08-08-2011 12:34 http://www.jax.org ... Bestselling author Harry Lodge, MD, wants living more years to also mean living good years. Lodge, a primary care internist who heads a 23-doctor practice in Manhattan, is co-author of Younger Next Year: Live Strong, Fit and Sexy Until You're 80 and Beyond, a book aimed at helping people make the last third of their lives the best
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Jackson Laboratory symposium: Longevity and the molecular genetics of aging - Video
ESTEEMED Frankston doctor Clive Bennetts prescribes two things for longevity: pick the right parents and don’t smoke.
The Beach St GP - who established his practice in 1962 - is celebrating 50 years of service.
And the vivacious 76-year-old said he had no plans to retire soon.
“As long as your brain is working, you keep up to date with technology and continue medical education, there’s nothing stopping you,” Dr Bennetts said.
“I promised myself three things: I must be in good health, feel wanted and enjoy my job.
“There’s no point doing it any more otherwise.”
Born in Bendigo and raised in Williamstown, Dr Bennetts spent 15 years in obstetrics, delivering more than 1000 babies.
“God has been delivering babies longer than I have; I just sit back and catch them,” he joked.
But, he said, he always knew his passion was to be a family doctor.
After graduating from Melbourne University, he began searching for the perfect location to open a practice.
Enter Frankston.
“I read an article about AV Jennings opening a sub-division in Karingal and I thought, ‘That’s where I’ll go’,” he said.
“I wanted to have a life other than medicine and Frankston was a beautiful little boutique town back in the ‘60s.
“I didn’t want them to build a shopping centre here, it has lost its charm.”
A grandfather of six, Dr Bennetts said that despite being disappointed in some of the city’s changes, he loves his town.
“We have an excellent locum service and a first-class ambulance service.
“I also think Frankston Hospital is fantastic.”
Dr Bennetts will be holding a dinner with friends, family and patients in February to celebrate.
“Doctors used to say if you take off your tie it means retirement is near.
“I took my tie off at 65 and I’m not ready to give up yet.”
Excerpt from:
Vivacity is the best medicine in Frankston
Exercise extends healthy life in laboratory animals, but not maximum life span as is the case for calorie restriction. In longer lived species such as our own, that difference may be slight: present evidence suggests exercise and calorie restriction to have broadly similar – though very different in detail – effects on life expectancy. The end results are probably in the same ballpark, and quite possibly achieved through an overlapping set of mechanisms. That said, while exercise is certainly good for you, I’ve yet to see a study on exercise that reproduces similar eye-opening changes in underlying biomarkers of health to those found in human calorie restriction practitioners. Exercise is “merely” great for health, as opposed to amazingly superb for health.
So, obviously, the sensible thing to do is both exercise regularly and practice calorie restriction. Based on the weight of evidence, this is the 80/20 of what can be done today to optimize health for the long term in a basically healthy individual. The complement to this approach is doing your part to ensure that medical technology produces methods of rejuvenation in time to help you in later age when good health practices are no longer enough to stave off significant degeneration and risk of death.
There is a school of thought that places the processes of autophagy front and center when it comes to natural methods of adjusting metabolism for length of health and life. Autophagy is the process by which cells break down damaged components, the first step in recycling and replacement: fewer damaged components at any given time is a good thing, and so more autophagy should also be a good thing. You might recall a demonstration that autophagy is essential to the life span and health benefits of calorie restriction, for example.
I notice that scientists are suggesting that autophagy is similarly important to the health and life span benefits produced by regular exercise:
Dr Levine and her team were testing a theory that exercise works its magic, at least in part, by promoting autophagy. This process, whose name is derived from the Greek for “self-eating”, is a mechanism by which surplus, worn-out or malformed proteins and other cellular components are broken up for scrap and recycled.
To carry out the test, Dr Levine turned to those stalwarts of medical research, genetically modified mice. Her first batch of rodents were tweaked so that their autophagosomes – structures that form around components which have been marked for recycling – glowed green. After these mice had spent half an hour on a treadmill, she found that the number of autophagosomes in their muscles had increased, and it went on increasing until they had been running for 80 minutes.
To find out what, if anything, this exercise-boosted autophagy was doing for mice, the team engineered a second strain that was unable to respond this way. Exercise, in other words, failed to stimulate their recycling mechanism. When this second group of modified mice were tested alongside ordinary ones, they showed less endurance and had less ability to take up sugar from their bloodstreams.
There were longer-term effects, too. In mice, as in people, regular exercise helps prevent diabetes. But when the team fed their second group of modified mice a diet designed to induce diabetes, they found that exercise gave no protection at all.
Autophagy is one of a number of potential mechanisms by which exercise improves long term health. You might look back at a post from the archives for more:
Physical inactivity is increasingly recognized as modifiable behavioral risk factor for cardiovascular diseases. A partial list of proposed mechanisms for exercise-induced cardioprotection include induction of heat shock proteins, increase in cardiac antioxidant capacity, expression of endoplasmic reticulum stress proteins, anatomical and physiological changes in the coronary arteries, changes in nitric oxide production, adaptational changes in cardiac mitochondria, increased autophagy, and improved function of sarcolemmal and/or mitochondrial ATP-sensitive potassium channels. It is currently unclear which of these protective mechanisms are essential for exercise-induced cardioprotection. … A better understanding of the molecular basis of exercise-induced cardioprotection will help to develop better therapeutic strategies.
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
Metabolism is complex – very, very complex. In areas that have been well studied for more than a decade, researchers are still pushing back and forth on whether well known genes and pathways are actually important in longevity. In this sort of environment a single study in a few dozen mice isn’t worth much, as the results from these various studies are either are all over the map, or prone to being overturned by a more careful, well-funded, and larger research project. That is what seems to have happened here for IGF-1 and longevity:
One of the major discoveries in aging during the past decade has been the observation that mutations in insulin/IGF-1 signaling led to increased longevity in various invertebrate models.
…
The most direct evidence that mutations affecting the insulin/IGF-1 signaling pathway lead to increased longevity in mammals has come from studies with Igf1r+/? mice … i.e., mice lacking one copy of the gene coding for IGF-1 receptor … In 2003, Holzenberger et al. reported that female Igf1r+/? mice exhibited a 33% increase in lifespan. … However, the lifespan data in the Holzenberger study are problematic because of the small sample size and the very short lifespan of both the wild type (WT) and Igf1r+/? mice studied.
…
therefore, we have reassessed the effect of reduced expression of the IGF-1R on lifespan using the rigorous criteria recommended by Ladiges et al., e.g., lifespan and end-of-life pathology were assessed using large sample sizes and husbandry conditions that permitted the control lifespan to approach its full potential, which are necessary if the longevity differences in the experimental group are to be relevant to healthy aging.
In agreement with Holzenberger et al., we found that the female Igf1r+/? mice were more resistant to the oxidative stress than were WT female mice while no difference was observed between the male Igf1r+/? and WT mice. However, there was only a modest increase in the mean lifespan (4.7%) of female Igf1r+/? mice compared to their WT littermates and no significant change in end-of-life pathology. Thus, our data show [that] reduced IGF-1R signaling in mammals does not play the same major role in aging that is observed in invertebrates.
And so it goes – sometimes the early results achieved in small, prospective studies with small budgets don’t hold up to closer inspection. Some fundamental processes relating to the link between operation of metabolism and longevity are very similar between lower animals (like worms) and higher animals (like mammals). You might think of the effects of calorie restriction, for example. But clearly other processes are significantly different between species, and this is one more layer of complexity that will increase the cost and slow the progress of efforts to slow aging by manipulating metabolism – such as by altering IGF-1.
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
If we could extend life decades, even centuries, what questions would have to be considered? That was the topic of Inez de Beaufort's talk at CEU, part of the 20th anniversary Center for Ethics and Law in Biomedicine lecture series.
Read the original post:
Medical ethicist Inez de Beaufort discusses life extension at CEU - Video
Ginger can be a medicine or a poison depending on when it is taken. Herbs should always be used in context.
Here is another study showing that rapamycin can extend life in mammals: “The nutrient-sensing TOR (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TOR, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of [two years]. Importantly, rapamycin was administrated intermittently (2 weeks per month) starting from the age of [two months]. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality.”
Link: http://www.ncbi.nlm.nih.gov/pubmed/22107964
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
From In Search of Enlightenment: “Looking back over our species’ history, as told in fossil records, what do we find? … Prehistoric human remains have never revealed individuals older than about 50 years of age, and humans had a life expectancy at birth of 30 years or less for more than 99.9% of the time that we have inhabited this planet. … So for most of our species’ history there was little progress in terms of increasing life expectancy at birth. But things began to change in the 19th century. Advances in technology (e.g. the sanitation revolution), medical knowledge, material resources and changes in behaviour helped change the future course of our species. … The fossil records of the 21st century will be unique in our species’ history for two reasons. Firstly, there will be more human remains this century than in any other century (because of the size of the human population). Furthermore, the vast majority of these deaths will be caused by chronic disease and will afflict people after the age of 60. Isn’t it odd, given how many people are projected to suffer and die from chronic disease and given the rapid progress that is being made in the biomedical sciences, that we don’t invest more of our energies into tackling the leading cause of chronic disease? Namely, aging. When future generations look back at the 21st century they will wonder why we didn’t act sooner to try to ameliorate the high risks of morbidity and mortality that currently ravage our bodies and minds.”
Link: http://colinfarrelly.blogspot.com/2011/12/fossil-records-past-and-present.html
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
As a follow up to an earlier post on why DNA sequencing is of interest to those of us who follow longevity science, here is a look at the present state of the sequencing industry: “BGI, based in China, is the world’s largest genomics research institute, with 167 DNA sequencers producing the equivalent of 2,000 human genomes a day. BGI churns out so much data that it often cannot transmit its results to clients or collaborators over the Internet or other communications lines because that would take weeks. Instead, it sends computer disks containing the data, via FedEx. … the ability to determine DNA sequences is starting to outrun the ability of researchers to store, transmit and especially to analyze the data. … Data handling is now the bottleneck. It costs more to analyze a genome than to sequence a genome. … That could delay the day when DNA sequencing is routinely used in medicine. In only a year or two, the cost of determining a person’s complete DNA blueprint is expected to fall below $1,000. But that long-awaited threshold excludes the cost of making sense of that data, which is becoming a bigger part of the total cost as sequencing costs themselves decline. … We believe the field of bioinformatics for genetic analysis will be one of the biggest areas of disruptive innovation in life science tools over the next few years.”
Link: http://www.nytimes.com/2011/12/01/business/dna-sequencing-caught-in-deluge-of-data.html
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
Mitochondria are the power plants of the cell, the evolved remnants of what were originally symbiotic bacteria, and which still possess their own fragile DNA distinct from that in the cell nucleus. They churn away producing the adenosine_triphosphate (ATP) used as an energy source in cellular processes, and are clearly of great importance in determining longevity. Scientists have for some years been carefully pulling apart the core mitochondrial machinery to better understand why this is the case, and here is an example of this ongoing research: “A decrease in mitochondrial electron transport chain (ETC) activity results in an extended lifespan in Caenorhabditis elegans. This longevity has only been reported when complexes I, III and IV genes are silenced, but not genes of complex II. We now have suppressed each complex II subunit in turn and have confirmed that in no case is lifespan extended. Animals with impaired complex II function exhibit similar metabolic changes to those observed following suppression of complexes I, III and IV genes, but the magnitude of the changes is smaller. Furthermore, an inverse correlation exists between mitochondrial membrane potential and ATP levels, which strongly suggests that dynamic allocation of energy resources is maintained. In contrast, suppression of genes from complexes I, III and IV, results in a metabolic crisis with an associated stress response and loss of metabolic flexibility. Thus, the maintenance of a normal metabolism at a moderately decreased level does not alter normal lifespan, whereas metabolic crisis and induction of a stress response is linked to lifespan extension.”
Link: http://www.ncbi.nlm.nih.gov/pubmed/22122855
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
The field of stem cell research is busy indeed, as is the application of new knowledge in regenerative medicine. More and more news that would have been noteworthy five years ago just slips past with a brief mention now – so you might imagine what will be buried in the academic press releases by 2016. By that time, examples of unarguably, demonstrably successful human autologous stem cell therapies will be yesterday’s news, offered to hundreds or thousands of patients in many clinics outside the US, and you’ll have to do better than repair the ravages of disease or injury in a mouse to gain the attention of the press. But for now, the following items are examples of comparatively buried news – the everyday advances in the field that are no longer written up in glowing editorials. Progress is measured by the increasing degree to which your work has faded into the background hum of science under way.
Newly discovered heart stem cells make muscle and bone:
Researchers have identified a new and relatively abundant pool of stem cells in the heart. … these heart cells have the capacity for long-term expansion and can form a variety of cell types, including muscle, bone, neural and heart cells. … While cell-based therapies do have potential for repairing damaged heart tissue, [researchers] ultimately favors the notion of regenerative therapies designed to tap into the natural ability of the heart and other organs to repair themselves. And there is more work to do to understand exactly what role these stem cells play in that repair process. [The] team is now exploring some of the factors that bring those cardiac stem cells out of their dormant state in response to injury and protect their “stemness.”
Repairing spinal cord injury with dental pulp stem cells:
Hope that a stem cell population, specifically dental pulp stem cells, might be of benefit to individuals with severe spinal cord injury has now been provided by the work of Akihito Yamamoto and colleagues, at Nagoya University Graduate School of Medicine, Japan, in a rat model of this devastating condition. In the study, when rats with severe spinal cord injury were transplanted with human dental pulp stem cells they showed marked recovery of hind limb function. Detailed analysis revealed that the human dental pulp stem cells mediated their effects in three ways: they inhibited the death of nerve cells and their support cells; they promoted the regeneration of severed nerves; and they replaced lost support cells by generating new ones.
UCLA researchers identify new method for generating stem cell-like cells from human skin:
Researchers from the UCLA School of Dentistry investigating how stem cells can be used to regenerate dental tissue have discovered a way to produce cells with stem cell-like characteristics from the most common type of human skin cell in the epidermis. These skin cells, called keratinocytes, form the outermost layer of skin and can be cultured from discarded skin tissues or biopsy specimens. … Since [these stem cells] may be obtained by taking a small punch-biopsy of skin tissues from patients, these cells are an easily accessible, patient-specific source of stem cells, which can be used for regenerative purposes.
Adult stem cells use special pathways to repair damaged muscle:
When a muscle is damaged, dormant adult stem cells called satellite cells are signaled to “wake up” and contribute to repairing the muscle. University of Missouri researchers recently found how even distant satellite cells could help with the repair, and are now learning how the stem cells travel within the tissue. This knowledge could ultimately help doctors more effectively treat muscle disorders such as muscular dystrophy, in which the muscle is easily damaged and the patient’s satellite cells have lost the ability to repair.
And that was just a random selection of stem cell news grabbed from the top of today’s pile. It’s a busy time for the life sciences, and we will all benefit from the results ten or twenty or thirty years from now.
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
Via EurekAlert!: “One of the earliest known impairments caused by Alzheimer’s disease – loss of sense of smell – can be restored by removing a plaque-forming protein in a mouse model of the disease. The study confirms that the protein, called amyloid beta, causes the loss. … The evidence indicates we can use the sense of smell to determine if someone may get Alzheimer’s disease, and use changes in sense of smell to begin treatments, instead of waiting until someone has issues learning and remembering. We can also use smell to see if therapies are working. … just a tiny amount of amyloid beta – too little to be seen on today’s brain scans – causes smell loss in mouse models. Amyloid beta plaque accumulated first in parts of the brain associated with smell, well before accumulating in areas associated with cognition and coordination. Early on, the olfactory bulb, where odor information from the nose is processed, became hyperactive. Over time, however, the level of amyloid beta increased in the olfactory bulb and the bulb became hypoactive. Despite spending more time sniffing, the mice failed to remember smells and became incapable of telling the difference between odors. The same pattern is seen in people with the disease. They become unresponsive to smells as they age. … The team then sought to reverse the effects. Mice were given a synthetic liver x-receptor agonist, a drug that clears amyloid beta from the brain. After two weeks on the drug, the mice could process smells normally. After withdrawal of the drug for one week, impairments returned.”
Link: http://www.eurekalert.org/pub_releases/2011-11/cwru-eso113011.php
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
The use of 3D printers is spreading in medical research and development: “researchers have used a 3D printer to create a bone-like material and structure that can be used in orthopedic procedures, dental work, and to deliver medicine for treating osteoporosis. Paired with actual bone, it acts as a scaffold for new bone to grow on and ultimately dissolves with no apparent ill effects. The authors [say] they’re already seeing promising results with in vivo tests on rats and rabbits. It’s possible that doctors will be able to custom order replacement bone tissue in a few years … If a doctor has a CT scan of a defect, we can convert it to a CAD file and make the scaffold according to the defect … The material grows out of a four-year interdisciplinary effort involving chemistry, materials science, biology and manufacturing. A main finding of the paper is that the addition of silicon and zinc more than doubled the strength of the main material, calcium phosphate. The researchers also spent a year optimizing a commercially available ProMetal 3D printer designed to make metal objects. The printer works by having an inkjet spray a plastic binder over a bed of powder in layers of 20 microns, about half the width of a human hair. Following a computer’s directions, it creates a channeled cylinder the size of a pencil eraser. After just a week in a medium with immature human bone cells, the scaffold was supporting a network of new bone cells.”
Link: http://medicalxpress.com/news/2011-11-3d-printer-bone-like-material.html
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
Teaching the immune system to kill cancer is an ongoing concern in laboratories around the world, and the state of the art is pretty effective these days – though in the overregulated world of medicine, a decade or more can separate working methods in the laboratory from working therapies in the clinic, and most of that delay entirely unnecessary. Here is a good example of what is presently possible:
Researchers from UCLA’s cancer and stem cell centers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma. … Researchers used a T-cell receptor from a cancer patient cloned by other scientists that seeks out an antigen expressed by this type of melanoma. They then genetically engineered the human blood stem cells by importing genes for the T-cell receptor into the stem cell nucleus using a viral vehicle. The genes integrate with the cell DNA and are permanently incorporated into the blood stem cells, theoretically enabling them to produce melanoma-fighting cells indefinitely and when needed.
…
In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, allowing Zack and his team to study the human immune system reaction to melanoma in a living organism. Over time, about six weeks, the engineered blood stem cells developed into a large population of mature, melanoma-specific T-cells that were able to target the right cancer cells. … The study included nine mice. In four animals, the antigen-expressing melanomas were completely eliminated. In the other five mice, the antigen-expressing melanomas decreased in size.
I’m not overly worried about the cancers that my body is likely to start generating in two or three decades; they will be a risk, but a small risk, more of a financial inconvenience than a genuinely threatening medical condition. By the 2040s this sort of guided approach to eliminating cancer will have long been a mainstream staple in clinics, a mature technology that will benefit from years of refinement, experience, and incremental improvements – and bear in mind that this is just one of a number of different branches of next generation cancer therapy presently under development and achieving similar results.
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
Filmed as part of the 2011 Ideas Festival, Brisbane.
View post:
Human Longevity: Is the face of survival changing? - Video
Spurring regeneration of muscle is of interest as as a part of any future rejuvenation biotechnology package because humans and other mammals progressively lose muscle mass and strength with age – aside from the sedentary lifestyle that most older people adopt, there are underlying processes that sap muscle strength even in athletes. Stepping on the gas and telling the body to build new muscle – when it ordinarily would not do so – isn’t as good an approach as preventing muscle loss from happening in the first place, or at least attenuating some of the mechanisms involved, but it certainly closer to realization at this point in time.
As a demonstration of that fact, here are researchers building new muscle in mice using one of the many specialist techniques for delivering stem cells that are presently evolving in the laboratory:
Researchers removed a portion of the tibialis anterior leg muscle in several mice (the muscle was chosen because injury to it affects the foot’s range of motion but doesn’t prevent the mice from walking). In some mice, the injuries were left to heal on their own. In others, the wound was filled with bundles of microthreads seeded with reprogrammed human muscle cells. The untreated mice developed significant scarring at the injury site, with no restoration of muscle function. In sharp contrast, the mice that received the reprogrammed cells grew new muscle fibers and developed very little scarring.
Tests done 10 weeks after implantation showed that the regenerated tibialis anterior muscle functioned with nearly as much strength as an uninjured muscle. The scientists expected that most of the regenerated muscle would be composed of human cells, since the implanted cells were from human muscle. Surprisingly, most of the new muscle fibers were made of mouse cells. The team theorized that the fibrin microthreads, which in their composition and shape are similar to muscle fibers, may encourage resident mouse progenitor cells to migrate into the wound and begin restoring the tissue (they may also forestall the natural inflammatory response that leads to scarring after a major injury).
This surprise finding suggests that fibrin microthreads alone could be used to treat major muscle trauma while research on enhancing regeneration with reprogrammed human cells continues.
Yet another line of research to keep an eye on: the ultimate destination of regenerative medicine is to move away from introducing new cells and towards using signals to tell existing cells to get to work. A lot of these potential signals are being discovered through accident and guided guesswork at the present time, but this will become a more purposeful process of discovery as understanding of the deepest and most complex levels of our biological processes increases.
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
So very much of the research we watch is conducted in mice, rats, and – increasingly – in naked mole rats and other more esoteric members of the rodent order of mammals. Some of this work is fairly directly applicable to we humans, and some of it is not. For example, the types and proportions of advanced glycation end-product (AGE) that accumulate to damage our cells in later life are very different between rodents and humans, and so early promising work in rats aimed at developing AGE-breaker drugs to wash out these unwanted compounds translated poorly to humans.
So how much attention should we give to promising results in mice? That can only be answered for any specific case by knowing more about the use of mice in the laboratory; it is very helpful for the layperson to have a better grasp as to the benefits, limitations, and expectations held by scientists when it comes to research in rodent species that is expected to be applicable to humans. On this note, let me draw your attention to a trio of long articles from Slate that examine the humble laboratory mouse:
Just how ubiquitous is the experimental rodent? In the hierarchy of lab animal species, the rat and mouse rule as queen and king. A recent report from the European Union counted up the vertebrates used for experiments in 2008 – that’s every fish, bird, reptile, amphibian, and mammal that perished in a research setting, pretty much any animal more elaborate than a worm or fly – and found that fish and birds made up 15 percent; guinea pigs, rabbits, and hamsters contributed 5 percent; and horses, monkeys, pigs, and dogs added less than 1 percent. Taken together, lab rats and lab mice accounted for nearly all the rest – four-fifths of the 12 million animals used in total,
According to one estimate, distributors like Charles River and the scientists who buy from them have created at least 400 standard, inbred strains of mouse, and 200 inbred strains of rat. Yet one stands out from the rest as the model among models in biomedicine. If you want to set up a trading post for biology, a place where researchers from around the world can exchange and compare their data, then it helps to have a common coin – a stable currency that undergirds the system. In the global marketplace of discovery, the Black-6 mouse (more formally known as the “C57BL/6″) serves as the U.S. dollar.
As a matter of taxonomy, the naked mole rat is closer to a guinea pig or porcupine than a mouse or a rat, but really it’s neither one nor the other. Buffenstein knows that she’s working with an oddball; she did a lot of the work that proves it. “[The naked mole rat] does have very unique mechanisms that are not seen in other animals,” she says, referring both to its superficial quirks and to whatever private biochemistry helps it to shrug off cancer, deflect toxic chemicals, ignore painful stimuli, and otherwise live five times longer than one might expect.
…
Ten years ago, Buffenstein was one of just a handful of biologists studying naked mole rats in captivity; now her field comprises some three dozen labs around the world. Her colleagues have looked at why naked mole rats are immune to the pain caused by spicy foods, or how they avoid getting itchy when doused with histamine, or what allows their brains to get by without much oxygen and a shriveled pineal gland. In Rochester, N.Y., a pair of Russian-born biologists, Andrei Seluanov and Vera Gorbunova, are devoted to finding out exactly how naked mole rats keep from getting cancer.
If you read around the warnings of doom by laboratory rodent monoculture – good news sells no papers, and the story of mice as research tools is one of great success when considered at the high level – you’ll find a great deal of fascinating information. It pays to understand more about how the sausage is made when it comes to longevity research, and mice are an important part of the process. Knowing more about the limitations helps to better place the steady flow of newly announced results into context.
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
FIGHT AGING! NEWSLETTER
November 21st 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!
______________________________
CONTENT
- An Unusually Clear Example of the Cost of the FDA
- The Methuselah Generation Kickstarter Project
- Longevity Mutations that Only Work With Civilization
- Some Aging Isn’t Aging
- Considering the Lab Mice
- Discussion
- Latest Headlines from Fight Aging!
AN UNUSUALLY CLEAR EXAMPLE OF THE COST OF THE FDA
The FDA holds back progress, and makes medical development either expensive or blocks it completely where the costs imposed make it impossible to profitably develop new medical technologies:
http://www.fightaging.org/archives/2011/11/an-unusually-clear-example-of-the-cost-of-the-fda.php
“The FDA, like all bureaucratic organizations, long ago came to serve its own continuance above and beyond all other goals. Its own continuance as a political organization depends on releasing as few new medical advances as possible. Approval of medicine that never causes problems gains the bureaucrats no reward, while approval of medicine that does at some point cause problems results in punishment – there is no such thing as an absolutely safe medicine, of course, and the popular media will pillory the FDA for events that are well within the expected range of risk and reward in medicine. A low rate of approval of new technologies causes little harm to the bureaucrats, in comparison, and thus is acceptable for their needs, which is to say a job and a career. Thus the self-interest of those in charge of the FDA at all levels leads to an organization structured to actively sabotage its original goals; this is more or less the place in which all government organizations wind up.
“In any case, here is an example of the cost of the FDA, with some numbers, and a line of research abandoned as being too expensive under the present regulations: Biotechnology firm Geron said last night that it would discontinue its stem-cell research program and halt a pioneering clinical study in people with spinal-cord injury. The decision brings to a halt the world’s largest and longest-running program to develop medical treatments from embryonic stem cells, versatile cells able to form many other types of human tissue. … We’re not doing this because we were souring on the field, or as a result of any problems – we have not had any safety issues at all … The attempt to study stem cells in humans had proved stupendously expensive and slow-moving for Geron. The company estimated that it spent $45 million just to win FDA approval for the initial safety trial of its treatment, known as GRNOPC1. As of October, however, only four patients had been treated, and the company would have had to spend tens of millions more in order to finish the study.”
THE METHUSELAH GENERATION KICKSTARTER PROJECT
Filmmakers are raising funds to complete their project, a film on longevity science and its future:
http://www.fightaging.org/archives/2011/11/the-methuselah-generation-kickstarter-project.php
“A while back I mentioned the Methuselah Generation, a documentary film on progress on longevity science and the future of the human life span. The more of this sort of media project underway the better, I think – the state of the science really just sells itself once you kick people into waking up and thinking about the topic of aging and rejuvenation biotechnology. The trick is to make this something that people are talking about and thinking about. In any case, the Methuselah Generation filmmakers recently drew my attention to their Kickstarter fundraising page: … Kickstarter is an all or nothing proposition: either they raise the minimum funding by the set date, $30,000 by December 26th in this case, or none of the funds are released. It’s a good system for ensuring a certain minimum level of achievement for a donor’s funds – if too little is raised to ensure a good shot at the project then your money is released to be used elsewhere.”
LONGEVITY MUTATIONS THAT ONLY WORK WITH CIVILIZATION
Why are there so many simple single gene mutations that significantly extend life and improve health in mice? Why were these not selected by evolution already?
“Deletion of the p66(Shc) gene results in lean and healthy mice, retards aging and protects from aging-associated diseases, raising the question of why p66(Shc) has been selected, and what is its physiological role. We have investigated survival and reproduction of p66(Shc) -/- mice in a population living in a large outdoor enclosure for a year, subjected to food competition and exposed to winter temperatures. Under these conditions deletion of p66(Shc) was strongly counterselected. … So in other words, lack of p66(Shc) only extends life and causes the mutants to prosper as individuals if they have the benefits of civilization and technology: secure food supplies, secure heating, protection from the elements, and so forth. If shoved out into the uncaring world, they fare poorly – and would soon enough vanish as a genetic line, out-competed by animals with shorter life spans but a better adapted metabolism. We might expect to see similar results for the range of other longevity genes discovered in small mammals: if there was an evolutionary benefit to their selection for animals in the wild, then we should expect that these longevity mutations would already have been selected.”
SOME AGING ISN’T AGING
If we think of aging as an accumulation of damage that occurs as a result of the operation of our biology, there are some grey areas:
http://www.fightaging.org/archives/2011/11/some-aging-isnt-aging.php
“We might look on aging as damage that happens as a stochastic, inevitable consequence of the operation of a biochemical system. So the buildup of chemical gunk between your cells is a part of aging, while those times you managed to break bones in your enthusiasm for life are not aging, despite the fact that what’s left in the wake of those unfortunate accidents is definitely damage. There are always special cases and grey areas worth thinking about, however. Such as teeth, for example, as I was reminded earlier today. Teeth have a pretty hard time of it, actually, when you stop to think about it. Even in this modern age our teeth maintenance technologies remain woefully inadequate in the face of bacterial species that break down enamel, and so our teeth are one of the most failure-prone and damage-prone parts of the body – and they get to the point of painful dysfunction far earlier than the rest of our organs if left to their own devices.
“But that isn’t aging – it’s parasitism, no more aging than the consequences of contracting malaria. It’s still something we need to fix, of course, and I post on this and related topics because it is of general interest to anyone who follows research into rejuvenation and regeneration. If most or all of us suffer a particular form of bacterial malfeasance that manages to be as damaging as that which chews upon our teeth, than dealing with that problem has to be included in any general toolkit for enhanced human longevity.”
CONSIDERING THE LAB MICE
An interesting trio of long articles on laboratory mice were recently published, and links can be found in the following Fight Aging! post:
http://www.fightaging.org/archives/2011/11/considering-the-mice-and-other-sundry-rodents.php
“So very much of the research we watch is conducted in mice, rats, and – increasingly – in naked mole rats and other more esoteric members of the rodent order of mammals. Some of this work is fairly directly applicable to we humans, and some of it is not. For example, the types and proportions of advanced glycation end-product (AGE) that accumulate to damage our cells in later life are very different between rodents and humans, and so early promising work in rats aimed at developing AGE-breaker drugs to wash out these unwanted compounds translated poorly to humans. So how much attention should we give to promising results in mice? That can only be answered for any specific case by knowing more about the use of mice in the laboratory; it is very helpful for the layperson to have a better grasp as to the benefits, limitations, and expectations held by scientists when it comes to research in rodent species that is expected to be applicable to humans. On this note, let me draw your attention to a trio of long articles from Slate that examine the humble laboratory mouse.”
DISCUSSION
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!
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LATEST HEADLINES FROM FIGHT AGING!
PROTEIN ACETYLATION AND AGING
Friday, November 18, 2011
http://www.fightaging.org/archives/2011/11/protein-acetylation-and-aging.php
An open access commentary: “Aging is now viewed as a plastic phenotype that can be altered by nutritional, pharmacological and genetic manipulations. However, most pro-longevity mutations are discovered by systematic gene deletion or RNA interference screens, which mainly reveal abolished or diminished gene functions. In our recent publications, we used global acetylation proteome screens to study aging in yeast, and showed that enhancing the function of certain genes through specific acetylation can promote longevity. … It is well known that acetylation of histone proteins in cultured human fibroblasts decreases during aging, which is believed to be directly related to decreased metabolic rate and reproductive capacity associated with aging. However, histone deacetylation is not likely to be a universal driving force of aging because histone acetylation and deacetylation mimetics similarly shortened life span, which could simply reflect nonspecific fitness decreases in both instances. Extension of lifespan promoted by certain genetic and/or pharmacological perturbations will more likely lead to identification of bona fide regulatory factors of aging. … Aging is conventionally thought to be characterized by accumulation of molecular, cellular, and organ damage, leading to increased vulnerability to disease and death. Our data, on the contrary, support the idea that the gradual loss of a crucial component promoting ‘healthy young status’ might underlie an intrinsic aging process. Many of the mutations that extend life span decrease the activity of external nutrient signaling, such as the IGF (insulin-like growth factor)/insulin and the TOR (target of rapamycin) pathways, suggesting that they may induce a metabolic state similar to that resulting from periods of food shortage.”
ENGINEERING THERAPEUTIC TISSUE
Friday, November 18, 2011
http://www.fightaging.org/archives/2011/11/engineering-therapeutic-tissue.php
If you can build new living tissue to be implanted in patients, then why not also give it the capacity to perform additional useful tasks? This is a technology platform with some potential: “combining gene therapy with tissue engineering could avoid the need for frequent injections of recombinant drugs. Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers [have demonstrated] the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. … Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. … The paradigm shift here is, ‘why don’t we instruct your own cells to be the factory?’ … [Researchers] provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO). … The researchers created the drug-secreting vessels by isolating endothelial colony-forming cells from human blood and inserting a gene instructing the cells to produce EPO. They then added mesenchymal stem cells, suspended the cells in a gel, and injected this mixture into the mice, just under the skin. The cells spontaneously formed networks of blood vessels, lined with the engineered endothelial cells. Within a week, the vessels hooked up with the animals’ own vessels, releasing EPO into the bloodstream. Tests showed that the drug circulated throughout the body and reversed anemia in the mice.”
ATTEMPTING A NUANCED VIEW
Thursday, November 17, 2011
http://www.fightaging.org/archives/2011/11/attempting-a-nuanced-view.php
From h+ Magazine: “As serious life extension appears on an ever nearer horizon simultaneous with a period of social and economic rebellion and an increasing sense of global chaos, this may be a good time to entertain these anxieties while thinking beyond the two extant competing simplistic arguments. The current conflicting views seem to be these: A: Hyperlongevity will be for rich people only and we can’t afford to add to the population vs. B: Technologies get distributed to more and more people at an increasing rate of speed through the auspices of the free market. Demand increases. Production increases. The price gets lower. Demand increases. Production increases. The price gets lower… ad infinitum. In fact, the wealthy who are the early adopters of a new technology get to spend a lot of money on crappy versions of new technologies that are not ready for prime time. At the risk of being obvious, it seems like there’s a lot of room in the middle for more nuanced, less certain views. … Very few people would say that we shouldn’t cure cancer or heart disease because only the wealthy will be able to afford it – and those who did would be seen by most as anti-human and/or insufferably whiny. Seen in this light, it becomes obvious that this whole ‘only the rich will get hyperlongevity’ mentality is pathetic in the extreme – a concession of defeat before the outset. If you think optimal health and longevity should be distributed, you won’t say, ‘Well, it won’t be distributed so I’m against it.’ You will try to make sure it gets distributed. Whether you believe in medical care for all through government or pushing these solutions towards a very large mass market or creating an open source culture that takes production and distribution into its own decentralized hands, you’ll work or fight for one or several (or all) of these solutions.”
THE END OF TOOTH DECAY LOOMS LARGE
Thursday, November 17, 2011
http://www.fightaging.org/archives/2011/11/the-end-of-tooth-decay-looms-large.php
Teeth are one of the first parts of our body to become seriously damaged as the years go by, thanks to bacterial agents, but that will soon enough be a thing of the past. On the one hand enamel regeneration is close to realization, and on the other hand so are ways of eliminating the agents of tooth decay: “A new mouthwash developed by a microbiologist at the UCLA School of Dentistry is highly successful in targeting the harmful Streptococcus mutans bacteria that is the principal cause tooth decay and cavities. In a recent clinical study, 12 subjects who rinsed just one time with the experimental mouthwash experienced a nearly complete elimination of the S. mutans bacteria over the entire four-day testing period. … This new mouthwash is the product of nearly a decade of research conducted by Wenyuan Shi … Shi developed a new antimicrobial technology called STAMP (specifically targeted anti-microbial peptides) [which] acts as a sort of ’smart bomb,’ eliminating only the harmful bacteria and remaining effective for an extended period. … With this new antimicrobial technology, we have the prospect of actually wiping out tooth decay in our lifetime.”
INDUCING DEDIFFERENTIATION FOR HEART REGENERATION
Wednesday, November 16, 2011
http://www.fightaging.org/archives/2011/11/inducing-dedifferentiation-for-heart-regeneration.php
As knowledge of cellular programming and signaling systems increases, the future of cell therapies will most likely move away from transplants and towards controlling existing populations of cells in the body: “In order to regenerate damaged heart muscle as caused by a heart attack [simpler] vertebrates like the salamander adopt a strategy whereby surviving healthy heart muscle cells regress into an embryonic state. This process, which is known as dedifferentiation, produces cells which contain a series of stem cell markers and re-attain their cell division activity. Thus, new cells are produced which convert, in turn, into heart muscle cells. The cardiac function is then restored through the remodelling of the muscle tissue. An optimised repair mechanism of this kind does not exist in humans. Although heart stem cells were discovered some time ago, exactly how and to what extent they play a role in cardiac repair is a matter of dispute. It has only been known for a few years that processes comparable to those found in the salamander even exist in mammals. … [Researchers have] now discovered the molecule responsible for controlling this dedifferentiation of heart muscle cells in mammals. The scientists initially noticed the high concentration of oncostatin M in tissue samples from the hearts of patients suffering from myocardial infarction. It was already known that this protein is responsible for the dedifferentiation of different cell types, among other things. … Using a mouse infarct model, the [researchers] succeeded in demonstrating that oncostatin M actually does stimulate the repair of damaged heart muscle tissue as presumed. One of the two test groups had been modified genetically in advance to ensure that the oncostatin M could not have any effect in these animals. … The difference between the two groups was astonishing. Whereas in the group in which oncostatin M could take effect almost all animals were still alive after four weeks, 40 percent of the genetically modified mice had died from the effects of the infarction.”
A TEMPORARY LIVER, AS NEEDED
Wednesday, November 16, 2011
http://www.fightaging.org/archives/2011/11/a-temporary-liver-as-needed.php
Here is an interesting application of cell therapy, which demonstrates the point that an artificial replacement for an organ doesn’t necessarily have to replicate the form and structure of that organ: “Eight-month-old Iyaad Syed now looks the picture of health – but six months ago he was close to death. A virus had damaged his liver causing it to fail. Instead of going on a waiting list for a transplant, doctors injected donor liver cells into his abdomen. These processed toxins and produced vital proteins – acting rather like a temporary liver. The cells were coated with a chemical found in algae which prevented them from being attacked by the immune system. After two weeks his own liver had begun to recover. … The question now is whether the technique could be used to benefit other patients with acute liver failure. The team [is] urging caution – a large clinical trial is needed to test the effectiveness of the technique. … The principle of this new technique is certainly ground-breaking and we would welcome the results of further clinical trials to see if it could become a standard treatment for both adults and children.”
ANOTHER INDICATOR OF THE IMPORTANCE OF AUTOPHAGY
Tuesday, November 15, 2011
http://www.fightaging.org/archives/2011/11/another-indicator-of-the-importance-of-autophagy.php
Autophagy is a collection of similar processes for cellular housekeeping: recycling broken components so that they can’t cause harm. More autophagy means a better running biological machine, and that in turn brings enhanced longevity. Aging, after all, is really nothing more than the accumulation of unrepaired biological damage. Here is another example of this principle in action: “Evidence for a regulatory role of the miR-34 family in senescence is growing. However, the exact role of miR-34 in aging in vivo remains unclear. Here, we report that a mir-34 loss-of-function mutation in Caenorhabditis elegans markedly delays the age-related physiological decline, extends lifespan, and increases resistance to heat and oxidative stress. We also found that RNAi against [autophagy-related genes] significantly reversed the lifespan-extending effect of the mir-34 mutants. Furthermore, miR-34a inhibits [gene expression of an autophagy-related gene] at the post-transcriptional level in vitro … Our results demonstrate that the C. elegans mir-34 [loss of function] mutation extends lifespan by enhancing autophagic flux in C. elegans, and that miR-34 represses autophagy by directly inhibiting the [expression of autophagy-related genes] in mammalian cells.”
STEM CELLS REVERSE HEART DAMAGE
Tuesday, November 15, 2011
http://www.fightaging.org/archives/2011/11/stem-cells-reverse-heart-damage.php
More evidence for the utility of early stage stem cell therapies of the sort that have been available overseas through medical tourism for a number of years, and which would also be available in the US if not for the FDA: “16 patients with severe heart failure received a purified batch of cardiac stem cells. Within a year, their heart function markedly improved. The heart’s pumping ability can be quantified through the “Left Ventricle Ejection Fraction,” a measure of how much blood the heart pumps with each contraction. A patient with an LVEF of less than 40% is considered to suffer severe heart failure. When the study began, Bolli’s patients had an average LVEF of 30.3%. Four months after receiving stem cells, it was 38.5%. Among seven patients who were followed for a full year, it improved to an astounding 42.5%. A control group of seven patients, given nothing but standard maintenance medications, showed no improvement at all. … We were surprised by the magnitude of improvement. … [Elsewhere] 17 patients [were] given stem cells approximately six weeks after suffering a moderate to major heart attack. All had lost enough tissue to put them ‘at big risk’ of future heart failure … The results were striking. Not only did scar tissue retreat – shrinking [between] 30% and 47% – [but] the patients actually generated new heart tissue. On average, the stem cell recipients grew the equivalent of 600 million new heart cells …. By way of perspective, a major heart attack might kill off a billion cells. … the heart contains a type of stem cell that can develop into either heart muscle or blood vessel components – in essence, whatever the heart requires at a particular point in time. The problem for patients [is] that there simply aren’t enough of these repair cells waiting around. The experimental treatments involve removing stem cells through a biopsy, and making millions of copies in a laboratory.”
PARKINSON’S RESEARCH AND MITOCHONDRIAL REPAIR
Monday, November 14, 2011
http://www.fightaging.org/archives/2011/11/parkinsons-research-and-mitochondrial-repair.php
The Parkinson’s research community may turn out to be an ally in efforts to develop mitochondrial repair technologies suitable for use in rejuvenation: “genetic mutations causing a hereditary form of Parkinson’s disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. … Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too … Normally, when mitochondria go bad, PINK1 tags Miro, [a protein which literally hitches a molecular motor onto the organelle], to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion. The organelle, unable to move, can then be disposed of: The cell literally digests it. But when either PINK1 or Parkin is mutated, this containment system fails, leaving the damaged mitochondria free to move about the cell, spewing toxic compounds and fusing to otherwise healthy mitochondria and introducing damaged components. … The study’s findings are consistent with observed changes in mitochondrial distribution, transport and dynamics in other neurodegenerative diseases … Whether it’s clearing out damaged mitochondria, or preventing mitochondrial damage, the common thread is that there’s too much damage in mitochondria in a particular brain region. … [Researchers are] interested in the possibility of helping neurons flush out bad mitochondria or make enough new, healthy mitochondria to keep them viable.”
CRYONICS MAGAZINE, 4TH QUARTER 2011
Monday, November 14, 2011
http://www.fightaging.org/archives/2011/11/cryonics-magazine-4th-quarter-2011.php
The latest Cryonics issue is out: “The 2011 4th quarter issue of Cryonics magazine is dedicated to the ‘father of cryonics,’ Robert Ettinger, who was cryopreserved on July 23, 2011. Alcor staff member Mike Perry contributes an historical piece on Ettinger and Mark Plus and Charles Platt write about his influence on contemporary cryonics, futurism, and the cryobiology community. Cryonics editor Aschwin de Wolf compiled Robert Ettinger’s mature thoughts on the feasibility of ‘mind uploading’ and situates his outlook in a broader philosophical context. This issue also features a detailed article by the Alcor Board of Directors and Management about member underfunding and its associated challenges for Alcor’s long-term financial health. Alcor member, and prolific science fiction writer, Gregory Benford is featured in this issue’s member profile.”
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http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm
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Angel Longevity Medical Center -- Los Angeles Anti-Aging - Video
If you can build new living tissue to be implanted in patients, then why not also give it the capacity to perform additional useful tasks? This is a technology platform with some potential: “combining gene therapy with tissue engineering could avoid the need for frequent injections of recombinant drugs. Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers [have demonstrated] the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. … Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. … The paradigm shift here is, ‘why don’t we instruct your own cells to be the factory?’ … [Researchers] provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO). … The researchers created the drug-secreting vessels by isolating endothelial colony-forming cells from human blood and inserting a gene instructing the cells to produce EPO. They then added mesenchymal stem cells, suspended the cells in a gel, and injected this mixture into the mice, just under the skin. The cells spontaneously formed networks of blood vessels, lined with the engineered endothelial cells. Within a week, the vessels hooked up with the animals’ own vessels, releasing EPO into the bloodstream. Tests showed that the drug circulated throughout the body and reversed anemia in the mice.”
Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm