Longevity Meme Newsletter, February 19 2007

February 19 2007

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.



- How Far Can We Go With Enhanced Regeneration Alone?
- Discussion
- Latest Healthy Life Extension Headlines


If we restrict ourselves to the fruits of regenerative medicine over the years to come, just how much additional healthy life can we obtain? What are the bounds of the possible? Do we need more than just regenerative medicine, or is it enough to move us all the way to greatly extended healthy life spans? Researcher and blogger Attila Chordash and I exchanged views on the topic this past week:


"Hypothetically, yes, pretty much everything except your brain is open to replacement just as soon as scientists can figure out how to build and install those replacements in a useful manner. That's a high bar, however. Your body isn't easily divided into piecemeal components; it's an overlapping bundle of interlinked, complex components - age-related damage to one system may make many related replacements useless or even counterproductive. Developing the technology base for safe replacement of the entire aging body is a long-term project - not impossible, but certainly not something that you'll be seeing any time soon.

"Your great-grandchildren may well live in a world in which bodies are like cars: built well, and discarded with regret when they have passed their prime, exchanged for new models. If we are to live to see that world, however, we have to take smaller first steps in the fight to defeat aging. The stem cell technologies of the next few decades are but one part of the technology base needed to repair the aging human body and brain."


"Systemic regenerative medicine is a coherent and inclusive engineering approach to eliminate all aging related problems indefinitely. Definition: Systemic regenerative medicine theoretically means the continuous, gradual and consecutive regeneration of every tissue and organ of the human body n times by combined regenerative medicine approaches, i.e. tissue engineering (in vitro grown organs and tissues implants or parts of them), systemic (via circulation) and locally targeted stem and progenitor cell transplantation, and endogenous stem cell niche activation with proper growth factor delivery aiming to maintain the physiological turnover and condition of the human body."


"Which may be the case, and you never know for sure until the job is either done or failed. It seems to me I have the more defensible position, if somewhat less clearly articulated - but I'd be happy to proven wrong on this topic, given that the field of regenerative medicine is well on the way to become a behemoth to dwarf the cancer research community. No need for the years-long process of building up understanding, support, funding, institutes and enthusiasm - all those early days are behind us for regenerative medicine, tissue engineering and similar areas of research. Great and rapid progress lies ahead.

"But, inconveniently, regeneration is not rejuvenation. Salamanders still grow old and die, as do the impressive mice of Ellen Heber-Katz. What Chordash is discussing is much more than assisted healing processes culled from the natural world, of course - it's more like the replacement scenario I touched upon a few days ago. Chordash sees this arriving sooner than I would predict."


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!


Founder, Longevity Meme



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/

Early Days of Artificial Eyes (February 18 2007)
In the years ahead, fully functional artificial eyes will be an option for the blind. Science Daily notes that the path to that end is just getting underway today - a little healthy competition for the methods of regenerative medicine: "The first phase of our implant work began in 2002. We have successfully implanted six patients in the trial, and we have found that the devices are indeed electrically conducting and can be used by patients to detect light or even to distinguish between objects such as a cup or plate. ... While the first generation of implants contained 16 electrodes laid out on an array, the Argus II is designed with 60 electrodes, which is intended to allow for higher-resolution images. The new device is also approximately one quarter the size of the original, reducing surgery and recovery times. The array is attached to the retina and used in conjunction with an external camera and video processing system to provide a rudimentary form of sight to implanted subjects." The capabilities of exactly these sorts of technologies have improved by something like a factor of 1000 in the past 15 years - the field of endeavor concerned with integrating devices into the human body will catch up with that trend.

More On Artificial Cells as Medical Tools (February 18 2007)
From earlier this month, a Nanowerk article goes into more detail on the proposed use of artificial cells and cell-like structures as medical devices: "Some fundamental problems like the targeting of nanoparticles in vivo, the transport of unstable drugs, and the dosage control of drug-carrying nanoparticles lead some scientists to think even one step further. Rather than delivering external drugs into the body, they conceptualize 'pseudo-cell' nanofactories that work with raw ingredients already in the body to manufacture the proper amount of drug in-situ under the control of a molecular biosensor. ... This approach draws its inspiration from the ability of the human body to self-medicate by actively adapting molecular production in response to its intrinsic biochemistry. This new approach proposes that molecular machinery could, in principle, be introduced into the body to convert pre-existing materials into therapeutic compounds, or to change molecules that a patient is unable to process, owing to some medical condition, into other compounds that the body can process. ... rather than reverse engineering an extremely complex system, generating an artificial cell provides a robust platform where researchers can add functionality in a component-by-component process. Furthermore, artificial approaches may be more controllable as living cells can respond in unanticipated ways."

T Cell Biochemistry and Immune System Aging (February 17 2007)
From Ouroboros, a look at research into internal changes in T cells with aging, some the mechanisms driving the ongoing depletion of the naive T cell population, some not: "The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein-Barr virus infection, this critical process can become dysregulated and responding T-cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T-cells is a poor prognostic factor for survival in the very elderly. ... These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention. ... A possible mechanism for some age-related transcriptional changes is provided by Das et al., who describe the negative effect of oxidation (both experimental and age-related) on the proteasome. ... These results suggest that the decrease in proteasomal activities observed during aging may be secondary to oxidative stress and underlie immune senescence."

There Are No Deaf Chickens: How Does This Help? (February 17 2007)
EurekAlert! takes a look at one group working towards regenerative cures for deafness: "Heller's vision is to develop a variety of possible cures for deafness. For the past year and a half [he's] been focused on two paths: drug therapy - which could be as simple as an application of ear drops - and stem cell transplantation into the inner ear to remedy hearing loss. Currently he's working on perfecting the steps toward eventual stem cell transplantation into humans, with the goal of first curing deafness in mice within the next five years. His lab is also busy studying the ability of birds to regenerate the tiny hair cells in the cochlea. It's these cells that convert the mechanical energy of sound into electrical impulses that are sent to the brain so that a chicken, a mouse or a human can hear. Chickens, like all birds, have the ability to spontaneously regenerate these hair cells, which explains why there are no deaf birds. This is promising because it means the genetic program for regeneration exists somewhere in the vertebrate family. We know there is an unknown signal to regenerate that we could use, but we first have to find it."

Testing the Bounds of Regeneration (February 16 2007)
(From Delaware Online). Researchers continue to explore the boundaries of regeneration: how much or how little will we have to do to convince human biochemistry to regrow digits and limbs? "It sliced off his fingertip, leaving just a bit of the nail bed. The missing piece, three-eighths of an inch long, was never found. ... Spievack, however, did have a major advantage - a brother, Alan, a former Harvard surgeon who'd founded a company called ACell Inc., that makes an extract of pig bladder for promoting healing and tissue regeneration. ... Within four weeks his finger had regained its original length, he says, and in four months 'it looked like my normal finger.' ... it's not completely clear what happened inside Lee Spievack's finger. The broad outline is pretty straightforward. The powder is mostly collagen and a variety of substances, without any pig cells ... It forms microscopic scaffolding for incoming human cells to occupy, and it emits chemical signals to encourage those cells to regenerate tissue ... we are very uninformed about how all of this works. There's a lot more that we don't know than we do know." This is one end of a broad spectrum of work presently taking place - interesting results will come in the years ahead.

CIRM Awards $45M in Grants (February 16 2007)
For those keeping track of such things, SFGate.com notes that first major set of grants have been rolled out by the California Institute for Regenerative Medicine (CIRM): "Officials for [CIRM] authorized a modest package of 72 grants totaling $45 million over the next two years. Researchers at 20 institutions, most of them affiliated with the University of California, will carry out the research in labs throughout the state. ... Most of the first research projects announced today involve discovering the fundamental properties of stem cells derived from early-stage human embryos. ... Scientists want to find better ways to isolate the flexible stem cells from the embryos so they can be turned into any of the myriad cell types that comprise the human body, particularly those that fall prey to disease such as diabetes and neurodegenerative disorders." The press release at the CIRM website lists the specific projects funded in this set of grants; quite a few attempts to better control cellular differentiation are amongst their number.

Li-Fraumeni Syndrome: p53, Telomeres and Cancer (February 15 2007)
Medical researchers are learning a great deal about the age-related degeneration of human biochemistry by looking at the extreme edge cases and malfunctions - such as Li-Fraumeni syndrome in the case of increased cancer risk with advancing age: "Li-Fraumeni was associated with inheritance of a mutated form of the p53 tumor suppressor gene, but we also noticed each generation developed cancer earlier than the preceding generation ... we have discovered that telomeres become shorter in each generation of disease carriers, leading to a genetic instability that primes them for progressively earlier cancers ... Telomeres are repeated sequences of DNA at the tips of every chromosome that function as a sort of genetic slack. As cells grow and divide throughout life, the chromosomes, which contain all of an individual's genetic information, replicate as well. The enzymes that create copies of chromosomes cannot, however, physically reach the very end of the chromosome, so they leave a minute bit of this telomere slack behind each time. This is known to researchers as the 'end replication problem' and has made telomeres an important subject of research in the science of aging and cancer." What then is the mechanism linking p53 and telomere length?

Ingenuity in Bioengineering (February 15 2007)
Via EurekAlert! a good example of the sort of combinatorial ingenuity - so common in the cancer research community these days - enabled by modern biotechnology: "HIV knows how to insert itself into many different types of cells. A portion of the HIV protein called TAT can transport biologically active compounds into cells. TAT is small, but it can move massive molecules. You could almost hook TAT up to a train, and TAT would drag it inside a cell. So we've taken advantage of this ability ... the researchers describe using TAT to pull a protein called Bim into cancer cells. TAT alone cannot cause AIDS and has no adverse health effects. Bim acts as a tumor suppressor and causes cancer cells to die through apoptosis ... Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die. ... clinical trials of these compounds could be just a few years away." The components of cures and transformative biotechnologies already exist, scattered a piece here and a piece there, waiting for clever humans to learn how to use them to create more healthy life for the ill and aging.

Ouroboros on Reversing AGE Accumulation (February 14 2007)
You'll find more commentary on recent research into advanced glycation endproducts (AGEs) and alagebrium over at Ouroboros: "A drug was designed against a specific form of age-related damage, demonstrated to attack this damage in vitro, and then shown to be efficacious in a clinical setting. In addition to providing good news for sufferers of hypertension, the study takes an important step toward verifying the model that AGE in fact do play a causative role in the onset of age-related disease. Most enticing is the idea that AGE reversal (in this case via treatment with alagebrium) appears not to delay the onset of of damage but to actually reverse it - even in elderly patients, even after that damage has contributed to a potentially life-threatening clinical condition. Slowing the accumulation of damage will be an important part of the anti-aging pharmacopoeia of the future - an ounce of prevention being worth a pound of cure - but unless the rate of damage accumulation can be slowed to zero, methods of reversing existing damage will also be required."

On the Importance of Framing (February 14 2007)
Anne C. looks at how to frame persuasive advocacy for healthy life extension research: "Matt thinks that maybe we ought to start simple -- e.g., unless specifically grilled on the end-goals of longevity research, we should simply attempt to frame it as a natural extension of medical care. The purpose of medicine, after all, is to save lives, so longevity medicine really ought to be a no-brainer. The only reason it isn't for a lot of people might be due to the way it can sometimes end up being framed, so framing it properly is undeniably important. This is a subtle point, but possibly one worth mulling over. I have become reasonably convinced that focusing too heavily on specific diseases in terms of research could be harmful -- that is, it might encourage progress in a direction that results in treatments that really only apply to people who are already experiencing dangerous or even deadly symptoms." I'm in favor of advocacy to push out the bounds of the debate, and against any sort of retreat to moderation for the sake of short term advantage - but others are trying the moderate path (or at least what is now the new moderate path, given that the limits of the discussion have been extended). May the best efforts win.

Cloning From Adult Stem Cells (February 13 2007)
Via ScienceDaily, a research group is claiming greater success than in past years in cloning efforts using adult stem cells: "A main hurdle in nuclear transfer with adult cells has been its efficiency - out of a hundred attempts, only a handful may succeed - with reported success rates never reaching into double digits. ... Using purified adult skin stem cells as our source of nuclei, we have found that higher nuclear transfer efficiencies can be achieved. ... Nuclear transfer can also be used to make embryonic stem cell lines, a process which can be done in a tissue culture dish and which is simpler and more efficient than generating a cloned mouse. Although this procedure has not yet successfully generated human embryonic stem cell lines, once technological hurdles are overcome, it may be possible in the future to use a patient's skin stem cells to tailor make embryonic stem cell lines, circumventing the problem of immune rejection." An early step in the path to growing replacement tissue (and eventually organs) to order from your own cells, in other words. It's a way to go yet to supercharge regenerative medicine with this line of work - and if you work from adult cells, you transfer some of the damage that comes with being older - but this is a positive step forward.

Results From the LysoSENS Soil Contest (February 13 2007)
From the Methuselah Foundation: researcher John Schloendorn "requested soil donations throughout 2006, in order to discover microbes that degrade 'junk' molecules inside our bodies - the LysoSENS project, aimed at repairing one type of age-related damage via bioremediation. Further encouragement for the donors was provided by a soil contest - $100 for what the investigators deem the "best" submitted samples, i.e. the ones that contained the most biodiversity, and were the most difficult to collect. We were amazed at the level of creativity and organizational talent that our soil donors threw at this problem. We are proud to announce the winners of the contest and their stories. ... Michael obtained the cooperation of several Kentucky funeral directors. This resulted in a large selection of deep grave samples from different graveyards. We used these to construct our first large (>3 Gbp) metagenomic clone library, which has not yet undergone selection. This experiment will hopefully provide an answer to the question of whether graveyard soil is the preferred sample source, as a microbial habitat where our target compounds naturally get degraded. Mike would like to acknowledge the funeral directors Mr. Bernard, Mr. Wilson, and Mr. Hamm."

The Anti-Aging Cargo Cult (February 12 2007)
As you're reading this Guardian piece, remember that for every huckster so obvious that you'd never fall for their nonsense, there are a dozen who are much better at their nefarious trade - it pays to take a closer look at everyone who is trying to sell you something. "She says DNA is an anti-ageing constituent: if you 'do not have enough RNA/DNA', in fact, you 'may ultimately age prematurely'. Stress can deplete your DNA, but algae will increase it: and she reckons it's only present in growing cells ... the scholarliness of her work is a thing to behold: she produces lengthy documents that have an air of 'referenciness', with nice little superscript numbers, which talk about trials, and studies, and research, and papers ... but when you follow the numbers, and check the references, it's shocking how often they aren't what she claimed them to be in the main body of the text. McKeith's pseudo-academic work is like the rituals of the cargo cult: the form is superficially right, the superscript numbers are there, the technical words are scattered about, she talks about research and trials and findings, but the substance is lacking. I actually don't find this bit very funny. It makes me quite depressed to think about her, sitting up, perhaps alone, studiously and earnestly typing this stuff out."

"Win Longevity For All" (February 12 2007)
From the Institute for Ethics and Emerging Technologies: "When seniors stay healthy and vigorous they can continue contributing their lifetime of accumulated skill and experience to society, without driving up nursing or healthcare costs, or becoming dependent on loved ones. If medical therapies could be developed which slowed the rate of aging, and the development of disease and disability, we may be able to slip past the demographic transition in economic strength, and greater health and longevity for everyone. This is the promise and challenge of the 'Longevity Dividend.' Join us in Chicago on July 23rd for a day long seminar with leading experts on the politics, science and political economy of longevity - including Jay Olshansky and Aubrey de Grey - to help build the campaign for an intensive international research program on anti-aging medicine. ... The seminar will take place the day before the three-day gala Transvision 2007, with keynoter Ray Kurzweil. ... The targets for this event are: scholars and journalists interested in the future of aging and healthcare; legislative aides and policy makers considering the Longevity Dividend as a policy program; pro-longevity, health care and senior activists interested in building the Longevity Dividend campaign."



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