Fight Aging! Newsletter, August 6th 2012
FIGHT AGING! NEWSLETTER
August 6th 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!
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CONTENT
- New Organ: Up to $15,000 For Social Network Engagement
- What is Aging?
- Premature Considerations of Immortality
- From a Recent Symposium on Cryonics and Dementia
- Discussion
- Latest Headlines from Fight Aging!
- The Brain is Plastic For Life
- Yet Another Theory to Explain Gender Differences in Longevity
- Engineering Viruses to Make a Better Targeted Cancer Therapy
- Tracking and Identifying Cancer Stem Cells
- Increased Resistance to Cellular Stress Common to Many Forms of Induced Longevity
- SENS Foundation Seeking Lysosomal Biology Team Lead
- Measuring Impaired Autophagy With Aging in the Pancreas
- The Point of Slowing Aging
- A Comparative Cellular and Molecular Biology of Longevity Database
- Modest Success in a Cancer Vaccine Trial
NEW ORGAN: UP TO $15,000 FOR SOCIAL NETWORK ENGAGEMENT
The New Organ 100 initiative continues to attract matching funds:
https://www.fightaging.org/archives/2012/07/new-organ-up-to-15000-for-social-network-engagement.php
"The New Organ Prize is a technology prize aimed at speeding development of tissue engineered complex organs, founded by the Methuselah Foundation. To win, a competitor must build a complex organ from a patient's own stem cells, transplant it, and have it function for two years - without making use of present stepping stone technologies such as decellularization that still require a donor organ. Start with cells and end up with patient-matched organs: that is the vision.
"One of the projects currently undertaken by the New Organ volunteers is the New Organ 100 initiative, focused on crowdsourcing the first stage of prize fundraising, raising awareness, and building support in the large community of organ donors, organ recipients, and their supporters.
"As matters proceed, the New Organ Prize continues to attract matching donations and incentives. The latest is an offer by investor Michael Matula: for every like or share on Facebook, or follower on Twitter, he will donate $1 to the prize fund - up to $15,000. In an ideal world, every reader here would think enough of the initiative to head on over and donate a modest amount, or start a fundraiser and talk a few friends into supporting the initative. If you're not up for that, however, then consider stretching your mouse fingers so far as to like the New Organ 100 page."
WHAT IS AGING?
What is aging? Like art, we know it if we see it. But once down to the detail level of evolutionary fitness, population mortality rates, and biological mechanisms, a consistent definition becomes a little challenging:
https://www.fightaging.org/archives/2012/08/what-is-aging-1.php
"In 1991, the book Evolutionary Biology of Aging offered the following definition of aging: a persistent decline in the age-specific fitness components of an organism due to internal physiological deterioration (Rose, 1991). This definition has since been used by others a number of times. However, it was only a modest generalization of a definition proffered by Alex Comfort over three editions (1956-1979) of his key book The Biology of Senescence (Comfort, 1979): "a progressive increase throughout life, or after a given stadium, in the likelihood that a given individual will die, during the next succeeding unit of time, from randomly distributed causes." ... Yet a mere definition does not necessarily tell a scientist what causally underlies the phenomenon that is so defined. The latter issue is much broader, implicitly raising fundamental scientific questions regarding mechanisms."
PREMATURE CONSIDERATIONS OF IMMORTALITY
It seems there has been a fair degree of discussion on the topic of immortality of late, more than is usual:
https://www.fightaging.org/archives/2012/08/premature-considerations-of-immortality.php
"For whatever reason, a number of public voices seem to be talking about immortality all of a sudden, largely meaning physical immortality in the sense of immunity to aging but vulnerability to fatal accidents. Topics ebb and flow like tides, I suppose, the signs of many hidden connections that underlie our culture - that grand conversation of innumerable threads held in the myriad communication channels available to us. ... Immortality can be a useful term - such as on the occasions on which you want to plant a flag a long way out in the discussion and make waves. It is, I think, becoming less useful with time, however. So many people use it without meaning or with so many varied and half-thought meanings that it is, like 'anti-aging', becoming more harmful than helpful. Too much baggage, too many charlatans of various types hitching their carts to the bandwagon.
"Putting in serious time and thought on physical immortality - $5 million here and $5 million there adds up pretty quickly - seems to me to be premature. There is a great deal of work that lies between here and first generation rejuvenation biotechnology, something that will allow us to live additional decades in good health, never mind what comes after that. The rise and rapid obsolescence of many massive industries in medicine will happen over the next fifty years in order to extend the outer limits of human health and life span far beyond the present century-and-a-bit. Each of those churning engines of progress will see millions of individuals working in hundreds of competing companies, a world of intricate detail.
"The result of all of that? Possibly humans that can live for two centuries or more before hitting as-yet unknown limits to presently envisaged biological repair technologies. This is a drop in the ocean of time. But that will give a hundred years of grace in which to work feverishly on the next generations of technology: replacements for biological systems, improving on the ways to repair and rebuild our cells, merging with our machines as those machines become ever smaller and more capable. The world of a century and a half from now will be as distant and strange and capable to us as our tools and society would seem to a 18th century peasant.
"My point is that many transformative, world-sweeping changes brought by advancing technology will occur in the decades between now and even a mere hard-fought doubling of the human life span. We'll be starting in earnest to settle the Moon and Mars by then. Our machines will be able to think for themselves. Desktop and motile nanofactories will be capable of fabricating everything from houses to gene therapies from raw materials. A sea of historical and cultural manuscripts will be written on those changes, and still fail to easily capture the scope of the way in which the world changes.
"And then it starts over again, ever building new and greater edifices as we push on to overcome the next set of limits to the human condition. All of this grand and complex near future of increasing longevity and massive change seems far more worthy of thought than immortality, given the length of the road between here and there, and how much has to be done to even start talking seriously about lives of tens of thousands of years."
FROM A RECENT SYMPOSIUM ON CRYONICS AND DEMENTIA
The folk of the Institute for Evidence Based Cryonics hosted a symposium on cryonics and dementia last month, and some of the presentation materials are available online:
https://www.fightaging.org/archives/2012/07/from-a-recent-symposium-on-cryonics-and-dementia.php
"Cryonics is the low-temperature preservation of the deceased, as rapidly as possible after death so as to preserve the fine structure of the brain before it can be damaged or decay. The body, or at least the head, are also preserved - but that is largely incidental to the real purpose, which is to store the mind encoded in the structure of neural tissue. For so long as that mind exists in low-temperature storage it has time to wait out progress in technology, the dawn of an age of medical molecular nanotechnology, and advanced tissue engineering capable of restoring that brain to live in a new body. If you have the technology to de-vitrify a brain whilst maintaining its mind, so the thinking goes, then building a body from stem cells is pretty straightforward by comparison.
"In any case, my point here is the the focus of cryonics is the brain, its structure, and the mind. Threats to the fabric of the mind are of greater importance than threats to the rest of the body in this way of looking at the world, as there exist a range medical conditions that can destroy your mind well prior to death, placing you just as far beyond help as if you burned to death, were lost at sea, or simply buried."
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!
THE BRAIN IS PLASTIC FOR LIFE
Friday, August 3, 2012
https://www.fightaging.org/archives/2012/08/the-brain-is-plastic-for-life.php
We have a great deal more control over the age-related decline of the brain than was once thought - "use it or lose it", and the ability to affect change through challenging the mind. Yet it remains the case that new biotechnology and medicine will be required to get to where we want to be, a world without the risk of dementia, fuzzy memory, and slow cognition. Still, the plasticity of the aging brain is encouraging: "There is growing evidence that, beyond what was previously believed, the adult human brain is remarkably malleable and capable of new feats - even in the last decades of life. In fact, new experiences can trigger major physical changes in the brain within just a few days, and certain conditions can accelerate this physical, chemical and functional remodeling of the brain. ... We used to think that the brain was completely formed by development and its basic structure didn't change much in adults, but as research went on we discovered that wasn't true, at least in the cerebral cortex. We now know that an underlying portion of the brain called the thalamus, which feeds the cortex information from our senses, is also remarkably plastic. ... There is no evidence that there is any part of the adult brain that is not plastic. But studies indicate that some aspects of musical training, such as the ability to perceive temporal patterns, require the brain to be trained during early developmental periods when its primed for certain types of stimuli. For other aspects of musical development, such as the ability to perceive and repeat a sequence of tones, it's irrelevant whether you've had that experience and training early in life. ... The brain is plastic for life. The fundamental thing that determines how much [persons with brain disorders] will improve is the level of their initial impairment, but not their age."
YET ANOTHER THEORY TO EXPLAIN GENDER DIFFERENCES IN LONGEVITY
Friday, August 3, 2012
https://www.fightaging.org/archives/2012/08/yet-another-theory-to-explain-gender-differences-in-longevity.php
There is no shortage of theories as to why women live longer than men - an apparently simple question, but one balanced on such a mountain of complex data and partial knowledge that it cannot be definitively answered at the present time. Here is another theory for the stack: "Mitochondria are inherited only from mothers, never from fathers, so there is no way to weed out mutations that damage a male's prospects. ... [Researchers] analysed the mitochondria of 13 different groups of male and female fruit flies. Mitochondria, which exist in almost all animal cells, convert food into the energy that powers the body. ... the results point to numerous mutations within mitochondrial DNA that affect how long males live, and the speed at which they age. ... Intriguingly, these same mutations have no effects on patterns of ageing in females. All animals possess mitochondria, and the tendency for females to outlive males is common to many different species. Our results therefore suggest that the mitochondrial mutations we have uncovered will generally cause faster male ageing across the animal kingdom. ... They suggest this is because there is no evolutionary reason for the faults that affect males to be picked up - because mitochondria are passed down by females. ... If a mitochondrial mutation occurs that harms fathers, but has no effect on mothers, this mutation will slip through the gaze of natural selection, unnoticed. Over thousands of generations, many such mutations have accumulated that harm only males, while leaving females unscathed."
ENGINEERING VIRUSES TO MAKE A BETTER TARGETED CANCER THERAPY
Thursday, August 2, 2012
https://www.fightaging.org/archives/2012/08/engineering-viruses-to-make-a-better-targeted-cancer-therapy.php
Some viruses show promise in terms of preferentially attacking cancer cells - but they can be engineered to be far more effective in the role of therapeutic agent: "Parvoviruses specifically kill cancer cells and are already in the clinical trial stage for treating malignant brain tumors. However, they can also infect normal cells - without doing any harm to them - so a large portion of viruses is lost during therapy. [Researchers] have now modified parvoviruses in such a way that they initially lose their ability to infect cells. In a second step, they equipped the viruses with a molecular key for infecting cancer cells. ... the researchers chose H1 parvoviruses, which normally infect rodents but are also infectious for human cells. H1 viruses kill tumor cells on the basis of their natural properties, i.e., their genetic material does not need to be modified for them to do so. ... The viruses exclusively destroy cancer cells. But with the same efficiency that they infect cancer cells, they also infect healthy cells. There they do not cause any damage and cannot replicate, but we lose a large portion of therapeutic viruses every time ... To solve this problem, the researchers [first] modified the genetic material of the virus in such a way that it loses its ability to infect cells. In a second step, this non-infectious virus was equipped with a molecular key for cancer cells. ... This is first evidence that it is basically possible to modify properties of H1 according to a plan. We will surely need several more attempts in order to target the viruses more specifically to cancer cells in the second step. We also already have ideas how to further enhance the infectious capacity and the potential to destroy cancer cells."
TRACKING AND IDENTIFYING CANCER STEM CELLS
Thursday, August 2, 2012
https://www.fightaging.org/archives/2012/08/tracking-and-identifying-cancer-stem-cells.php
Any commonality in present in varied types of cancer is important, as it provides a potential path to a comparatively low-cost, robust suite of therapies that work for many cancers - and a robust cancer cure is an important component of any future rejuvenation biotechnology toolkit. Here researchers add some weight to the cancer stem cell hypothesis: "Cancer researchers can sequence tumour cells' genomes, scan them for strange gene activity, profile their contents for telltale proteins and study their growth in laboratory dishes. What they have not been able to do is track errant cells doing what is more relevant to patients: forming tumours. Now three groups studying tumours in mice have done exactly that. Their results support the ideas that a small subset of cells drives tumour growth and that curing cancer may require those cells to be eliminated. It is too soon to know whether these results - obtained for tumours of the brain, the gut and the skin - will apply to other cancers, [but if they do], there is going to be a paradigm shift in the way that chemotherapy efficacy is evaluated and how therapeutics are developed. ... Underlying this scenario is the compelling but controversial hypothesis that many tumours are fuelled by 'cancer stem cells' that produce the other types of cancer cell, just as ordinary stem cells produce normal tissues. ... The papers provide clear experimental evidence that cancer stem cells exist ... They have made a major contribution to validating the concept of cancer stem cells. ... Researchers are already busy hunting for ways to kill these cells; now they have more tools to tell whether such a strategy will work."
INCREASED RESISTANCE TO CELLULAR STRESS COMMON TO MANY FORMS OF INDUCED LONGEVITY
Wednesday, August 1, 2012
https://www.fightaging.org/archives/2012/08/increased-resistance-to-cellular-stress-common-to-many-forms-of-induced-longevity.php
An open access paper, and an example of the way in which researchers are closing in on common mechanisms that explain the operation of many diverse ways found to extend healthy life in laboratory animals: "Many mutations that increase animal lifespan also confer stress tolerance, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of individual cytoprotective pathways is essential for lifespan extension, or merely correlated. To establish whether the regulatory pathways for the induction of cytoprotective responses are key in the extension of lifespan, we performed an RNAi screen for gene inactivations that decouple the activation of cytoprotective pathways from xenobiotic stimuli that normally induce them. The screen identified 29 genes that constitute the regulatory cascades of the unfolded protein response, oxidative stress response, and detoxification. ... If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction ... We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension."
SENS FOUNDATION SEEKING LYSOSOMAL BIOLOGY TEAM LEAD
Wednesday, August 1, 2012
https://www.fightaging.org/archives/2012/08/sens-foundation-seeking-lysosomal-biology-team-lead.php
A research position is open at the SENS Foundation: "SENS Foundation is hiring for our research center located in Mountain View, CA. We are seeking a team lead for our LysoSENS group to work both on established projects and new independent lysosomal-based research geared towards the SENS mission ... Qualified candidates will have a Ph.D. in the chemical/biological sciences and at least 5 years of work experience that must include prior project management experience. Duties will include bench work, management of a small team of lab researchers, the preparation of grant proposals, internal and external progress reports, individual and collaborative publication. The project lead will develop, interpret and implement standards, procedures, and protocols for the LysoSENS research program and may collaborate on determining strategic directions in the research program. Bench experience should include standard laboratory techniques, including but not limited to standard cell biology/biochemistry/molecular biology techniques. Good fundamental laboratory skills to include safety, microbial and mammalian cell culture. Experiments may include cell culture, transfection, organelle (lysosomal) purification and imaging, microscopy, protein production and analysis in addition to supervisory duties. As a project lead, candidates must have the ability to design, develop and direct experiments that establish the viability of the SENS mission and chosen therapeutic goals."
MEASURING IMPAIRED AUTOPHAGY WITH AGING IN THE PANCREAS
Tuesday, July 31, 2012
https://www.fightaging.org/archives/2012/07/measuring-impaired-autophagy-with-aging-in-the-pancreas.php
Autophagy is the important collection of processes that break down damaged cellular components and unwanted metabolic byproducts. More autophagy improves the health of the organism and extends longevity, while less autophagy leads to the reverse. Boosted autophagy appears to contribute strongly to a number of life-extending interventions, including calorie restriction, and researchers have achieved such goals as reverting aged liver function to youthful levels by increasing the effectiveness of autophagic processes. Unfortunately, autophagy declines with age as the cellular components that carry out the process become damaged and overwhelmed by metabolic waste products. Here researchers measure the impact of reduced autophagy with age in the pancreas: "Type 2 diabetes is characterized by a deficit in β-cell function and mass, and its incidence increases with age. ... Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. Autophagy may be necessary to maintain structure, mass, and function of pancreatic β-cells. In this study, we investigated the effects of age on β-cell function and autophagy in pancreatic islets of 4-month-old (young), 14-month-old (adult), and 24-month-old (old) male Wistar rats. We found that islet β-cell function decreased gradually with age. Protein expression of [autophagy markers] exhibited a marked decline in aged islets. The expression of Lamp-2, a good indicator of autophagic degradation rate, was significantly reduced in the islets of old rats, suggesting that autophagic degradation is decreased in the islets of aged rats. [Markers] of mitochondrial and nuclear DNA oxidative damage exhibited strong immunostaining in old islets. Analysis by electron microscopy demonstrated swelling and disintegration of cristae in the mitochondria of aged islets. These results suggest that β-cell and autophagic function in islets decline simultaneously with increasing age in Wistar rats, and that impaired autophagy in the islets of older rats may cause accumulation of misfolded and aggregated proteins and reduce the removal of abnormal mitochondria in β-cells, leading to reduced β-cell function. Dysfunctional autophagy in islets during the aging process may be an important mechanism leading to the development of type 2 diabetes." Reversing the decline in autophagy by restoring lysosomal function is a part of the SENS vision for rejuvenation biotechnology.
THE POINT OF SLOWING AGING
Tuesday, July 31, 2012
https://www.fightaging.org/archives/2012/07/the-point-of-slowing-aging.php
This abstract encapsulates the point made by advocates of slowing aging through metabolic manipulation by drugs or other means - that it is a far better approach than the present dominant methodologies of treating various end-stages of aging separately, and by patching over the symptoms rather than treating root causes: "Atherosclerosis, hypertension, obesity, diabetic complications, cancer, benign prostate hyperplasia, Alzheimer and Parkinson diseases, age-related macular degeneration, osteoarthritis, osteoporosis, and seborrheic keratosis are strongly associated with aging, implying a common underlying process. Each disease is treated separately and, in most cases, symptomatically. Suppression of aging itself should delay or treat all age-related diseases, thus increasing healthy life span and maximal longevity. But, is it possible to slow down aging? Recent evidence indicates that the target of rapamycin signaling pathway is involved in cellular senescence and organismal aging. Preclinical and clinical studies demonstrated the therapeutic effects of rapamycin in diverse age-related diseases. One simple reason why a single drug is indicated for so many age-related diseases is that it inhibits the aging process."
A COMPARATIVE CELLULAR AND MOLECULAR BIOLOGY OF LONGEVITY DATABASE
Monday, July 30, 2012
https://www.fightaging.org/archives/2012/07/comparative-cellular-and-molecular-biology-of-longevity-database.php
Researchers recently announced a database of interesting material on the biology of longevity - one of a growing number of publicly available online databases in this field: "Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database [as] a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP."
MODEST SUCCESS IN A CANCER VACCINE TRIAL
Monday, July 30, 2012
https://www.fightaging.org/archives/2012/07/modest-success-in-cancer-vaccine-trial.php
German researchers trialing a generally applicable cancer vaccine technology find that it improves on chemotherapy, but remains a long way from a cure. Still, this is generally how matters proceed: first results are only first results, and much improvement lies ahead. "Researchers [have] published the results of two clinical studies using the kidney-cancer vaccine IMA901 ... It is composed of ten synthetic tumor-associated peptides (TUMAPs), which activate the body's own killer T-cells against the tumor. Unlike chemotherapy, this process targets the body's immune responses and mobilizes them to attack the cancer. The studies show that this active immunization against cancer can be successful and extend the life of a patient for longer than even the latest chemotherapy techniques - with far fewer side-effects. ... All of the medications previously used have brought about a clear improvement in reducing tumor growth in cancer of the kidneys, but they did not lead to the desired extension of the patient's life and certainly did not cure the patient. ... The study shows that in kidney-cancer patients with documented T-cell reactions against two or more tumor-associated peptides, the immune reaction and clinical progress were clearly linked. That confirms the hypothesis that cancer treatments can be further developed by broadly activating the immune system against various target structures on the surface of the tumor. ... The principle applied here - of active immunization against cancer antigens previously identified in cancer cells - can be used against practically all types of cancer. ... researchers have published similarly successful clinical studies in the case of bowel cancer [and] prostate cancer. Immatics is currently carrying out studies on treatments for glioblastoma [a common and malignant brain tumor] and further studies for treating liver cancer and ovarian carcinoma are in the pipeline."
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