Longevity Meme Newsletter, February 25 2008

February 25 2008

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.



- What Is Wealth?
- Why Repairing Aging is Easier Than Slowing Aging
- Discussion
- Latest Healthy Life Extension Headlines


Some non-standard thoughts on choice, longevity and what wealth really means:


"What is wealth? Let me try a slightly non-standard answer to that question. Wealth is a measure of your ability to do what you would like to do, when you would like to do it - a measure of your breadth of immediately available choice.

"Time spent alive, measured in the ticking of heartbeats, is more than valuable - it is wealth itself, the source of all other measures of wealth. All property was created by someone, somewhere, taking their time. The creation and exchange of property is a way to make time fungible, transferrable, a more valuable resource. Time spent alive is the root of all property, all human action, and thus all wealth - both the silver in your pocket that provides for present choice, and the wealth of possible choices created by past investment."


The most important debate - and research initiatives to reinforce points within that debate - presently taking place within the biogerontological community is over the best course to extend the healthy human life span. On the one side, those who want to slow aging by reengineering our genome and metabolism to be more resistant to damage. On the other side, those who want to reverse aging by repairing the identified differences between old tissue and young tissue in the metabolism we have today. More on this topic in the following Fight Aging! post:


"Biology is complicated. We are built out of a million evolutionary optimizations, and evolution loves the reuse of component parts. Every newly evolved mechanism will quickly find its place in other evolved systems, while still being used in its original capacities. The human cell is a big cat's cradle of macromolecules, each with twenty-something different purposes, operating in interacting feedback loops and dynamically regulated processes.

"This hyperconnectivity and reuse of processes, proteins and genes, this rampant complexity, is why aging researchers who focus on metabolic and genetic engineering - which is to say the bulk of the field - see healthy life extension as hard, and any meaningful progress in terms of additional decades as remote in the future."

It is hard for the metabolic engineers because every possibly beneficial change to genes or metabolic pathways tugs on a hundred connections to other vital processes. Engineering metabolism implies building and ratifying a new, complex system while still lacking a full understanding of the complex system you have right now. It will be very hard, and researchers are a long way from any significant progress.

This is precisely why the repair approach - reversing changes - is more feasible for near-term progress. The reversal of aging by repairing and reversing specific biochemical changes amounts to an attempt to move a presently failing system back to the state that you already know works. Full understanding of the workings of the system is helpful but not required - that we know it works is enough. What we need instead is the much less complex list of differences between an aged biochemistry and a young biochemistry. These differences are already known, enumerated by the many arms of the scientific community over the past decades:


Good engineering is all about working with present knowledge to produce good results in the best possible time and cost - to be clever enough to sidestep ignorance and unnecessary work. We already have working examples of a youthful, healthy metabolism, and so it makes little sense to go to the great efforts required in order to produce new metabolic configurations to slow aging. We already know the changes that separate young tissue from old tissue. It is more effective, more efficient and more sensible to work towards reversing the biochemical changes of aging in the metabolism we have today than to set forth on the long, hard road to produce a more slowly aging human.


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!




To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

Towards Regenerative Therapies For the Liver (February 22 2008)
Folk at Advanced Cell Technology are touting their latest technology demonstration: "a robust and highly efficient process for the generation of high-purity hepatocytes (liver cells). ... Highly enriched populations of definitive endoderm (DE) were generated from [human embryonic stem cells (hESCs)] and then induced to differentiate along the hepatic lineage by the sequential addition of inducing factors implicated in physiological hepatogenesis. The differentiation process was largely uniform with cell cultures progressively expressing increasing numbers of hepatic lineage markers. The hepatocytes exhibited functional hepatic characteristics such as glycogen storage, indocyanine green uptake and release, and albumin secretion. In an animal model of acute liver injury, the hESC-DE cells differentiated into hepatocytes and successfully repopulated the damaged liver. ... the research represents another one of Advanced Cell Technology's efforts aimed at the large-scale differentiation of human embryonic stem cells [into] critical replacement cell types."

On Porcine Xenotransplants (February 22 2008)
From the perspective of 2008, it seems plausible that xenotransplantion could become economically competitive with stem-cell based tissue engineering of replacement organs for long enough to become widespread. Competition is good - it drives people to achieve more, faster. "Alternatives to the use of human organs for transplantation must be developed and these alternatives include stem cell therapy, artificial organs and organs from other species, i.e. xenografts. For practical reasons but most importantly because of its physiological similarity with humans, the pig is generally accepted as the species of choice for xenotransplantation. Nevertheless, before porcine organs can be used in human xenotransplantation, it is necessary to make a series of precise genetic modifications to the porcine genome, including the addition of genes for factors which suppress the rejection of transplanted porcine tissues and the inactivation or removal of undesirable genes which can only be accomplished at this time by targeted recombination and somatic nuclear transfer."

The Source of Age-Related Diabetes (February 21 2008)
How is it that eating too much eventually leads to insulin resistance, diabetes and a shorter life? Just as scientists are making progress in uncovering the biomechanisms of calorie restriction, they are also showing how excess food causes its predictable effects: "For quite some time now, scientists suspected the so-called hexosamine pathway - a small side business of the main sugar processing enterprise inside a cell - to be involved in the development of insulin resistance. ... For the first time we have a real understanding of how the insulin signaling system is turned on and off ... researchers believe that the hexosamine pathway acts as fuel gauge, protecting the body's cells against the toxic effects of too much glucose and other high-energy molecules. Excessive quantities of nutrients - the result of a lifestyle where food is plentiful and exercise is optional - [dampen] the insulin response, paving the way for a relentless progression of insulin resistance. ... the enzyme OGT [is] the last in a line of enzymes that shuttle sugars through the hexosamine pathway. ... when [researchers] put OGT into overdrive in the livers of mice, the animals developed insulin resistance and abnormal blood lipid levels, emphasizing the importance of the hexosamine pathway for the development of insulin resistance, the first step towards full-blown type 2 diabetes." A step on a path you can choose not to follow, needless to say.

Quantifying Progress in Treating Cancer (February 21 2008)
Cancer is the great bugbear of aging, the mechanisms of your biology slipped into destructive ways. But even before the development of the cancer cures of future decades, cancer will become a merely unpleasant chronic condition - a tax on your wallet rather than your life. EurekAlert! notes the progress made to date, even as the population ages, and even prior to the introduction of impressive next generation therapies presently in trials and the laboratory: "death rates from cancer in the United States have decreased by 18.4 percent among men and by 10.5 percent among women since mortality rates began to decline in the early 1990s ... for the number of cancer deaths to decrease, the decline in the overall cancer mortality rate must be large enough to offset the increasing numbers due to growth and aging of the population." Take the policy mumbo jumbo in the article with a grain of salt: it is progress in medical technology - and resulting lowered cost and increased effectiveness of existing techniques - that underlies the drop in death rates for many age-related conditions.

More Cancer Immunotherapy (February 20 2008)
The broad heading of "immunotherapy" covers a very wide range of efforts to convince the immune system to attack specific cells. Here's another example of using viral vectors to induce immune cells into specific actions: "The researchers used a virus stripped of its disease-causing genes as a vehicle to deliver two therapeutic proteins directly into the [glioblastoma multiforme (GBM)] tumor cells. One protein, FMS like tyrosine kinase 3 ligand (Flt3L), drew dendritic cells into the brain. Another protein, herpes simplex virus type 1 thimidine kinase (HSV1-TK), combined with the antiviral gancyclovir (GCV), killed tumor cells. Dendritic cells clean up debris from dying cells and in the process alert immune system cells of the existence of foreign entities, or antigens - in this case, GBM cells. Newly 'educated' immune system cells then swarm to the tumor cells to destroy them. In an earlier study, [researchers] used HSV1-TK and GCV alone to treat GBM and found that about 20 percent of the animals survived, compared to controls. By adding the dendritic-cell inducing Flt3L, the survival rate jumped to about 70 percent. Systemic immune activity was sustained, even fending off a 're-challenge' with additional tumor cells."

Embryonic Stem Cells Versus Stroke Damage (February 20 2008)
Via EurekAlert!, work on repairing neural damage following stroke: "Neural cells derived from human embryonic stem cells helped repair stroke-related damage in the brains of rats and led to improvements in their physical abilities ... [researchers hope] the cells from this study can be used in human stroke trials within five years. ... At the end of two months, the cells had migrated to the damaged brain region and incorporated into the surrounding tissue. None of those transplanted cells formed tumors. Once in place, the replacement cells helped repair damage from the induced stroke. The researchers mimicked a stroke in a region of the brain that left one forelimb weak. This model parallels the kinds of difficulties people experience after a stroke. Testing at four weeks and again at eight weeks after the stem cell transplants showed the animals were able to use their forelimbs more normally than rats with similarly damaged brain regions that had not received the transplants."

Getting to the Future of Engineered Biology (February 19 2008)
A rather interesting article from Edge, which looks at how we might get from where we are today in biotechnology to the future we'd all like to see. It's very much along the lines of earlier discussions at Fight Aging! on open source biotech and the cost of infrastructure as they relate to progress and research communities: "How can I make biology easy to engineer? ... Going back hundreds of years, people had imagined that you could always design and build or make life, but nobody could really do that much about it. ... Now, 30 years after the initial successes of biotechnology, it has only realized really one of the early promises. ... Nevertheless, biotechnology exists, it's a huge positive contributor to our health and economy and the human condition generally, and now it's 2008. And so the question is, can we realize the initial promise of biotechnology? Or, forget that question, how do we make biology easy to engineer, so that anything we might want to manufacture out of the living world is something that we can pull off? ... Are we going to ever get to the point where it's not an exclusive technology, it's not a technology that requires experts? Are we ever going to get to the point where we can make many component integrated systems?"

The Latest Rejuvenation Research (February 19 2008)
The latest issue of the journal Rejuvenation Research is available online. Most of you skip the cover blurb, I'm sure, but it's worth noting: "Rejuvenation Research publishes cutting-edge work on rejuvenation therapies in the laboratory and clinic, as well as the latest research relevant to what these novel therapeutic approaches must do at the molecular and cellular level in order to be truly effective. Aubrey de Grey, at the helm of this multidisciplinary peer-reviewed journal, seeks to understand and ultimately defy the mechanisms of aging. He was featured in a recent 60 Minutes segment titled 'The Quest for Immortality'; in a cover story on de Grey, MIT's Technology Review said, 'His tireless efforts...have put him among the most prominent proponents of antiaging science in the world. ... De Grey has become more than a man; he is a movement.' Dr. de Grey and his outstanding international editorial board have the opportunity to further explore and advance the science, and perhaps achieve the ultimate goal of slowing or reversing the process of aging."

An Overview of Calorie Restriction (February 18 2008)
Via the St. Louis Post-Dispatch, a decent overview of the practice of calorie restriction and some present scientific efforts to quantify effects on health and aging: "Early tests showed the practitioners, who call themselves 'CRONies,' (Calorie Restriction, Optimal Nutrition), had virtually no risks of cardiovascular disease or cancer ... It's becoming clear from studies with the CRONies - and from this brief, prospective study - that calorie restriction does change some of the markers we associate with aging ... Proponents of calorie restriction, which they call 'CR,' boast of disappearing triglycerides, healthy cholesterol levels, the elimination of low-level inflammation through the body caused by oxidation damage, lowered and more stable blood sugar, nonexistent cardiovascular disease and even instances of being cured of early stage diabetes. ... The attraction to CR by researchers was sparked by more than 60 years of uncommonly consistent tests on laboratory mice and rats. [When] laboratory animals were placed on calorie restricted diets, 'their life spans increased 20 to 40 percent.'" The quality of media examination of calorie restriction has greatly increased in past years thanks to the efforts of advocates and educators in the community.

Kurzweil's Vision of Accelerating Longevity (February 18 2008)
This Living on Earth transcript gives a concise look at the view of future longevity outlined by Ray Kurzweil in Fantastic Voyage: "there are three bridges, to dramatically extending our life - to radical life extension. ... only 10-15 years from now [we'll] have bridge two which [is] the full-flowering of the biotechnology revolution where we'll have the means of re-programming our own biology. ... health and biology and medicine are becoming information technologies, they are subject to what I call the 'Law of accelerating returns' which is this doubling of the power of these technologies every year. ... Bridge Three is nanotechnology. ... within about 20 years we will have fully reverse-engineered biology. We will have the means through biotechnolgy and nanotechnology to fix anything that goes wrong - ultimately at the cellular level and at the molecular level - with nanobots going inside our body and fixing each cell as something goes wrong. And that would really enable us to live indefinitely - it's a little bit different than a guarantee, I mean you could end up in an explosion somewhere or something. But it will really extend our human longevity indefinitely." I'm amongst those who think Kurzweil's projections are aggressive - but only by a decade or two.



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