FIGHT AGING! NEWSLETTER
July 11th 2011
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!
- Animating the Fable of the Dragon-Tyrant
- Noteworthy Progress in Tissue Engineering
- Naked Mole Rat Genome Sequenced
- Biomarkers of Aging: a Diagram
- Latest Headlines from Fight Aging!
ANIMATING THE FABLE OF THE DRAGON-TYRANT
A group of folk in the community had the great idea of raising a modest amount of funding to produce a web animation of the Fable of the Dragon-Tyrant, and thus broaden its audience:
"You're all, I hope, familiar with the Fable of the Dragon-Tyrant - easily the best modern fable about the scientific quest to build rejuvenation biotechnology and thereby defeat age-related frailty, suffering and death. If you have not yet read it, shame on you. Go and read it."
NOTEWORTHY PROGRESS IN TISSUE ENGINEERING
The field of tissue engineering has been in the news this past week, and rightly so:
"You might recall that one of the groups involved in recellularization research transplanted a trachea into a human recipient a couple of years ago. The organ was from a donor, stripped of all its cells, and the remaining natural scaffold of the extracellular matrix repopulated with cells from the recipient. The end result was a transplanted organ that would not be rejected by the immune system. The same researchers have now gone one step further and successfully transplanted an entirely synthetic trachea grown from the patient's cells on an artificial scaffold - no donor organ required."
"Researchers at The Saban Research Institute of Children's Hospital Los Angeles have successfully created a tissue-engineered small intestine in mice that replicates the intestinal structures of natural intestine - a necessary first step toward someday applying this regenerative medicine technique to humans."
NAKED MOLE RAT GENOME SEQUENCED
With the falling cost of DNA sequencing, it is becoming ever easier for smaller research groups and specialist interests - such as aging and longevity research - to produce larger and larger amounts of genetic data:
"Prioritizing the few exceptionally long-lived mammal species for full genome sequencing has been a few years in the making as a project, but I see that the researchers who initiated that effort have now completed the first item on their list. ... The industrious but unlovely naked mole rat is the latest creature to have its genome sequenced by scientists. A genetic blueprint for this bizarre-looking rodent could help researchers understand why it is so long-lived. ... Researchers will use the genomic information to study the mechanisms thought to protect against the causes of ageing, such as DNA repair and genes associated with these processes. To date, cancer has not been detected in the naked mole-rat. Recent studies have suggested that its cells possess anti-tumour capabilities that are not present in other rodents or in humans. Researchers at Liverpool are analysing the genomic data and making it available to researchers in health sciences, providing information that could be relevant to studies in human ageing and cancer."
BIOMARKERS OF AGING: A DIAGRAM
The Russian side of the longevity science community, largely associated with the Science for Life Extension Foundation, produce a range of very attractive documents:
"Unfortunately, many of the large posters on the fundamental science are in Russian, and only slowly make their way into English. As they usually appear online as images rather than PDFs, and are generally filled with scientific terminology, they are not particularly amenable to automated translation. But it is worth keeping an eye out for the ones that do get translated. See, for example, this recent [poster-sized example] from Alexey Moskalev."
Follow the link above to see the poster on biomarkers of aging in all its glory.
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!
AUTOLOGOUS STEM CELLS VERSUS ANGINA
Friday, July 8, 2011
Via EurekAlert!: "injections of adult patients' own CD34+ stem cells reduced reports of angina episodes and improved exercise tolerance time in patients with chronic, severe refractory angina (severe chest discomfort that did not respond to other therapeutic options). The phase II prospective, double-blind, randomized, controlled clinical trial was conducted at 26 centers in the United States ... The objective of the trial was to determine whether delivery of autologous (meaning one's own) CD34+ stem cells directly into multiple targeted sites in the heart might reduce the frequency of angina episodes in patients suffering from chronic severe refractory angina, under the hypothesis that CD34+ stem cells may be involved in the creation of new blood vessels and increase tissue perfusion. ... While we need to validate these results in phase III studies before definitive conclusions can be drawn, we believe this is an important milestone in considering whether the body's own stem cells may one day be used to treat chronic cardiovascular conditions. ... At six months after treatment, patients in the low-dose treatment group reported significantly fewer episodes of angina than patients in the control group (6.8 vs. 10.9 episodes per week), and maintained lower episodes at one year after treatment (6.3 vs. 11 episodes per week). Additionally, the low-dose treatment group was able to exercise (on a treadmill) significantly longer at six months after treatment, as compared with those in the control group (139 seconds vs. 69 seconds, on average)." If you want access to this sort of treatment now, and are resident in the US, going abroad as a medical tourist is your only realistic option. Otherwise you may still be waiting five or ten years from now: the FDA moves to approve treatments very slowly, when it moves at all.
CALORIE RESTRICTION SLOWS FERTILITY DECLINE
Friday, July 8, 2011
Another example of calorie restriction slowing a specific aspect of the damage of aging: "restricting the caloric intake of adult female mice prevents a spectrum of abnormalities, such as extra or missing copies of chromosomes, which arise more frequently in egg cells of aging female mammals. ... We found that we could completely prevent, in a mouse model, essentially every aspect of the declining egg quality typical of older females. We also identified a gene that can be manipulated to reproduce the effects of dietary caloric restriction and improve egg quality in aging animals fed a normal diet, which gives us clues that we may be able to alter this highly regulated process with compounds now being developed to mimic the effects of caloric restriction. ... The long-term effects of a caloric restriction (CR) diet in humans are being investigated in ongoing studies, but some health improvements, including reductions in cholesterol levels and other cardiovascular risk factors, have already been reported. ... While the mechanisms by which caloric restriction produces its effects are still being investigated, several of the metabolic pathways involve a regulator of DNA transcription called PGC-1a, which is known to modulate genes involved in controlling mitochondrial number and function. [The researchers] also found that egg cells from female mice lacking a functional PGC-1a gene who were allowed to free feed through adulthood maintained the same egg-cell quality as seen in the CR mice. However, combining CR with PGC-1a inactivation did not increase the effects beyond those achieved separately, which suggests that the two approaches work in a common pathway."
AGING AND THE GENETICS OF THE IMMUNE SYSTEM
Thursday, July 7, 2011
The quality of the immune system in later years has a strong impact on mortality rates and frailty - and that quality varies with different genetic profiles. Thus it follows that among the genetic variants known to affect human longevity, some are involved with the immune system: "The ageing process is very complex. Human longevity is a multifactorial trait which is determined by genetic and environmental factors. Twin and family studies imply that up to 25% of human lifespan is heritable. The longevity gene candidates have generally fallen into the following categories: inflammatory and immune-related factors, stress response elements, mediators of glucose and lipid metabolism, components of DNA repair and cellular proliferation and mitochondrial DNA haplogroups. Because of the central role of HLA molecules in the development of protective immunity and the extraordinary degree of polymorphism of HLA genes, many studies have addressed the possible impact of these genes on human longevity. Most of the data available so far demonstrated a possible role of HLA class II specificities in human longevity but definitive evidence has remained elusive. Although the data are limited and controversial, it has been hypothesized that longevity could be associated with cytokine gene polymorphisms correlating with different levels of cytokine production, thereby modulating immune responses in health and disease. Because of the essential role of cytokines in immune responses, the regulation of cytokine gene expression and their polymorphic nature, the genetic variations of these loci with functional significance could be appropriate immunogenetic candidate markers implicated in the mechanism of successful ageing and longevity."
EXPLORING IFG-1 AND LONGEVITY
Thursday, July 7, 2011
Some work here on IFG-1, not to be confused with IGF-1, which is also of interest in longevity: "When researchers at the Buck Institute dialed back activity of a specific mRNA translation factor in adult nematode worms they saw an unexpected genome-wide response that effectively increased activity in specific stress response genes that could help explain why the worms lived 40 percent longer under this condition. ... Scientists have identified a number of so-called 'longevity' genes active in many species. However, the mechanisms by which those genes impact lifespan remain poorly understood. ... the majority of research involving those genes has focused on transcription, the first level of cellular activity whereby DNA produces RNA. This research focuses on translation, whereby RNA specifies the production of proteins. ... [Researchers] inhibited expression of the mRNA translation factor, IFG-1, in adult worms. IFG-1 is important for growth and development ... "Turning down ifg-1 expression flips a switch that turned down growth and reproduction, but increased their healthspan as well as their lifespan. ... Our primary interest is to understand the biological basis of aging. This will help identify molecular targets that can be used to develop therapeutics that would slow age-related diseases and extend the healthy years of life."
SHORTER TELOMERES, HIGHER CANCER RISK
Wednesday, July 6, 2011
A confirming review of studies: "Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting. ... A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. ... The results showed that shorter telomeres were significantly associated with cancer risk compared with longer telomeres. ... Studies have showed that telomeres are critical for maintaining genomic integrity and that telomere dysfunction or shortening is an early, common genetic alteration acquired in the multistep process of malignant transformation. In addition, telomere dysfunction has been found to be associated with decreased DNA repair capacity and complex [cellular] abnormalities. Both of animal studies and clinical observations have shown that shorter telomeres were associated with increased risk of cancers, such as epithelial cancers. However, telomere shortening might play conflicting roles in cancer development. For example, the progressive loss of telomeric repeats with each cell division can induce replicative senescence and limit the proliferative potential of a cell, thus functioning as a tumor suppressor. But, once telomeres reach a critical length, it will result in chromosome break, causing genome instability and enhancing potential for malignant transformation."
MAKING BETTER CELLS FOR TISSUE ENGINEERING
Wednesday, July 6, 2011
Altering cells used in tissue engineering so as to obtain a better result is a very viable prospect, as demonstrated in a recent investigation of tendon regeneration: "The basic function of tendon is to transmit force from muscle to bone, which makes limb and joint movement possible. Therefore tendons must be capable of resisting high tensile forces with limited elongation. ... the mechanical properties of tendons are related to the fibril diameter distribution, large fibrils could withstand higher tensile forces. ... In the healing tendon, a uniform distribution of small diameter collagen fibrils has been found with poorer mechanical properties than native tissue and shows no improvement of mechanical properties with time ... The present study for the first time demonstrated the use of a scaffold-free tissue engineered tendon model for investigating the biological function of collagen V in tendon fibrillogenesis. ... Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved tendon tissue regeneration. ... These findings present a good example of in vitro tissue engineering model for tendon biology investigation and may provide basis for future development of cell or gene therapy for tendon repair."
CYCLES OF INTEREST IN CRYONICS
Tuesday, July 5, 2011
A long and interesting post at Chronosphere: "I think that most who seriously study the history of cryonics will conclude that there appear to be cycles of activism and interest. There is nothing remarkable in this: the same is true in almost any area of human undertaking. ... . What can be learned from a careful analysis of [Alcor membership from 1972 to 2010]? Is there a discernible reason why growth in membership became nearly exponential, briefly, during the early 1980s? ... there is now nearly 50 years of cryonics history. That's a substantial baseline, and if you chart the progress of cryonics over that time by almost any measure, and you look at the primary historical record, you'll immediately notice that in no way has cryonics behaved as it was predicted to do by the first generation of cryonicists (or for that matter, by any subsequent generation). ... Beyond these basic observations, if we want to understand if there are any reasons for 'bad' or 'good' intervals on these, or other indices of how cryonics has performed over time, we will necessarily have to have recourse to history. Did anything happen of historical note to jump start Alcor's growth in the 1980s? If so, what was it, and can anything be learned from examining the historical record in detail that might prove useful in assisting the growth of Alcor, and more generally the growth of cryonics, today? Do the pauses in growth and the occasional downturns that are in evidence to varying degrees in all of these charts mean anything? If so, are there lessons for us?"
MORE ON STEM CELL AGING AND ENVIRONMENTAL CUES
Tuesday, July 5, 2011
Researchers are making inroads into showing that stem cell decline with aging is a function of the surrounding environment - you might recall the experiments in which old mice were given young blood, for example. Here is another research report: "Increasing studies have demonstrated the importance of extrinsic cellular factors on the aging of adult stem cells. Aged mouse spermatogonial stem cells have been transplanted into young recipient hosts for over three years without any decline in function. Serum from old mice markedly induces embryonic stem cell dysfunction. However, the effects of the aged environment on [mesenchymal stem cell (MSC)] senescence and function have not yet been reported. In the present study, the young and the old systemic milieu were mimicked by adding 20% [young rat serum (YRS) and old rat serum (ORS)] into the culture medium respectively. The results show that the ORS culture clearly promoted senescence and [reactive oxygen species] production in the MSCs compared with those cultured with YRS. The proliferation and survival ability of the MSCs were also significantly inhibited in the ORS group compared with that in the YS group. Therefore, ORS induces MSC senescence, as well as inhibit their proliferation and survival ability."
THE SEARCH FOR WAYS TO SPUR STEM CELLS INTO ACTION
Monday, July 4, 2011
Based on work to date, it should be expected that there are effective ways to provoke existing stem cell populations in the body into greater feats of healing than normally take place. This research is an example of the type: "Injecting proteins similar to insulin directly into the heart can cause damaged cells to repair themselves and begin regenerating again, researchers said. Tests on pigs showed that the dormant cells could begin regrowth following a 'regenerative medicine' treatment using certain growth factors - naturally occurring proteins which cells use to communicate with their environment. Experts from Liverpool John Moores University (LJMU) said the four-year study presented a 'significantly different' therapy to those currently being developed by scientists. The findings, produced with teams from Italy and Spain, could lead to simple and affordable treatments for heart attacks. ... this new approach by LJMU could ultimately lead to a clinical myocardial regenerative therapy which is effective, simple, affordable, readily and widely available and easy to apply and compatible with the current clinical standard of cardiac care. ... the research shows that injecting growth factors IGF-1 and HGF caused significant 'anatomical, histological and physiological' regeneration of damaged hearts and 'sets the path' for testing clinical trials. Another member of the LJMU BioStem research team, Dr Georgina May Ellison, said funding had been secured for clinical tests of the new method to begin at the Vall d'Hebron University Hospital in Barcelona."
THE GOAL: BRING AGING UNDER MEDICAL CONTROL
Monday, July 4, 2011
Reuters reports on a recent presentation by Aubrey de Grey of the SENS Foundation: "'I'd say we have a 50/50 chance of bringing aging under what I'd call a decisive level of medical control within the next 25 years or so,' de Grey said in an interview before delivering a lecture at Britain's Royal Institution academy of science. .... And what I mean by decisive is the same sort of medical control that we have over most infectious diseases today. ... De Grey sees a time when people will go to their doctors for regular 'maintenance,' which by then will include gene therapies, stem cell therapies, immune stimulation and a range of other advanced medical techniques to keep them in good shape. ... The idea is to engage in what you might call preventative geriatrics, where you go in to periodically repair that molecular and cellular damage before it gets to the level of abundance that is pathogenic. ... For some, the prospect of living for hundreds of years is not particularly attractive, either, as it conjures up an image of generations of sick, weak old people and societies increasingly less able to cope. But de Grey says that's not what he's working for. Keeping the killer diseases of old age at bay is the primary focus. ... This is absolutely not a matter of keeping people alive in a bad state of health. This is about preventing people from getting sick as a result of old age. The particular therapies that we are working on will only deliver long life as a side effect of delivering better health."