid-dose FGF-2 group. These results strongly support the topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis."

Monday, November 8, 2010
Aging is biochemical and cellular damage: if you are more damaged than someone of the same chronological age, then you are physically older. This implies a shorter remaining life expectancy, but it doesn't necessarily imply that you will look older. For the purpose of close comparisons between people of a similar age, exterior appearance doesn't correlate well with the health of vital organs: "Even though most adults want to avoid looking older than their actual age, research [shows] that looking older does not necessarily point to poor health. The study found that a person needed to look at least 10 years older than their actual age before assumptions about their health could be made. ... Few people are aware that when physicians describe their patients to other physicians, they often include an assessment of whether the patient looks older than his or her actual age. This long standing medical practice assumes that people who look older than their actual age are likely to be in poor health, but our study shows this isn't always true. ... We were really surprised to find that people have to look a decade older than their actual age before it's a reliable sign that they're in poor health. It was also very interesting to discover that many people who look their age are in poor health. Doctors need to remember that even if patients look their age, we shouldn't assume that their health is fine."

Monday, November 8, 2010
From the Vancouver Sun: "Canadian scientists have transformed pinches of human skin into petri dishes of human blood - a major medical breakthrough that could yield new sources of blood for transfusions after cancer treatments or surgery ... The discovery [could] one day potentially allow anyone needing blood after multiple rounds of surgery or chemotherapy, or for blood disorders such as anemia, to have a backup supply of blood created from a tiny patch of their own skin - eliminating the risk of their body's immune system rejecting blood from a donor. Researchers predict the lab-grown blood could be ready for testing in humans within two years. ... The procedure is also relatively simple. It involves taking a small piece of skin just centimetres in size, which would require only a stitch to close, extracting fibroblasts - abundant cells in the skin that make up the connective tissue and give skin its flexibility - and bathing them in growth factors in a petri dish. Next, by adding a single protein that binds to DNA and acts as an on/off switch, the researchers turned on or off some 2,000 genes and reprogrammed the skin cells to differentiate or morph into millions of blood progenitors - the cells the produce blood."



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