Longevity Meme Newsletter, April 19 2010

April 19 2010

The Longevity Meme 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 the Longevity Meme.



- Delivering New Enzymes to Clean Up Old Cells
- Humanity+ UK 2010 Conference, April 24th
- Deathism From an Expected Quarter
- Reports From the Bay Area Aging Club
- Discussion
- Latest Healthy Life Extension Headlines


Our metabolisms generate a small but steadily growing amount of waste chemicals that cannot be broken down in the body. This junk accumulates in the recycling mechanism called the lysosome, and is especially problematic in long-lived cell populations, such as those that exist in the nervous system and brain. Recycling breaks down and the cells malfunction, causing more damage elsewhere, or die. What can we do about this?


"Medical bioremediation is the name given to the SENS Foundation approach to removing one class of harmful waste chemicals that accumulate in our cells with advancing age. The development of therapies of biomedical remediation breaks down into two distinct lines of research: firstly, to identify naturally occurring bacterial enzymes that digest these unwanted junk chemicals. We know that bacteria containing these enzymes exist because we find no remnants of this chemical junk in graveyards, battlefields, slaughterhouse grounds, and so forth. The SENS Foundation funds a program aimed at discovering enzymes that will be safe to introduce into the human body, and have achieved some degree of success in recent years.

"The second theme in biomedical remediation research is the delivery of suitable enzymes to where they are needed: the lysosomes within our cells. Fortunately, this is an area in which many researchers are already hard at work. There exists a category of genetic disorders, the lysosomal storage diseases, in which the lysosome is dysfunctional or lacks one or more vital enzymes. Advances in repairing these conditions by delivering the correct enzymes to a patient's lysosomes are also applicable to biomedical remediation aimed at rejuvenating the malfunctioning, clogged-up lysosomes of the elderly."


British transhumanists are holding a conference in London later this month. Amongst those speaking is biomedical gerontologist Aubrey de Grey, so take the time to drop by if you're in the area.


"The UK chapter of Humanity+, an organisation dedicated to promoting understanding, interest and participation in fields of emerging innovation that can radically benefit the human condition, announced today that registrations are on track for record attendance at the Humanity+ UK2010 conference taking place in Conway Hall, Holborn, London, on April 24th.

"Transhumanism is simple common sense as applied to thinking about technology, the human condition, and the future. We look back to see that life was harder in the past: people were less wealthy and less capable, living lives made narrow by comparative lack of choice and tool-aided ability. Today we are not just better off, but actually better than our ancestors: healthier, more broadly skilled, more knowledgeable, and longer-lived. This is the case precisely because technology has advanced, expanding our options and the ability to create better lives. Increasing the capabilities and efficiency of human technology is a great good, as better tools can be used to help us to become better in every way - to enable lives of more choice, greater capabilities, less suffering, and greater wealth."


The Pope is not in favor of engineering greater human longevity, a view put forward in his Easter homily:


"The Pope builds his position around three of the common, mistaken, knee-jerk objections to greater longevity: the Tithonus Error, predictions of stagnation, and the expectation of boredom. These and other objections are easily answered. One shouldn't expect a vested interest like the wealthy hierarchy of a modern organized religion to meaningfully engage the pro-longevity side of the debate, however. This will be to their detriment in the end: siding against medical progress and with the massive death and suffering caused by aging is a short term, conservative position for any organization, no matter how greatly they benefit from the status quo."


There is quite a concentration of biogerontologists, other aging researchers, advocates and funding sources for engineered longevity in the California Bay Area. A recent scientific meeting was covered by researcher Chris Patil:


"Today I'm attending the first Bay Area Aging Club at UCSF's Gladstone Institute. BAAC is a meeting of local scientists working in biogerontology and related fields ... The idea is that the conference will be held regularly (every 6 months or so), allowing frequent discussion of recent progress and ongoing work, and encouraging networking and collaboration between Bay Area biogerontologists. The conference is drawing from a fairly big population - everyone at the Buck Institute, comprising the members of 15 or so labs, and at least as many from Berkeley, Stanford, UCSF; I'd estimate more than 300 scientists."


The highlights and headlines from the past week follow below.

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Advanced glycation end-products (AGEs) seem to be important in aging, their buildup effectively a form of damage that harms cellular processes in a number of ways. Here, researchers suggest that an AGE precursor chemical is also problematic: "Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases."

This release via ScienceDaily summarizes the goals of present day calorie restriction research: "Organisms from yeast to rodents to humans all benefit from cutting calories. In less complex organisms, restricting calories can double or even triple lifespan. It's not yet clear just how much longer calorie restriction might help humans live, but those who practice the strict diet hope to survive past 100 years old. ... calorie restriction influences the same handful of molecular pathways related to aging in all the animals that have been studied. Aware of the profound influence of calorie restriction on animals, some people have cut their calorie intake by 25 percent or more in hopes of lengthening lifespan. [Researcher Luigi Fontana] is less interested in calorie restriction for longer life than in its ability to promote good health throughout life. ... Right now, the average lifespan in Western countries is about 80, but there are too many people who are only healthy until about age 50. We want to use the discoveries about calorie restriction and other related genetic or pharmacological interventions to close that 30-year gap between lifespan and 'healthspan.' However, by extending healthy lifespan, average lifespan also could increase up to 100 years of age."

A general interest article on transhumanist visions of the future and immortality in the sense of the continued repair and reversal of aging through medical technology: "Immortality could be sneaking up faster than we can believe. Barely a month goes by without some new advance in organ replacement, and a recent operation to replace a boy's windpipe with one generated from his own stem cells was called 'embarrassingly simple' by the specialist in charge. Further breakthroughs could be made by the SENS Foundation, led by the radical immortalist Aubrey de Grey, with a brutally simple plan to give humans an unbeatable protection against cancer. This involves limiting human cells' ability to divide at cancerous levels, with regular top-ups from externally grown cells replacing worn-out tissue. If these technologies can hold to their promise, biological immortality, perhaps the most cherished goal of the transhumanists, may be with us in a few decades. A loose grouping of scientists, philosophers and sympathisers, with organisations such as the Oxford Future of Humanity Institute and Humanity+, transhumanists urge human progress through radical technological enhancement. With regards to immortality, I'm certainly a sympathiser: if a dictator was murdering tens of millions of people right across the world, we'd gladly do anything to overthrow him. And yet ageing, as eloquently put by the transhumanist philosopher Nick Bostrom, is a tyrant that kills us by the cartload - and what do we do to stop it?"

It will be possible to replace the functions of some organs with machines in the near future, this advance accomplished on much the same timescale as the creation of tissue engineered replacement organs: "An artificial pancreas system that closely mimics the body's blood sugar control mechanism was able to maintain near-normal glucose levels without causing hypoglycemia in a small group of patients. The system, combining a blood glucose monitor and insulin pump technology with software that directs administration of insulin and the blood-sugar-raising hormone glucagon, was developed at Boston University (BU). The first clinical trial of the system was conducted at Massachusetts General Hospital (MGH) and confirmed the feasibility of an approach utilizing doses of both hormones ... Large doses of glucagon are used as a rescue drug for people with severely low blood sugar. Our system is designed to counteract moderate drops in blood sugar with minute doses of glucagon spread out throughout the day, just as the body does in people without diabetes." The future for this sort of technology is one of miniaturization, falling cost, and the possibility of incorporation into the body as an implanted device.

The Tithonus Error is the widespread and mistaken belief that extending the human life span will result in us being aged and decrepit for longer. This is not the case, however: engineered longevity can only be accomplished by repairing or reducing cellular and biochemical damage - which means you will be younger for longer. At In Search of Enlightenment, you'll find an examination of the roots of the Tithonus Error: "There is an irrational public predisposition to regard research on specific late-life diseases as marvelous but to regard research on aging, and thus all late-life diseases together, as a public menace bound to produce a world filled with nonproductive, chronically disabled, unhappy senior citizens consuming more resources than they produce. ... I am working on a new paper [that] examines how misperceptions about the present and future state of global health are themselves major obstacles to tackling aging. Because [imagined simulations of the future] are based on memories, medical research that proposes to eliminate a disease is much more likely to invoke hedonic experiences in our simulations then is a medical intervention that retards aging. ... our inability to make accurate, sensible simulations of what a future of retarding human aging would entail (for both the developed and developing world) is itself one of the greatest obstacles to prioritizing aging research. And this problem needs to be redressed."

From the University of Bristol: "Synthetic biology is about improving our ability to engineer biology, and to engineer biology you have to understand the underlying chemistry. ... We look at natural molecules and ask, 'How does nature do this?' And then we take those key features and build them into synthetic molecules to mimic the natural ones. ... Specifically, Woolfson is trying to capture features of the materials that hold cells together and which provide the environment to turn collections of cells into tissues such as skin, liver and networks of nerves. This 'glue' is called the extracellular matrix (ECM). However, the ECM is made up of large, complicated molecules with lots of different chemistries, so Woolfson began to investigate whether it would be possible to build something similar to ECM, but out of much simpler and more chemically accessible materials. That was 10 years ago. Today he has developed nano-sized proteins that have been designed to 'self assemble' into long, spaghetti-like strings, which then become entangled to form a gel. ... The result is a hydrogel (a gel in which the liquid constituent is water) made up of these tiny, spaghetti-like strings of proteins which acts as a scaffold to support cell growth in much the same way as the ECM does."

As illustrated by the reliability theory of aging, we are complex machines, and our life expectancy is a function of the pace at which we accumulate damage. For example, one contribution to rising life spans over the past century was the elimination of much of the burden of chronic disease throughout early life and middle age. Here, however, is an example of another, less common form of damage that nonetheless has the expected end result: "Although more children today are surviving cancer than ever before, young patients successfully treated in the 1970s and 80s may live a decade less, on average, than the general population ... The study, based on a computer model, is the first to estimate the lifetime toll of childhood cancer and the grueling but increasingly successful treatments for diseases such as kidney and bone cancers, leukemia, and brain tumors. About 10,000 children and adolescents are diagnosed with cancer annually, and the five-year survival rate has risen to about 80 percent overall. ... The study is based on how children were treated in the 1970s and early 1980s. It is our hope that when we see data from more recent cohorts of patients, there will be improved life expectancy as a result of some changes that pediatric oncologists have made."

WILT, ALT, AND ZSCAN4 (April 13 2010)
From the SENS Foundation: "To develop an unbreachable defense against cancer, SENS Foundation is pursuing the WILT (Wholebody Interdiction of Lengthening of Telomeres) strategy (OncoSENS) of systematically deleting genes essential to the cellular telomere-maintenance mechanisms (TMM) from all somatic cells, while ensuring ongoing tissue repair and maintenance through periodic re-seeding of somatic stem-cell pools with autologous TMM-deficient cells whose telomeres have been lengthened ex vivo. In addition to the deletion of one or more genes coding for essential element(s) of the telomerase holoenzyme, success will also require the deletion of some essential element of the machinery for the Alternative Lengthening of Telomeres (ALT) phenomenon, observed in a minority of cancer cells. Heretofore, the identity of that machinery has been elusive. Yeast cells have the ability to lengthen telomeres through a telomerase-independent mechanism involving telomere recombination, and there has been evidence for some time suggesting that ALT cancers lengthen telomeres through a similar process." The article goes on to look in detail at one plausible candidate mechanism for ALT, and how this new knowledge might be incorporated into WILT.

How is it possible for evolutionary selection to favor genetic variants beneficial in human old age, long after reproduction is impossible? An open access paper examines this question: "Evidence points towards the existence of a strong heritable component of human longevity. Around a quarter to a third of the variability of lifespan can be attributed to the action of genes. One of the best examples of a gene affecting survival in old age is the apolipoprotein E gene APOE. ... One of the major ideas in the evolutionary theory of ageing is the suggestion that, because the force of natural selection declines with age, alleles with deleterious effects seen only at older ages can reach higher frequencies than those that have their effects earlier in life. Therefore, if a gene exerts an effect only after the end of the reproductive phase of the lifespan it has been thought unlikely that it could have been subject to significant direct selection pressure ... It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible."

Via EurekAlert!, another example of testing stem cells and heart regeneration: "Some patients with heart muscles seriously affected by coronary heart disease may soon be able to benefit from an innovative treatment. Researchers [are] evaluating the safety, feasibility and efficacy of injecting stem cells into the hearts of patients while they are undergoing coronary bypass surgery. These stem cells could improve healing of the heart and its function. The IMPACT-CABG (implantation of autologous CD133+ stem cells in patients undergoing coronary artery bypass grafting) protocol evaluates this experimental procedure, which is destined for patients suffering from ischemic heart disease, in which the blood supply to the heart is decreased and associated with heart failure. These patients undergo open-heart coronary bypass surgery, performed by the medical team to improve perfusion of the heart muscle. A few weeks ago, the first patient received progenitor CD133+ stem cells isolated from his bone marrow and enriched, [and] has been doing very well ever since. Already, improvement has been noted in the contraction capacity of his heart, which has improved its ability to pump blood."



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