FIGHT AGING! NEWSLETTER
July 25th 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!
- Q&A With Aubrey de Grey
- The Late Realization of Life's High Value
- There is No Such Thing as a Scientific Breakthrough
- Learning About Cryonics
- Latest Headlines from Fight Aging!
Q&A WITH AUBREY DE GREY
A recent question and answer session with Aubrey de Grey is well worth reading:
"Over at h+ Magazine you'll find a question and answer session with Aubrey de Grey that covers some old ground and some new ground. The SENS Foundation, which de Grey cofounded, is presently deploying a modest million-dollar yearly budget to work on the biotechnologies needed to repair the cellular and molecular damage that causes aging. A great deal of that budget presently goes towards the first of the Foundation's programs, an effort focused on using bacterial enzymes to break down harmful waste chemicals that build up in our cells and contribute to a range of age-related diseases and degenerations. I should mention that SENS Foundation funding is due entirely to philanthropic donations - including those of a few high net worth individuals - and I know that many of the readers here are long-standing supporters dating back to the years when the SENS Foundation's work was a program of the Methuselah Foundation. I find it very gratifying to see that so much has been made of the early efforts, when it was a matter of a few dollars given at time. I would hope that the rest of you feel the same way."
THE LATE REALIZATION OF LIFE'S HIGH VALUE
Why do people value time more greatly when they are older? Simple economics:
"When you're young, you expect to have a great deal of time ahead of you. You haven't spent much time yet, and so what remains seems like a fortune in comparison - enough to squander. Think of the way that wealthy children so often turn out despite the best efforts of their parents, their view of the value of money and economic common sense poisoned by having grown up with access to a great deal of money. But before you look down on them or pity them, think of your own situation with respect to the expected time remaining in your life. Your viewpoint on time, life, and the future was poisoned by having what appeared to be a great deal of remaining time, far more than it was easy to compare against what little you had lived to date ... so you valued time poorly. We are evolved to squander the resources that shower upon us and gather in their piles, while spending a great deal of care, thought, and worry on resources that are scarce. So we care little about air, not so very much more about water, and not at all about time when we are young. But that stock of time diminishes as you grow old, and because there is less of it, it becomes more valuable."
THERE IS NO SUCH THING AS A SCIENTIFIC BREAKTHROUGH
Science, a little like building a house, is an incremental process of largely anticipated advances that result from steady and sustained effort. If you don't see a large community of people working on a particular problem, then there's no reason to expect progress. Where there is a community working on that problem, you'll find that they have a fairly good idea as to what the next advance will be. But this is not the view that many people have of the way in which science works:
"The concept of the scientific breakthrough is firmly embedded in our popular culture: a great leap forward happens in the laboratory, ushered in by the enlightened work of a tiny inner circle of researchers, and bursts upon the world to change everything. I would argue, however, that this doesn't happen, never happens, and there is, really, no such thing as a scientific breakthrough in this sense. ... The point I want to make with all of this is that longevity science, work that will lead to biotechnologies capable of human rejuvenation, is no different. It is a process of incremental advances, requiring a large research community for any sort of reliable progress, and in which the nature of forthcoming discoveries are telegraphed by the nature of the work today.
"If you think that scientific breakthroughs are the way in which the world works, then you might be sitting there expecting significant advances in engineered human longevity to arrive no matter what the state of the present research community. Because some people are working on it, right? And it's just a few scientists and a eureka moment, right? Sadly not. One of the biggest challenges facing us today is that there is no large rejuvenation research community, and if we want to see real progress, that community must come into being - large enough and vigorous enough to match the stem cell research community pace for pace."
LEARNING ABOUT CRYONICS
If you want to learn more about the practice of cryonics, the low temperature storage of the deceased so as to preserve the fine structure of the brain for future resuscitation by advanced medical technology, then good places to start include (a) records of the history of the cryonics movement, and (b) the details of modern cryosuspension procedures:
"But how does a cryopreservation work in practice? How does one go from the last weeks of life to being safely stored in liquid nitrogen, awaiting the future? As I've noted in the past, it takes a fair amount of organization to do well, and the regulatory environment surround end of life choices doesn't make a good cryopreservation any easier - you are not allowed to choose when to do it, and in most jurisdictions no-one is allowed to help you plan your death to be at the time of your choosing either. If you want to learn more about how a cryopreservation tends to unfold, then you should note that cryonics provider Alcor publishes case summaries on a regular basis, as patients are preserved."
"The Alcor Life Extension Foundation, Inc. (Alcor) and its brother for-profit organization, Manrise Corporation (Manrise), were founded in 1972 by Fred and Linda Chamberlain ... The Chamberlains had previously been members of the Cryonics Society of California (CSC) and both had served as officers of CSC. When they became suspicious about the integrity of CSC's financial and cryogenic patient care operations and were unable to obtain answers to their questions, they left CSC and founded Alcor/Manrise. As was the model at the time, Alcor was the 501c3 non-profit organization tasked with accepting cryonics patients under the Uniform Anatomical Gift Act (UAGA) and acting as their custodian and advocate until such time as reanimation might become possible."
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!
LOCO AND FLY LONGEVITY
Friday, July 22, 2011
Here is another piece in the exceedingly complicated puzzle of metabolism and longevity, touching on some other pieces that have shown up here before, such as adenylate cyclase: "Despite the various roles of regulator of G protein signaling (RGS) protein in the G protein signaling pathway that have been defined, the function of RGS has not been characterized in longevity signaling pathways. We found that reduced expression of Loco, a Drosophila RGS protein, resulted in a longer lifespan of flies with stronger resistance to stress, higher MnSOD activity and increased fat content. In contrast, overexpression of the loco gene shortened the fly lifespan significantly, lowered stress resistance and reduced fat content, also indicating that the RGS domain containing GTPase-activating protein (GAP) activity is related to the regulation of longevity. Interestingly, expressional changes of yeast RGS2 and rat RGS14, homologs to the fly Loco, also affected oxidative stress resistance and longevity in the respective species. It is known that Loco [reduces] activity of adenylate cyclase (AC) and RGS14 interacts with activated H-Ras and Raf-1 kinases, which subsequently inhibits ERK phosphorylation. We propose that Loco/RGS14 protein may regulate stress resistance and longevity as an activator in AC-cAMP-PKA pathway and/or as a molecular scaffold that sequesters active Ras and Raf from Ras*GTP-Raf-MEK-ERK signaling pathway. Consistently, our data showed that downregulation of Loco [leads to] higher resistance to the oxidative stress."
CALORIE RESTRICTION SLOWS DNA METHYLATION IN THE HIPPOCAMPUS
Friday, July 22, 2011
DNA methylation is proposed to be a good biomarker of aging, and here researchers show that calorie restriction slows the progression of DNA methylation in the hippocampus - continuing the expected trend of calorie restriction slowing near every identified biological change that occurs with aging: "Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1-2 regions, which was prevented by CR but not by SOD1 overexpression. ... These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging."
AN EXAMPLE OF LIFESPAN EXTENSION THROUGH INDUCED HORMESIS
Thursday, July 21, 2011
Hormesis is the name given to the processes by which a little damage at the cellular level can actually be beneficial, as it spurs repair and maintenance systems to greater efforts - the result is a net gain. Here researchers demonstrate one method of inducing hormesis in nematode worms: "As organisms age, cellular proteins, lipids and nucleic acids sustain damage that can lead to functional deficits in tissues and, ultimately, death. The free radical theory of aging proposes that aging results, at least in part, from damage to cellular components by reactive oxygen species (ROS) ... Indeed, oxidative modification is a major form of damage detected in aging tissues ... Here, we report that hormetic chemicals can be modified to optimize beneficial effects and minimize toxicity in C. elegans, a model for studying aging in whole organisms. C. elegans is well-suited to this problem due to the short lifespan, ease of genetic manipulation and transparent anatomy. First, we examined whether lifespan extension is common among biological toxins with various chemical structures and mechanisms of action. In a small screen of natural phytochemicals, we identified two ROS generating compounds, plumbagin and juglone, which extended lifespan at subtoxic doses. Mean lifespan extension by plumbagin was dependent on SKN-1, a cap'n'collar transcription factor that promotes antioxidant gene expression in response to oxidative stress. We further screened a collection of six plumbagin analogs, identifying three additional naphthoquinones that activated expression of a skn-1 target. One of these could extend lifespan over a larger range of doses than plumbagin, demonstrating the utility of stress hormesis mechanisms as promising prolongevity intervention."
SNAPPING OUT OF THE PRO-DEATH TRANCE
Thursday, July 21, 2011
From TechNewsWorld: "In America, a large part of funding for regenerative medicine comes from the Department of Defense, whose goal is to repair soldiers who come home wounded. That is an effort everyone recognizes as important. Yet, when it comes to repairing older people whose hearts and lungs are failing, society seems at peace accepting their demise because that is all humanity has ever known - a state of mind that some call the 'pro-death trance.' ... A Swedish hospital recently announced that a cancer patient was saved after doctors grew him a new windpipe in the lab using a synthetic structure and the man's own stem cells. That might have sounded like science fiction just a few years ago, but today it is landmark news. Regenerative medicine has the ability to usher in radically longer and healthier lives, yet few are considering the implications. The ability to grow new replacement parts for humans when original organs break down is a game-changer when it comes to extending human 'health spans' - the amount of time one is alive and healthy. A handful of human subjects have already benefited from innovations in this area and dozens of organs have been successfully grown in the lab, including a rat heart. ... The coming changes will be enormous - but on the whole, positive. Why then, is there no sustained dialog about how to get to that point sooner? ... Humans now have the opportunity to live much longer and healthier lives - for the greater benefit of all. It is time to break free from the pro-death trance and work toward speeding the revolution."
ARGUING AGAINST A CORRELATION BETWEEN BLOOD TYPE AND AGING
Wednesday, July 20, 2011
Does blood type in any way affect longevity? A resounding "maybe" from what little work exists on the topic, which suggests that if there is any effect then it is small in comparison to other factors. But we'll never know unless the research community looks into the matter, and so here is another batch of evidence to add to the pile: "Centenarians are the best example of extreme human longevity, and they represent a selected population in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. The study of the long-lived individual genetic profile has the purpose to possibly identify the genes and the allelic variations influencing extended life expectancy, hence considering them as biomarkers of age-related diseases onset and development. The present study shows no significant differences between allelic variations of ABO blood groups among a group of centenarians from Western Sicily."
GENE THERAPY VERSUS ATHEROSCLEROSIS
Wednesday, July 20, 2011
Via EurekAlert!, news of a promising study in rabbits: "A one-dose method for delivering gene therapy into an arterial wall effectively protects the artery from developing atherosclerosis despite ongoing high blood cholesterol. ... As applied in our study, the introduced genes can produce proteins that counteract the fundamental processes that drive atherosclerosis, including preventing lipid accumulation inside the artery wall and decreasing recruitment of inflammatory cells. We found both of these effects. ... Gene transfer would move the production of the therapeutic 'drug' (in this case a therapeutic gene) directly to the site of atherosclerosis development: the blood vessel wall. The approach maximizes delivery of the drug to the artery wall and minimizes side effects in the rest of the body. ... The deployed gene produces a protein that is likely responsible for the beneficial effects of high-density lipoprotein, or HDL, commonly known as good cholesterol. This substance is apolipoprotein A-1, or apoA-1. It pumps out harmful cholesterol from the scavenger-type cells that ingest fats and congregate in early atherosclerotic lesions. ApoA-1 appears to remove cholesterol from the lesions and is capable of transporting it to the liver, where it can be excreted from the body. Lack of a suitable vector to transfer apoA-1-manufacturing genes into the cells lining the arterial wall has hampered the progress of this approach. Normally apoA-1 is produced by cells in the liver, stomach and intestine and enters the artery wall only after circulating through the blood. [The] researchers successfully used a helper-dependent adenovirus (HDAd) as the vehicle to transfer a genomic clone of rabbit apo-A1 into the carotid artery. This large blood vessel sends oxygenated blood to the brain. After the vector was infused into the artery, the gene was taken up almost exclusively by the cells in the thin layer that lines the carotid's inner surface and is in contact with circulating blood."
WHAT IS THE LIMITING FACTOR ON THE LIFESPANS OF THE OLDEST OLD?
Tuesday, July 19, 2011
Slate here ponders the consistency of the upper limits of the human lifespan: "Last month, a 114-year-old former schoolteacher from Georgia named Besse Cooper became the world's oldest living person. Her predecessor, Brazil's Maria Gomes Valentim, was 114 when she died. So was the oldest living person before her, and the one before her. In fact, eight of the last nine 'world's oldest' titleholders were 114 when they achieved the distinction. Here's the morbid part: All but two were still 114 when they passed it on. Those two? They died at 115. The celebration surrounding Cooper when she assumed the title, then, might as well have been accompanied by condolences. If historical trends hold, she will likely be dead within a year. It's no surprise that it's hard to stay the 'world's oldest' for very long. These people are, after all, really old. What's surprising is just how consistent the numbers have been." Based on the work of the Supercentenarian Research Foundation we might suspect a single class of age-limiting process - something different from the collection of common issues and biological system failures that kill most people across their 70s, 80s, and 90s. Autopsies of supercentenarians revealed that they die from a form of amyloidosis, something that you will only rarely see in younger old people. Fortunately this is very amenable to foreseeable treatments - so as rejuvenation biotechnology advances, we need not worry too greatly about this apparently limiting process.
ON INCREASING YOUR CHANCES OF AVOIDING ALZHEIMER'S
Tuesday, July 19, 2011
In many ways, Alzheimer's disease looks a lot like type 2 diabetes - it can be argued that there are some biochemical similarities in the underlying mechanisms, Alzheimer's appears to be a lifestyle disease to some degree, and the two conditions have many of the same risk factors, such as obesity and being sedentary. So: "Over half of all Alzheimer's disease cases could potentially be prevented through lifestyle changes and treatment or prevention of chronic medical conditions. ... Analyzing data from studies around the world involving hundreds of thousands of participants, [researchers] concluded that worldwide, the biggest modifiable risk factors for Alzheimer's disease are, in descending order of magnitude, low education, smoking, physical inactivity, depression, mid-life hypertension, diabetes and mid-life obesity. ... In the United States, [researchers] found that the biggest modifiable risk factors are physical inactivity, depression, smoking, mid-life hypertension, mid-life obesity, low education and diabetes. ... What's exciting is that this suggests that some very simple lifestyle changes, such as increasing physical activity and quitting smoking, could have a tremendous impact on preventing Alzheimer's and other dementias in the United States and worldwide." Many lines of research demonstrate the importance of exercise for health in later life.
FOUR SCENARIOS TO LINK PROGERIA TO AGING
Monday, July 18, 2011
In light of recent research demonstrating that the longevity-inducing drug rapamycin may treat the accelerated aging condition progeria, a researcher here offers up a fairly comprehensive commentary on what this might mean for work on "normal" aging. It is educational, but should be read with the caveat that the author has a strong conviction that the TOR gene is central in the aging process: "Here I discuss four potential scenarios, comparing progeria with both normal and accelerated aging. This reveals further indications of rapamycin both for accelerated aging in obese and for progeria. ... Scenario 1. Progerin is detectable in normal cells from normal elderly humans. In normal human fibroblasts, telomere damage during replicative senescence activates progerin production. In theory, progerin can accumulate. In this scenario, normal aging is caused by progerin or at least in some individuals accumulation of progerin is life-limiting. If so, progeria is a truly accelerated aging or at least accelerated component of aging. ... Scenario 2. Normal aging is caused by overactivation of TOR-centric pathways such as mTOR, MAPK and kinases of the DNA damage response (DDR). Progerin can activate DDR. In turn, DDR may activate the mTOR pathway. ... Therefore, by activating DDR pathways, progerin might also promote geroconversion. ... Scenario 3. mTOR inhibits autophagy and insufficient autophagy is involved in normal aging. Rapamycin also causes clearance of aggregation-prone proteins. In progeria, rapamycin activates clearance of progerin thus slowing down the progeric aging. Thus, rapamycin can affect both progeria and normal aging via activation of autophagy of different proteins and structures. ... Scenario 4. Two different mTOR activities are responsible for deceleration of normal and progeric aging. In progeria, this is autophagy. In normal aging, this is suppression of cellular hyper-functions ... Rapamycin would be effective in both conditions but by different reasons."
MARIA KONOVALENKO PRESENTS AT SINGULARITY UNIVERSITY
Monday, July 18, 2011
Longevity science advocate Maria Konovalenko recently presented at Singularity University; you'll find a link to the presentation materials in the post: "Last week I gave a talk at the Singularity University about how we can extend life. Those who have never heard about the Singularity University, should definitely check out what the SU is all about. I talked about the current records in life extension achieved in model animals, overviewed the main scientific approaches to fighting aging and looked at why activation of stress resistance genes may be a very good idea for extending our longevity. I wrapped up by noting the potential profitable business side of life extension, which is creation of geroprotective drugs. You can find the presentation "The Best Strategy for 5,000,000,000 people" here. ... A couple of pictures from the place where great ideas and poeple are mixed together with the common goal of transforming the humanity. Although, it's such a pity that life extension doen't get much attention." It is true the Singularity University crowd are less focused on radical life extension than on other transhumanist topics such as molecular manufacturing and strong AI.