Advances in biotechnology are greatly reducing the cost of performing broad analyses of metabolism - and so researchers are gathering ever more data on the various breeds of long-lived mice that have been created in recent years: "Significant advances in understanding aging have been achieved through studying model organisms with extended healthy lifespans. Employing (1)H NMR spectroscopy, we characterized the plasma metabolic phenotype (metabotype) of three long-lived murine models: 30% dietary restricted (DR), insulin receptor substrate 1 null (Irs1(-/-)), and Ames dwarf (Prop1(df/df)). A panel of metabolic differences were generated for each model relative to their controls, and subsequently, the three long-lived models were compared to one another. Concentrations of mobile very low density lipoproteins, trimethylamine, and choline were significantly decreased in the plasma of all three models. Metabolites including glucose, choline, glycerophosphocholine, and various lipids were significantly reduced, while acetoacetate, d-3-hydroxybutyrate and trimethylamine-N-oxide levels were increased in DR compared to ad libitum fed controls. Plasma lipids and glycerophosphocholine were also decreased in Irs1(-/-) mice compared to controls, as were methionine and citrate. In contrast, high density lipoproteins and glycerophosphocholine were increased in Ames dwarf mice, as were methionine and citrate. Pairwise comparisons indicated that differences existed between the metabotypes of the different long-lived mice models. Irs1(-/-) mice, for example, had elevated glucose, acetate, acetone, and creatine but lower methionine relative to DR mice and Ames dwarfs. Our study identified several potential candidate biomarkers directionally altered across all three models that may be predictive of longevity but also identified differences in the metabolic signatures. This comparative approach suggests that the metabolic networks underlying lifespan extension may not be exactly the same for each model of longevity and is consistent with multifactorial control of the aging process."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22225495

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A possible method of boosting muscle repair, and thus treating muscle wasting conditions - such as the sarcopenia that attends aging: "a lipid signaling molecule called sphingosine-1-phosphate or 'S1P' can trigger an inflammatory response that stimulates the muscle stem cells to proliferate and assist in muscle repair. ... mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, exhibit a deficiency of S1P, [and] boosting their S1P levels improves muscle regeneration ... The ability of muscles to regenerate themselves is attributed to the presence of a form of adult stem cells called 'satellite cells' that are essential for muscle repair. Normally, satellite cells lie quietly at the periphery of the muscle fiber and do not grow, move or become activated. However, after muscle injury, these stem cells 'wake up' through unclear mechanisms and fuse with the injured muscle, stimulating a complicated process that results in the rebuilding of a healthy muscle fiber. S1P is a lipid signaling molecule that controls the movement and proliferation of many human cell types. ... S1P is able to 'wake up' the stem cells at the time of injury. It involves the ability of S1P to activate S1P receptor 2, one of its five cell surface receptors, leading to downstream activation of an inflammatory pathway controlled by a transcription factor called STAT3. [This results] in changes in gene expression that cause the satellite cell to leave its 'sleeping' state and start to proliferate and assist in muscle repair. ... If these findings are also found to be true in humans with Duchenne Muscular Dystrophy, it may be possible to use similar approaches to boost S1P levels in order to improve satellite cell function and muscle regeneration in patients with the disease. Drugs that block S1P metabolism and boost S1P levels are now being tested for the treatment of other human diseases including rheumatoid arthritis. If these studies prove to be relevant in Duchenne patients, it may be possible to use the same drugs to improve muscle regeneration in these patients. Alternatively, new agents that can specifically activate S1P receptor 2 could also be beneficial in recruiting satellite cells and improving muscle regeneration in muscular dystrophy and potentially other diseases of muscle."

Link: http://www.sciencedaily.com/releases/2012/05/120515070307.htm

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The BBC here looks briefly at the study of aging in varying animal species - it mangles the scientific details in the usual fashion, but covers much of the territory: "From the moment they are born into the dense jungle of Central Africa, the biological clock is ticking for baby bonobos. A recent study, published in the journal Science, revealed that all primates - from men to monkeys - roughly age in the same way, with a high risk of dying in infancy, a low risk of dying as juveniles and then an increasing risk of dying as they aged. Some species though, have found a few tricks to help them play the aging game and extend their natural lifespans. By doing so, they can live for hundreds of years. While a select few, by some definitions, may already have become immortal. ... some species of bat [can] live for decades [and] the explanation may lie in the way bats protect themselves from protein damage, using special molecules called protein chaperones. ... Studies of the American lobster (Homarus americanus), have shown that its extreme longevity might be related to the expression of telomerase ... High concentrations of telomerase are found in cells that need to divide regularly such as organs and embryonic stem cells. Access to an elevated supply of telomerase would equip this crustacean with the ability to rebuild cells damaged by aging. The ability to repair cells in this way may help to explain why lobsters can live up to 100 years and are able to regrow limbs even at an 'old age'. ... Another oceanic resident, the quahog clam (Arctica islandica), is thought to be one of the longest lived metazoans of all. A recent study on this ancient clam, [which] lives more than 400 years, shows it has an increased resistance to oxidative stress. ... The reasons for the exceptional longevity in Arctica may have little to do with resistance to oxidative stress though. ... Instead, like in naked mole rats, it may be the integrity of the animal's proteins that may be the key, rather than damaging free radicals or antioxidants used to defend against them."

Link: http://www.bbc.co.uk/nature/12733853

The activity and changing configuration of the immune system is intimately connected with aging in a number of ways. In early life, exposure to infections that require an energetic immune response in effect burns your candle faster by generating more biochemical damage to your body in the process of defending it from the effects of disease. In later life, when the immune system runs beyond its evolutionary warranty, it falls into a state of constant, futile activation and damage - and that damage also adds up.

When you look at the reliability theory of aging, or any like consideration of aging as the consequences of accumulating damage to a complex system, it becomes clear that the immune system is an important component in the model. For example, it is generally accepted that much of the improvement in life expectancy over past centuries stems from a reduction in infectious disease - a process that is by no means complete, given what we still suffer from quiet, persistent infections like cytomegalovirus. But fewer infections mean less activation of the immune system in early life and less damage carried into later life. That leads to both improved health, a physiologically younger body at a given chronological age - and an immune system that declines more slowly, and later in life.

Here is an open access paper in which researchers directly demonstrate (in insects) the principle that early immune activity means a shorter life expectancy:

The pathology of many of the world's most important infectious diseases is caused by the immune response. Additionally age-related disease is often attributed to inflammatory responses. Consequently a reduction in infections and hence inflammation early in life has been hypothesized to explain the rise in lifespan in industrialized societies.

Here we demonstrate experimentally for the first time that eliciting an immune response early in life accelerates ageing. We use the beetle Tenebrio molitor as an inflammation model. We provide a proof of principle for the effects of early infection on morbidity late in life and demonstrate a long-lasting cost of immunopathology.

Like many investigations into the roots of aging, this is more a pointer towards areas where future development of rejuvenation biotechnology should focus than something of direct and immediate use. Results like this add more weight to work on reversing damage in the immune system, and preventing the immune system from falling into a chronic inflammatory state. There isn't anything we can do about our past exposure to infection and persistent agents like cytomegalovirus, but we can help to accelerate the development of ways to fix the resulting damage that we carry with us.

The liver has the greatest capacity for regeneration amongst human organs - but there's always room for improvement. Here, cancer researchers incidentally uncover a potential mechanism to safely boost regenerative capacity: "During chronic liver damage repetitive waves of hepatocyte cell death and compensatory proliferation take place, eventually culminating in chronic liver failure and often in the development of hepatocellular carcinoma (HCC). A misregulated regenerative response to chronic liver injury may represent the base for development of HCC. Therefore, a more detailed understanding of signaling pathways involved in proliferation control of hepatocytes not only holds the great promise of informing new therapies to increase the hepatic regenerative potential but also to deduce new strategies for the treatment of HCC. We have established a unique system to perform in vivo RNAi screens to genetically dissect cellular signaling networks regulating hepatocyte proliferation during chronic liver damage. ... we identified shRNAs which showed strong enrichment during regeneration, therefore pinpointing new regulators of liver regeneration. Our top scoring candidate represents a kinase, which is accessible to pharmacological inhibition. Functional in vivo validation studies show that stable knockdown of the candidate gene by different shRNAs can significantly increase the repopulation efficiency of mouse hepatocytes and also increases the regenerative capacity of chronically damaged mouse livers. Despite the fact that some human HCCs show focal deletion of the candidate gene, a therapeutic window for regenerative therapy exists, as mice stably repopulated with shRNAs against the candidate did not develop liver tumors."

Link: http://www1.easl.eu/easl2011/program/Orals/261.htm

The Methuselah Generation is a documentary film in progress, far enough along that the filmmaker is putting out early versions: "Is aging a disease that can be cured? Is it possible to live forever? Even if we could, should we? The Methuselah Generation (working title) is a 3D verite documentary about the science and philosophy of Life Extension - the scientific hypothesis that individuals may be capable of extending human life beyond anything humans have yet imagined. The story will follow a select few individuals at the forefront of this movement as well as those skeptical and antagonistic toward the goals of life extension. The film will follow five protagonists as they progress with their movement to change humanity. Through intimate interviews, observational shooting and provocative imagery, this character-based 3D documentary will explore the big philosophical ideas of Life Extension, while also examining the scientific feasibility - the film will explore the what, how and (most significantly) the WHY of long-lived humans."

Link: http://davidalvarado.info/le.html

I don't see anything wrong with standing up and arguing passionately for the merits of either immortality as a Platonic ideal or immortality as a practical goal. Here I take the colloquial modern meaning of agelessness attained through biotechnology rather than the old-school "never die, ever" variety of immortality attained only in stories and myths. But someone has to be out there pushing out the boundaries of the discussion:

The middle of the road, "reasonable" position in public or political debate tends to gravitate to midway between what are perceived to be the two opposite outrageous extremes, regardless of the actual merits of any of these positions. With this in mind, it is occurring to me that part of the ongoing problem in the modern political debate over healthy life extension is that our "outrageous extreme" has always been a tentative, reasonably proposal that medical research carry on and that near-term technology would seem to allow us all to live a little longer ... say, to 150.

Public discourse is an arena of the timid, people who build their own cage of narrow visions and incremental goals. Without loud visionaries coming along to rattle the bars and point to the mountains in the distance, nothing would ever get done. Live to 150? Peanuts. If we enacted the goals of SENS, producing a rejuvenation biotechnology toolkit to repair the biochemical damage of aging, we'd all live for thousands of years if the present rate of fatal accidents continued as-is.

So I'm always pleased to see people putting out opinions like this and provoking resulting discussions like this one at Hacker News:

I want to live forever. I've always thought that not dying was a pretty obvious thing to want. To my surprise, I've found that a lot of people whom I usually agree with on most topics strongly disagree with me on this one. Rather than write yet another piece extolling the virtues of a far-future post-scarcity post-singularity world, I thought I'd just document some of the objections to immortality I get and my counterarguments.

Note that for the purposes of giving my conversational partners opportunities to disagree, I typically posit a form of immortality where you, and you alone are presented with the option of eternal youth with no suicide option. You constantly regenerate to perfect health at the prime of your life. There are a lot of potential ways we might go about not dying, but people tend to find objections to this particular flavor more readily than the others. Please assume this working definition for the below.

Even discussion of the platonic ideal of immortality is, I think, useful provocation against the backdrop of advancing biotechnology that will be able to extend the human lifespan significantly in decades to come. Those advances won't happen by themselves: people need to work on them, support them, and demand them. An economy of longevity-enhancing biotechnology must arise, and for that there needs to be - at a minimum - a whole lot more people talking and thinking about the prospects.

Research suggests that changes in messenger RNA (mRNA) translation - a step in the complex process by which proteins are built from the blueprint of a gene - are important in the metabolic determination of longevity. This appears to be one of the ways in which the TOR gene, and thus rapamycin, influences longevity: "Appropriate regulation of mRNA translation is essential for growth and survival and the pathways that regulate mRNA translation have been highly conserved throughout eukaryotic evolution. Translation is controlled by a complex set of mechanisms acting at multiple levels, ranging from global protein synthesis to individual mRNAs. Recently, several mutations that perturb regulation of mRNA translation have also been found to increase longevity in three model organisms: the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Many of these translation control factors can be mapped to a single pathway downstream of the nutrient responsive target of rapamycin (TOR) kinase. [This suggests] that mRNA translation is an evolutionarily conserved modifier of longevity and [could] influence aging and age-associated disease in different species."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20886753

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

You might recall that the olm (Proteus anguinus) is a type of small salamander that lives as long as we do. Here researchers point out that olm life span is inconvenient for some theories of aging: "Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories." Yet there are still the studies demonstrating extended life span through targeting antioxidants to mitochondria, which imply that at least so far as those cellular structures are concerned, oxidative damage is very important. It may be that the olm, like naked mole rats, has mitochondria that are highly resistant to damage in comparison to other species.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21290398

The modest goals of the mainstream longevity science community are outlined by one of its members in this article - to enable everyone to age as slowly as only some people presently do. No radical life extension or rejuvenation, as would be enabled by the damage repair approach to longevity science, but rather just a gentle slowing of aging, enabled by technologies that would probably not emerge in time to benefit those of us in middle age today. "It is the aging of our cells that causes us to develop most diseases, says Dr. Nir Barzilai, professor of medicine and genetics at the Albert Einstein College of Medicine in New York. 'We know this, paradoxically, because of the amazing success we have had in treating heart disease. We have been able to save people from heart attacks with stents and bypass surgery - only to find that within a year or two they develop Alzheimer's, diabetes or cancer at an alarming rate. Why? Because we have never treated the underlying aging of their cells. We have simply treated the disease manifestation.' So, explains Barzilai, if we can find the processes in the body that control aging and find a way to treat them, we will be able to protect people from the diseases of aging. Barzilai heads a unique longevity study of more than 500 people who have reached the age of 100. The LonGenity study is looking at the genetic makeup of centenarians to identify the biological markers that explain why they live so long and so well. Because the remarkable thing about these people is not simply that they live to the age of 100, it is that they live to 100 in pretty good health. Just why they live that long without getting sick and dying is what Barzilai wanted to find out."

Link: http://www2.macleans.ca/2011/03/17/living-like-a-centenarian/

Researchers continue to make progress in scaffolding materials that enable the body to regrow missing bone: "In contrast to long-term solutions based on titanium, degradable implants are intended to replace the missing pieces of bone only until the fissure closes itself up. That may last months or even years, depending on the size of the defect, the age and health status of the patient. A new implant improves the conditions for the healing process. It emerged from the "Resobone" project of the federal ministry for education and research, and is sized-to-fit for each patient. Unlike the conventional bony substitutes to date, it is not made up as a solid mass, but is porous instead. Precise little channels permeate the implant at intervals of just a few hundred micrometers. ... The porous canals create a lattice structure which the adjacent bones can grow into. ... the Resobone implants will primarily replace missing facial, maxillary and cranial bones. Currently, they are able to close fissures of up to 25 square centimeters in size. ... The patient's computer tomography serves as the template for the precision-fit production of the implants. The work processes - from CT imaging, to construction of the implant, through to its completion - are coordinated in such precise sequences that the replacement for a defective zygomatic bone can be produced in just a few hours, while a five-centimeter large section of cranium can be done overnight."

View the Article Under Discussion: http://www.fraunhofer.de/en/press/research-news/2010/06/bone-replacement-laser-melting.jsp

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

In a nutshell, this is why research into so-called accelerated aging conditions may be relevant to longevity science: "One of the many debated topics in ageing research is whether progeroid syndromes are really accelerated forms of human ageing. The answer requires a better understanding of the normal ageing process and the molecular pathology underlying these rare diseases. Exciting recent findings regarding a severe human progeria, Hutchinson-Gilford progeria syndrome, have implicated molecular changes that are also linked to normal ageing, such as genome instability, telomere attrition, premature senescence and defective stem cell homeostasis in disease development. These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process." This same viewpoint - that each of the accelerated aging conditions represents a different facet of normal aging run wild - holds up for well other conditions, such as Werner syndrome, given the evidence amassed to date.

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20651707

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Here another study of the long-lived confirms the common wisdom: "Objectives: To identify predictors of extraordinary survival. Design: Longitudinal study of a cohort of elderly people followed up until almost all have died. Setting: Two counties in Iowa; a part of the Established Populations for Epidemiologic Study of the Elderly. Participants: Two thousand eight hundred ninety community-dwelling citizens aged 65 to 85 at baseline and surviving at least 3 years. Measurements: Data relating to age, sex, birth order, parental longevity, marital status, education, family income, social support, self-reported health, chronic diseases, blood pressure, body mass index, physical ability, exercise, life attitude and mental health were obtained. Extraordinary survivors (ESs) were defined to include approximately 10% of the longest survivors in their sex group. Results: The 253 ESs were far more likely never to have smoked. In models adjusted for age, sex, and smoking, the earlier-life factors such as parental longevity, being earlier in the birth order (in women only), and body mass index at age 50 were associated with extraordinary survival. In similar models for predictors at age 65 to 85, extraordinary survival was associated with excellent self-reported health, fewer chronic diseases, better physical mobility and memory, and positive attitude toward life, but it was not associated with depression, anxiety, or sleep quality. In multivariable models, attitude toward life was not an independent predictor. Women in the top third of a cumulative score of independent predictors were 9.3 times as likely to reach extraordinary survival as those in the bottom third. Conclusion: ESs had fewer 'classical' risk factors and were in better health than their contemporaneous controls. Possibly genetic factors such as parental longevity and birth order appear to be less predictive in men than in women."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21649635

Another example of simultaneously boosting life span and reducing cancer in mice in the laboratory - not maximum lifespan, however, or the paper would be much more triumphant. This is the first I've seen of this particular mechanism, so your guess is as good as mine as to what is going on under the hood. Once thing I'm pleased to note is that the researchers controlled for calorie restriction, and considered it important enough to state as much in the abstract. That's progress: "Sulfate (SO(4)(2-)) plays an important role in mammalian growth and development. In this study, hyposulfatemic NaS1 null (Nas1-/-) mice were used to investigate the consequences of perturbed SO(4)(2-) homeostasis on longevity. Median life spans were increased (by ?25%) in male and female Nas1-/- mice when compared with Nas1+/+ mice on identical food intakes. At 1yr of age, serum SO(4)(2-) levels remained low in Nas1-/- mice (?0.16mM) when compared to Nas1+/+ mice (?0.96mM). RT-PCR revealed increased hepatic mRNA levels of Sirt1 (by ?60%), Cat (by ?48%), Hdac3 (by ?22%), Trp53 and Cd55 (by ?36%) in Nas1-/- mice, genes linked to ageing. Histological analyses of livers from 2yr old mice revealed neoplasms in >50% of Nas1+/+ mice but not in Nas1-/- mice. This is the first study to report increased lifespan, decreased hepatic tumours and increased hepatic expression of genes linked to ageing in hyposulfatemic Nas1-/- mice, implicating a potential role of SO(4)(2-) in mammalian longevity and cancer."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21651971

Open Cures is an initiative that aims to accelerate the development of existing longevity-enhancing biotechnologies demonstrated in the laboratory, but which are not being developed for commercial use in humans - largely due to regulatory barriers.

Open Cures is a volunteer initiative, open to everyone willing to help, that aims to speed the advent of biotechnologies that can slow down or repair aspects of the biological damage of aging and thus extend healthy human life. Our primary long-term goal is to bring together (a) promising but undeveloped biotechnologies of longevity and (b) the developers who can bring them to the clinic.

A fellow named Allen is one of the folk whose interest in the Open Cures vision convinced me that I needed to do more than just talk about it: you can see his comments on the old Vegas Group posts here at Fight Aging!, which contain the ideas that led to Open Cures.

The first phase of the Open Cures initiative aims to produce detailed documentation of existing forms of longevity biotechnology from the laboratory, as that documentation is a necessary precursor to bringing these potential foundations for future therapies to a wider audience. One of these nascent-but-demonstrated biotechnologies is mitochondrial protofection: a way to introduce new and undamaged mitochondrial DNA (mtDNA) into mitochondria in an attempt to repair the accumulated defects they bear - defects which contribute meaningfully to aging. You'll want to look back in the Fight Aging! archives for an introduction to that topic.

Mitochondria go bad as a natural consequence of their operation, and if enough go bad in the right way, and manage to escape the natural recycling mechanisms of the cell, then they take over that cell - causing it to malfunction, damage its surroundings, and release harmful reactive molecules that are carried throughout the body. Given enough cells doing this, you will become frail and eventually die as vital systems in your body become too damaged to operate correctly.

Since the launch of Open Cures, Allen has been looking into the published papers on mitochondrial protofection and writing up an outline for a protocol - the detailed step by step instructions that allow a technique in biotechnology to be replicated. The work to date can be found in the Open Cures wiki:

"Protofection" is a word coined by a group of scientists at the University of Virginia. It is the name they have given to a procedure they were developing which could possibly become a way to rejuvenate malfunctioning mitochondria by providing them with a new, undamaged genome.

I have been attempting to write a detailed set of instructions that would allow someone with sufficient knowledge and means to reproduce their work. So far I've come up with a bare-bones skeleton or scaffolding upon which a more experienced and better writer can build - adding detail, correcting errors, and making it more understandable. ... Corrections, additions, improvements, and comments are very welcome.

The next stage in this documentation project, one of many to come, is to find writers - such a grad-level life science students willing to freelance at reasonable rates - to flesh it out into as full a protocol document as can be built from the present state of published scientific work on protofection.

Two of the interesting items we discovered in the course of researching protofection more closely are that (a) a number of research groups attempted to replicate mitochondrial protofection over the past five years but met with no success, and (b) the scientists who initially demonstrated protofection have not yet published a clear explanation of the transcription factor used as a tool when introducing replacement DNA into mitochondria:

TFAM refers to human mitochondrial transcription factor A. This protein plays several roles in the mitochondria. It participates in mtDNA transcription, replication and maintenance. It also non- specifically binds to mtDNA which is the property we want to exploit as we attempt to pull pristine mtDNA into mitochondria which contains damaged DNA

[Missing details: We need to provide the DNA sequence in the format used by DNA synthesis machines. The DNA sequence must be verified as accurate. If we make a mistake here, which would be easy to do, the entire experiment is useless. The amino acid sequence is provided in the 2008 paper and the DNA sequence could be deduced from that, but there are some complications.

A. The published amino acid sequence may not be accurate. For one thing, a ")" symbol appears in the sequence and I have no idea what that means. Also the sequence contains an unusual repeated chain of amino acids which I suspect was not really part of the protofection protein.

B. The DNA will also have to be modified by adding a short sequence to each end of it. These two short sequences must each contain a site that can be cut by EcoI, the restriction endonuclease that will be used to prepare the DNA to be spliced into the bacterial plasmid that will be used later.

C. We also have to carefully check the DNA sequence to be sure that another EcoI restriction site is not found somewhere in the middle of the sequence.]

This second point, the missing definition, doesn't matter as much as you might think for the purposes of producing a good protocol document. When we do eventually find out the correct DNA sequence for the modified TFAM, it will be the work of moments to update the published document, and none of the other materials need to change.

I see this missing information as one good example as to why an initiative like Open Cures is both necessary and helpful: there are gaps that need filling in all these scientific publications and procedures, left there (intentionally and otherwise) because these works are not intended for a wider audience. Yet in order to accelerate progress, that wider audience is absolutely essential.

What are the effects of a large and energetic open development community on an industry? What happens when tens of thousands of people start making their products available for free, sharing data, designs, and improvements openly, and making money for services and expertise rather than through selling protected secrets? Fortunately we don't have speculate on this topic: we know. Look at the software industry, which is presently more vibrant and accomplished than it has ever been, whilst a large proportion of the most important software used around the world is open, freely shared, and constructed by a mix of professional and amateur contributors. Open source software is big business and that community gets things done.

Why is this relevant? It is relevant because what happens in software today will happen in biotechnology tomorrow. The tools and techniques of biotechnology continue to fall in price, and the knowledge of how to use them is already spread widely beyond the ivory towers in which it originated.

Transhumanism is in many ways the urge to self-improvement taken to its logical conclusion - that in addition to improving in ways that are presently possible, we should carry out the foundational work in technology that creates new ways for us to improve ourselves. So it all starts with simple, available tools to improve health, per this post at Sentient Developments: "there are a number of things we can do to extend our capacities and optimize our health in a way that's consistent with transhumanist ideals - even if it doesn't appear to be technologically sophisticated. While the effects of these interventions are admittedly low impact from a future-relativistic perspective, the quest for bodily and cognitive enhancement is part of the broader transhumanist aesthetic which places an emphasis on maximal performance, high quality of life, and longevity. ... Sure, part of being a transhumanist involves the bringing about of a radical future, including scientific research and cheerleading. But it's also a lifestyle choice; transhumanists actively strive to exceed their body's nascent capacities, or, at the very least, work to bring about its full potential. In addition to building a radical future, a transhumanist is someone who will, at any time in history, use the tools and techniques around them to maximize their biological well-being." Which is a slightly different take on the utilitarian considerations of keeping in shape so as to have the best chance of living into the era of rejuvenation biotechnology - with the pace of technology, a few years may matter. The decade or more of change you can exert on your life expectancy via lifestyle choices may make the difference between missing the boat or living a life of centuries. Or longer.

Link: http://www.sentientdevelopments.com/2011/06/primal-transhumanism.html

A good interview can be found at h+ Magazine, in which Aubrey de Grey and Ben Goertzel discuss a range of topics. Goertzel is an artificial intelligence researcher who strongly supports the goal of achieving radical life extension, so the interaction between the two fields is one of his interests:

Ben:

On a different note - I wonder how much do you think progress toward ending aging would be accelerated if we had an AGI system that was, let's say, roughly as generally intelligent as a great human scientist, but also had the capability to ingest the totality of biological datasets into its working memory and analyze them using a combination of human-like creative thought and statistical and machine learning algorithms? Do you think with this sort of mind working on the problem, we could reach the Methuselarity in 5 or 10 years? Or do you think we're held back by factors that this amazing (but not godlike) level of intelligence couldn't dramatically ameliorate?

Aubrey:

I think it's highly unlikely that such a system could solve aging that fast just by analysing existing knowledge really well; I think it would need to be able to do experiments, to find things out that nobody knows yet. For example, it's pretty clear that we will need much more effective somatic gene therapy than currently exists, and I think that will need a lot of trial and error. However, I'm all for development of such a system for this purpose: firstly I might be wrong about the above, and secondly, even if it only hastens the Methuselarity by a small amount, that's still a lot of lives saved.

My take on it is that the researchers working on strong artificial intelligence are stretching the point when they discuss the relevance of their work to rejuvenation research - but this is based on my own particular estimate of how the near future of of artificial intelligence development will likely play out. Any and all systems that help biologists manage information will do their part in accelerating progress towards interventions in aging - but the next two decades don't look likely to see much more than incremental advances in expert systems. Better expert systems and knowledge management tools are a good thing, but they aren't strong AI.

I think that the first strong AI will most likely emerge from emulation and simulation of the human brain, and the computing hardware powerful enough to enable that to happen will only just be emerging twenty years from today. Meanwhile, those twenty years between now and 2030 are a vitally important time for longevity science: either we get our act together and build (a) a meaningful, funded, supported research community and (b) the scientific basis for all the necessary biological repair technologies in that time frame, or rejuvenation biotechnology will not arrive in time for those of us heading into middle age today.

So for us, I don't see that strong AI development has an enormous relevance to the future of human longevity - no more so than any line of development likely to spin off incrementally better knowledge management tools. For our descendants, strong AI will absolutely reshape the world. But we're in a far worse position than they will be when it comes to time to wait and the tools at hand - not a hopeless position, but one that requires a great deal more work right here and right now.

We are advancing toward a new era of increasing powerful and sophisticated medical technology. The American Academy of Longevity is a non-profit 510(c)(3) IRS approved organization of physicians, scientists, health providers, medical researchers and individuals among the general public who are interested in and dedicated to promoting advances in the field of antiaging and longevity medicine. The members of the Academy believe that aging, death disability from cardiovascular disease, strokes, cancer, diabetes, neurodegenerative disorders of the brain are not inevitable. We believe that modern medical technology can retard, suspend and reverse biological aging.

The academy sponsors research and seminars to facilitate advances in the area of longevity and anti-aging medicine which include total hormone balancing therapy, diagnostics of preventable diseases and gene therapy. The academy focuses on education and clinically based research so that multiple benefits of these lifesaving and life-extending technologies can be more readily available to the public. The academy sponsors seminars to physicians and lay persons on how to reduce the risk of age-related degenerative diseases including exercise, diet and changes in their lifestyle to slow and reverse aging. These seminars also provide information on nutritional and vitamin/antioxidant therapies toward the same goal. The academy also promotes changes in medical school and residency curriculums so that future physicians will be well informed and educated in this area of medicine.

The academy defines aging as a disease because like a disease it is a process that ultimately leads to death.

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I noticed a recent open access paper (in PDF format) that explains in a very readable fashion how the last few years of new research into mitochondria may imply changes for a few important details in the mitochondrial free radical theory of aging.

Mitochondria are organelles of eukaryotic cells that contain their own genetic material and evolved from prokaryotic ancestors some 2 billion years ago. They are the main source of the cell's energy supply and are involved in such important processes as apoptosis, mitochondrial diseases, and aging. During recent years it also became apparent that mitochondria display a complex dynamical behavior of fission and fusion, the function of which is as yet unknown. In this paper we develop a concise theory that explains why fusion and fission have evolved, how these processes are related to the accumulation of mitochondrial mutants during aging.

If you look back in the Fight Aging! archives, you'll find a layman's explanation of how degenerative aging is caused in part by accumulating mitochondrial mutations. Mitochondria go bad as a natural consequence of their operation, and if enough go bad in the right way, and manage to escape the natural recycling mechanisms of the cell, then they take over that cell - causing it to malfunction, damage its surroundings, and release harmful reactive molecules that are carried throughout the body. Given enough cells doing this, you will become frail and eventually die as vital systems in your body become too damaged to operate correctly.

In this, we're all in the same boat. The interesting part of this process is that mitochondria swarm around a cell in bacteria-like herds, but the real damage only starts after a cell is completely taken over by clones of one particular mutant form of mitochondrion - a different dysfunctional clone army for each dysfunctional cell, each based on a particular random set of mutations. The question all along has been how that clonal takeover happens, and here the researchers propose that fusion is the culprit:

Another important finding of recent years is that individual mitochondria do not exist as permanently distinct entities, as has long been believed, but instead form a dynamic network within which the mitochondria regularly exchange proteins, [mitochondrial] DNA, and lipids by rapid fusion and fission processes ... The fact that mitochondrial fusions do occur revives an earlier idea that the selection advantage of deletion mutants is their reduced size, which allows them to replicate faster ... we propose that mitochondrial fusion is the underlying mechanism that opens the door for the clonal expansion of mitochondrial deletion mutants.

Does this view, if accurate, change any of the existing approaches to dealing with mitochondrial mutation and its considerable consequences to our health and life span? Not really, though one might argue that it complicates the question of what actually happens under the hood during the delivery of new, undamaged DNA into a cell's mitochondria. The problem remains the damaged DNA, and the resulting absence of necessary protein cogs in the mitochondrial machinery of energy generation and other functions - so either deliver fixed DNA, or deliver the needed proteins, and the problem is solved.

A review paper notes a number of lines of research aimed at introducing new DNA into mitochondria or new mitochondria into cells. Although discussed in the context of introducing specific types of damage to study, the much more important prospect is for repairing mitochondria - and thus the possibility of removing the significant contribution to aging caused by damaged mitochondria: "Maintenance of the mitochondrial genome is a major challenge for cells, particularly as they begin to age. Although it is established that organelles possess regular DNA repair pathways, many aspects of these complex processes and of their regulation remain to be investigated. Mitochondrial transfection of isolated organelles and in whole cells with customized DNA synthesized to contain defined lesions has wide prospects for deciphering repair mechanisms in a physiological context. We document here the strategies currently developed to transfer DNA of interest into mitochondria. Methodologies with isolated mitochondria claim to exploit the protein import pathway or the natural competence of the organelles, to permeate the membranes or to use conjugal transfer from bacteria. Besides biolistics, which remains restricted to yeast and Chlamydomonas reinhardtii, nanocarriers or fusion proteins have been explored as methods to target custom DNA into mitochondria in intact cells. In further approaches, whole mitochondria have been transferred into recipient cells. Repair failure or error-prone repair leads to mutations which potentially could be rescued by allotopic expression of proteins. The relevance of the different approaches for the analysis of mitochondrial DNA repair mechanisms and of aging is discussed."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21645537