Fight Aging! Newsletter, June 11th 2012

June 11th 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!



- Growing a Small Mass of Liver Tissue From Stem Cells
- Heart Rate Variability in Calorie Restriction Practitioners
- An Introduction to Microglia in the Aging Brain
- Discussion
- Latest Headlines from Fight Aging!


The press are noting that a Japanese group has managed to grow a small mass of functional liver tissue from stem cells:

"The liver is likely to be one of the earliest human organs grown to order from a patient's stem cells: liver tissue is already far more capable of regeneration than the tissues of other organs, and researchers have been making good progress in recent years in coaxing stem cells to form live tissue. As of today, a press report is doing the rounds to claim that a Japanese group have managed to grow a small functional mass of liver tissue - calling it a liver is no doubt considerably overstating the case, given the small size. Details are somewhat light on the ground, but we'll no doubt hear more soon.

"Japanese researchers have created a functioning human liver from stem cells, a report says. ... A team of scientists transplanted induced pluripotent stem (iPS) cells into the body of a mouse, where it grew into a small, but working, human liver, the Yomiuri Shimbun said. A team led by professor Hideki Taniguchi at Yokohama City University developed human iPS cells into 'precursor cells', which they then transplanted into a mouse's head to take advantage of increased blood flow. The cells grew into a human liver 5 millimetres (0.2 inches) in size that was capable of generating human proteins and breaking down drugs, the Yomiuri reported. An abstract of Taniguchi's research was delivered to regenerative medicine researchers ahead of an academic conference next week, but Taniguchi declined to comment to AFP before the meeting."


I recently pointed out research on the younger hearts possessed by long-term practitioners of calorie restriction, and here is more on that topic:

"People who practice calorie restriction over the long term have physiologically younger cardiovascular systems - meaning notably less low-level cellular damage and better function than their peers of a similar chronological age. ... If there was a drug that did that, its financials would be staggering - and you'd never hear the end of it. It would be publicized and popularized in every corner of the world. But just ask someone to exercise a little willpower and planning in their diet to gain the same results ... and therein lies a lesson with regard to human nature.

"The idea was to learn, first of all, whether humans on CR, like the calorie-restricted animals that have been studied, have a similar adaptation in heart rate variability. The answer is yes. We also looked at normal levels of heart rate variability among people at different ages, and we found that those who practice CR have hearts that look and function like they are years younger ... This is really striking because in studying changes in heart rate variability, we are looking at a measurement that tells us a lot about the way the autonomic nervous system affects the heart. And that system is involved not only in heart function, but in digestion, breathing rate and many other involuntary actions. We would hypothesize that better heart rate variability may be a sign that all these other functions are working better, too. ... Higher heart rate variability means the heart can adjust to changing needs more readily. Heart rate variability declines with age as our cardiovascular systems become less flexible, and poor heart rate variability is associated with a higher risk of cardiovascular death."


The immune system is important in aging, and arguably more so in the brain than elsewhere - since we can't just write off and replace the brain wholesale using the regenerative medicine of tomorrow, as we can for other organs.

"Microglia are immune cells that defend and clean up the brain and spinal cord. Like the rest of the immune system, they progressively fail in their work with age. Worse, like other immune system components, they begin to become actively harmful by causing chronic inflammation and other forms of damage instead of helping. Reversing that trend is one important line of research among many that, as they produce working medical technologies, will extend our healthy life spans. ... So microglia, as an important part of the existing maintenance systems in the brain, are of considerable interest. Can early successes be obtained by boosting their activity, or slowing or reversing their decline with age?"


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, June 8, 2012
Andrew Weil, who is something of an apologist for aging, here holds forth on the merits of intermittent fasting (IF) - shown to improve health and extend life in laboratory animals through mechanisms that largely, but not entirely, overlap with those of calorie restriction: "An IF regime works, proponents say, because it aligns with our evolutionary history. Over the 250,000 years that Homo sapiens have been around, food supply has waxed and waned. We evolved to take advantage of this fact, building muscle and fatty tissue during times of abundance, then paring it back during lean ones. Fasting periods accelerate the clearing-out of waste left by dead and damaged cells, a process known as autophagy. A failure of autophagy to keep up with accumulated cellular debris is believed by many scientists to be one of the major causes of the chronic diseases associated with aging. Occasional fasting also seems to boost activity and growth of certain types of cells, especially neurons. This may seem odd, but consider it from an evolutionary perspective - when food is scarce, natural selection would favor those whose memories ("Where have we found food before?") and cognition ("How can we get it again?") became sharper. Research indicates that the benefits of IF may be similar to those of caloric restriction (CR) in which there are regular meals, but portions are smaller than normal. ... The positive effects of IF have been chronicled in a variety of animal and human studies, starting with a seminal experiment in 1946, when University of Chicago researchers discovered that denying food every third day boosted rats' lifespans by 20 percent in males, 15 percent in females. A 2007 review by University of California, Berkeley, researchers concluded that alternate-day fasting may: 1) Decrease cardiovascular disease risk. 2) Decrease cancer risk. 3) Lower diabetes risk (at least in animals, data on humans were less clear, possibly because the trial periods in the studies were not long enough to show an effect). 4) Improve cognitive function. 5) Protect against some effects of Alzheimer's and Parkinson's diseases."

Friday, June 8, 2012
This interview, machine-translated from the Russian, will be of interest to those who look into the history of transhumanist thought on the defeat of aging and radical life extension. It has deep roots back into the early 20th century, and one thread of these ideas was evolving through the ongoing disaster that was Russia of that century - the Russian cosmists are thought of as important predecessors to modern transhumanism, for example. These are some thoughts and recollections of someone who was publishing and thinking on the topic in the 1960s and later; note that the Russian end of the longevity science community are far from shy when it comes to talking about physical immortality as the end goal of medicine: "Meanwhile, today, in the [21st] century, when we talk about the necessity of victory over death, of making real the possibility of personal immortality and resurrection [of cryopreserved] people - people often do not even bother to think about it, but with some, or even masochistic pleasure begin to look for rebuttal. One would think, what to look for them? Why create additional obstacles? Chance of dying there at all. So there is nothing to lose. Is not it better to try to work together and find ways to avoid it? ... But, oddly enough, and sadly, no modern humanity, nor any single country (maybe with the exception of Japan, as far as I know), even such a purpose not intended. It's still pretty amazing! After all, people continue to die today, but no action is [taken]. How so? ... And yet ... There is no doubt the science over the past half century has leaped forward. Scientific and technological progress has radically changed many things in our lives. And the inspirational process is irreversible. You ask ... where the source of my optimism. He is in me and outside me. This is my inner conviction, supported by all the progressive tradition of Russian philosophical thought and [unstoppable] scientific thought."

Thursday, June 7, 2012
Via EurekAlert!: "For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease. ... It is generally accepted that the buildup of artery-blocking plaque stems from the body's immune response to vessel damage caused by low-density lipoproteins ... Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue ... The scar tissue, known as neointima, has certain characteristics of smooth muscle, the dominant type of tissue in the blood vessel wall. Because mature smooth muscle cells no longer multiply and grow, it was theorized that in the course of the inflammatory response, they revert, or de-differentiate, into an earlier state where they can proliferate ... However, no experiments published have directly demonstrated this de-differentiation process ... researchers turned to transgenic mice with a gene that caused their mature smooth muscle cells to glow green under a microscope. In analyzing the cells from cross sections of the blood vessels, they found that more than 90 percent of the cells in the blood vessels were mature smooth muscle cells. They then isolated and cultured the cells taken from the middle layer of the mouse blood vessels. ... Notably, none of the new, proliferating cells glowed green, which meant that their lineage could not be traced back to the mature smooth muscle cells originally isolated from the blood vessels. ... We did further tests and detected proteins and transcriptional factors that are only found in stem cells. No one knew that these cells existed in the blood vessel walls because no one looked for them before. ... In the later stages of vascular disease, the soft vessels become hardened and more brittle. Previously, there was controversy about how soft tissue would become hard. The ability of stem cells to form bone or cartilage could explain this calcification of the blood vessels. ... Other tests in the study showed that the multipotent stem cells were dormant under normal physiological conditions. When the blood vessel walls were damaged, the stem cells rather than the mature smooth muscle cells became activated and started to multiply." Though if you want to consider root causes, look at mechanisms like accumulated damage to mitochondria that leads to a greater level of oxidized low-density lipoproteins in the blood.

Thursday, June 7, 2012
One of the costs of being sedentary is fiscal: the cost of medical services you would otherwise not have needed due to your increased risk of age-related disease. Here is another researcher running the numbers: "Physical inactivity is a recognized public health issue in Canada and globally ... A common approach for assessing the public health impact of physical inactivity is to measure the prevalence of the population not meeting physical activity guidelines. Recent surveillance data based on objective measures indicate that 85% of Canadian adults do not meet Canada's physical activity guidelines of 150 min/week of moderate-to-vigorous physical activity ... A second approach for assessing the public health impact of physical inactivity is to estimate the proportion of a disease within the population that is directly attributable to physical inactivity. For instance, 19% of the coronary artery disease cases in Canadian men are due to physical inactivity ... A third approach for assessing the public health impact of physical inactivity is to estimate the financial burden it places on the health care system and economy. The most recent Canadian estimates, based on 2001 data, suggest that the annual economic burden of physical inactivity is $5.3 billion. ... Similar to the 2001 estimates, the health care cost of physical inactivity in this report was estimated using a prevalence-based approach, which required 3 pieces of information: (1) the risks of chronic conditions in physically inactive individuals, (2) the direct and indirect costs of these chronic diseases, and (3) the prevalence of physical inactivity in the population. ... The estimated direct, indirect, and total health care costs of physical inactivity in Canada in 2009 were $2.4 billion, $4.3 billion, and $6.8 billion, respectively. These values represented 3.8%, 3.6%, and 3.7% of the overall health care costs." It is interesting to compare these numbers with research on individual lifetime medical cost differences that stem from being out of shape, and with some other number crunching on the economics of health and longevity.

Wednesday, June 6, 2012
Here is a study that points to amount of visceral fat as a dominant contribution to the risk of age-related type-2 diabetes - a condition rarely suffered by people who successfully avoid putting on weight over the years - something that doesn't just happen, but requires exercise and a sensible approach to diet and lifestyle. "A collaborative re-analysis of data from the InterAct case-control study [has] established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index (BMI). Reporting in this week's PLoS Medicine, the researchers estimated the association of BMI and waist circumference with type 2 diabetes from measurements of weight, height and waist circumference, finding that both BMI and waist circumference were independently associated with type 2 diabetes risk but waist circumference was a stronger risk factor in women than in men. ... The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident [type 2 diabetes] cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. ... These findings indicate that targeted measurement of waist circumference in overweight individuals (who now account for a third of the US and UK adult population) could be an effective strategy for the prevention of diabetes because it would allow the identification of a high-risk subgroup of people who might benefit from individualised lifestyle advice. ... Our results clearly show the value that measurement of [waist circumference] may have in identifying which people among the large population of overweight individuals are at highest risk of diabetes." A risk that is essentially yours to create, remove, or manage through the choices you make.

Wednesday, June 6, 2012
The SENS Foundation Academic Initiative continues to grow, laying the foundation for the next generation of researchers working on rejuvenation biotechnology: "The Academic Initiative is likely to see another increased budget in 2013. We plan to offer at least as many scholarships and grants as we're offering this year, while we are nearly certain to expand our summer internship program, bringing in more interns overall and sending them to a greater number of labs. This year, some interns have been placed at the SENS Foundation Research Center, while others have gone to the Buck Institute for Research on Aging. We hope to place more interns at each location next year, and to add new locations. The Initiative's budget may not be the only thing that changes with the coming of the new year. SENS Foundation itself is still planning a revamp of its website, and the Academic Initiative won't miss that chance to have its own website enhanced further. Planning for our own next website has begun: long story short, it'll be simpler with less text and will offer very clear and immediate ways for students to get started. Some graphic design work that will go online with that new site is also underway. We'd like to finish by pointing out that we still have enough funding to continue to award materials grants throughout the summer and into the Fall 2012 semester. Since many students have extra time to put a proposal together over the summer, and since we're currently seeing a (likely summer-related) increase in interest in our grants, this is a particularly good time to apply."

Tuesday, June 5, 2012
Researchers dig deeper into the mechanisms of breast cancer risk: "Age-related physiological changes, including endocrine profiles and alterations of the microenvironments surrounding breast cells, have been associated with increased cancer risks, but the underlying cellular mechanisms behind these changes and their links to cancer have not been explained. ... Studying the aging process in any human tissue is a challenge primarily because of limited access to samples ... Human mammary epithelial cells (HMECs) are one of the few examples of an epithelial tissue that affords relatively good access because of mastectomies and cosmetic reduction surgeries. In both cases, surgical discards provide sample tissue for research [and researchers] were able to generate a large collection of normal HMEC strains derived from primary tissue in women aged 16 to 91 years. ... [The result was] a study in which it was determined that aging causes an increase in multipotent progenitors - a type of adult stem cell believed to be at the root of many breast cancers - and a decrease in the myoepithelial cells that line the breast's milk-producing luminal cells and are believed to serve as tumor suppressors. ... [Researchers] discovered that in finite-lifespan cultured and uncultured epithelial cells, the advancing years usher in a reduction of myoepithelial cells and an increase in luminal cells that express the proteins keratin 14 and integrin α6. In women under 30, these proteins are expressed almost exclusively in myoepithelial cells. ... The aging process therefore results in both a shift in the balance of luminal/myoepithelial lineages and to changes in the functional spectrum of multipotent progenitors that together appear to increase the potential for malignant transformation. We corroborated our culture data with parallel analyses of in vivo samples, but we still have dots to connect to demonstrate that these changes relate to an increased risk of malignancy. All the signs are there, though."

Tuesday, June 5, 2012
Via EurekAlert!: "When autologous (self-donated) lung-derived mensenchymal stem cells (LMSCs) were transplanted endoscopically into 13 adult female sheep modeled with emphysema, post-transplant evaluation showed evidence of tissue regeneration with increased blood perfusion and extra cellular matrix content. Researchers concluded that their approach could represent a practical alternative to conventional stem cell-based therapy for treating emphysema. ... previous transplantation studies, many of which used an intravenous delivery method, have shown that [bone marrow derived mensenchymal stem cells (BM-MSCs)] have been only marginally successful in treating lung diseases. Further, therapeutic responses in those studies have been limited to animal models of inflammatory lung diseases, such as asthma and acute lung injury. To try and answer the questions surrounding the utility of BM-MSCs for treating advanced emphysema, a disease characterized by tissue destruction and loss of lung structural integrity, for this study the researchers isolated highly proliferative, mensenchymal cells from adult lung parenchyma (functional tissue) (LMSCs) and used an endoscopic delivery system coupled with a scaffold comprised of natural extracellular matrix components. ... despite the use of autologous cells, only a fraction of the LMSCs delivered to the lungs alveolar compartment appeared to engraft. Cell death likely occurred because of the failure of LMSCs to home to and bind within their niche, perhaps because the niche was modified by inflammation or fibrosis. These cells are attachment-dependent and failure to attach results in cell death. Their findings did suggest, however, that LMSCs were capable of contributing to lung remodeling leading to documented functional improvement rather than scarring 28 days post transplantation."

Monday, June 4, 2012
Researchers became interested in the Pink1 gene and its protein product because mutations in it are associated with a form of Parkinson's disease. Pink1 appears to be important in mitochondrial quality control: it is a part of the machinery that ensures damaged mitochondria can be effectively destroyed. Regular readers will know that an accumulation of damaged mitochondria is an important contribution to aging, so it should is perhaps not surprising that boosting levels of Pink1 extends life, here demonstrated in flies: "Overexpression of the gene coding for α-synuclein has been shown to be an inherited cause of Parkinson disease. Our laboratory has previously co-expressed the parkin and Pink1 genes to rescue α-synuclein-induced phenotypes within a Drosophila model. To further investigate the effect of Pink1 in this model, we performed longevity and behavioral studies using several drivers to express the α-synuclein and Pink1 genes. Our findings showed that overexpression of Pink1 and overexpression of Pink1 with α-synuclein resulted in an increased lifespan when driven with the TH-Gal4 transgene. This increase in longevity was accompanied by an increased healthspan, as measured by mobility over time, suggesting that this is an example of improved functional aging. Our results indicate that, in the dopaminergic cells targeted by TH-Gal4, increased expression of α-synuclein and Pink1 together have a synergistic effect, allowing for enhanced protection and increased survival of the organism."

Monday, June 4, 2012
Over at the IEET blog, a video interview: "Sonia Arrison is the author of "100 Plus: How the Coming Age of Longevity Will Change Everything, from Careers and Relationships to Family and Faith." In this video, Sonia discusses: how and why she got interested in technology in general and transhumanism and regenerative medicine in particular; how science and technology will allow us to live longer and healthier lives; the most common objections against increased longevity; the implications thereof on major religions; cryonics; her take on the technological singularity and our chances of surviving it; the fact that we cannot simply sit down and wait for longevity to happen." As noted, the future isn't a conveyor belt automatically bringing us better medicine and extended healthy life: every advance has to be advocated, funded, and built by someone. If too few people are working on longevity science, then rejuvenation biotechnology will not be developed in time.



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