LONGEVITY MEME NEWSLETTER
October 20 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.
- The Benefits of Induced Pluripotency
- Mitochondria, Aging, and Regulation of Research
- 4th SENS Conference Set For September 2009
- Latest Healthy Life Extension Headlines
THE BENEFITS OF INDUCED PLURIPOTENCY
When looking at the long term for biotechnology, it seems plausible that the most important outcome resulting from stem cell research (regenerative medicine, tissue engineering, and so forth) will not be cell transplant or replacement therapies. These cell therapies will make an enormous difference to the treatment of degenerative disease and the damage of aging over the next two decades, but of greater import is the ability to precisely manipulate and control our cells. To that end, the more laboratories working at the cutting edge of stem cell research the better, which is why I think that the discovery of induced pluripotent stem cells (iPS cells) is a big step forward - much bigger than its immediate and obvious applications:
"As I've noted in the past, it's essential to keep an eye on progress in infrastructure in science and research. When costs are lowered and easy of use increases, more people join the research community, and those already there achieve existing goals more rapidly. New goals, previously too costly to consider, become attainable. Cost of infrastructure is the foundation upon which a research community takes form and makes progress.
"Many more laboratories are equipped and ready to work with iPS cells than with embryonic stem cells ... In all, 812 labs in dozens of countries have requested the materials needed to reprogram ordinary cells into iPS cells, said Addgene, a Massachusetts-based repository for research supplies. By contrast, a half-dozen or so labs started working with embryonic stem cells in the months after his landmark 1998 paper, Thomson said."
Here is an example of the sort of progress that happens very rapidly in this environment:
"Now, a team of researchers led by Juan Carlos Izpisua Belmonte at the Salk Institute for Biological Studies, succeeded in boosting the reprogramming efficiency more than 100fold, while cutting the time it takes in half. In fact, they repeatedly generated iPS cells from the tiny number of keratinocytes attached to a single hair plucked from a human scalp."
MITOCHONDRIA, AGING, AND REGULATION OF RESEARCH
Some thoughts on the hole we find ourselves in:
"The dysfunctional regulatory regime for medical research in most developed nations ensures that significant funding is only available for applications of science to named diseases. Much of the limited groundwork presently taking place to develop a way to repair mitochondrial DNA is actually aimed at specific gene defects associated with specific forms of hereditary blindness, for example. This is the perverse result of the incentives in place: potentially revolutionary science is corralled and herded down alleys of limited application. No developer will invest in a revolution when the government prevents them from selling the results of their labor - and for every example you hear about, a hundred take place in silence. The real cost is what you don't see - researchers working towards what is possible rather than what is permitted."
Unlike the reversal of aging itself, where the scientific path forward to therapies is as clear and obvious as research ever can be, it's hard to see an easy way out of the present harmful status quo in regulation:
4th SENS CONFERENCE SET FOR SEPTEMBER 2009
Mark your calendars:
"The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Mprize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair -- reverse -- those changes, rather than merely to slow down their further accumulation."
The highlights and headlines from the past week follow below.
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LATEST HEALTHY LIFE EXTENSION HEADLINES
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/
On Aging and Myelin (October 17 2008)
Researchers have found an intriguing association: they "compared how quickly a group of males ranging in age from 23 to 80 could perform a motor task and then correlated their performances to their brains' myelin integrity. The researchers found a striking correlation between the speed of the task and the integrity of myelination over the range of ages. Put another way, after middle age, we start to lose the battle to repair the myelin in our brain, and our motor and cognitive functions begin a long, slow downhill slide. ... speed of a movement increases with the frequency of neuronal action potential (AP) bursts in the brain ... Fast movements require high-frequency AP bursts that depend on excellent myelin integrity over the entire axon network involved in controlling that movement ... the research suggests that the myelin breakdown process should also reduce all other brain functions for which performance speed is dependent on higher AP frequencies, including memory; it also supports the suggestion that myelin breakdown is a biological process of aging underlying the erosion of physical skills and cognitive decline." The question now becomes "why exactly does this decline in myelin happen, and what can be done to reverse it?"
Aubrey de Grey in H+ Magazine (October 17 2008)
The first issue of the transhumanist H+ magazine includes piece on radical life extension by Michael Anissimov and an interview with biomedical gerontologist Aubrey de Grey: "The three hardest aspects of SENS (at present - this could of course change!) are: the relocation of mitochondrial DNA to the nucleus to make mutations in the original mitochondrial DNA harmless; the introduction of microbial (or other foreign) enzymes into our cells to destroy molecules that accumulate in them; and the elimination of our cells' ability to prevent the ends of the chromosomes from shortening with each cell division, combined with stem cell therapies to address the side effects that this will cause. Research is proceeding healthily in all these areas, largely funded by the Methuselah Foundation. ... I'm actually not mainly driven by a desire to live a long time ... what drives me is to put myself (with luck) and others (lots and lots of others) in a position to make that choice, rather than having the choice progressively ripped away from me or them by declining health. Whether the choice to live longer is actually made is not the point for me."
Mechanisms of Cancer Versus Aging (October 16 2008)
Researchers continue to uncover the mechanisms underlying the balance between aging and cancer. Many aspects of our biology have evolved to shut down as damage accumulates, suppressing cancer but causing loss of function: "Four genes that suppress tumor formation also regulate the ability of adult stem cells to replace worn-out tissues, as well as the shutdown of stem cells during aging. The genes switch on and off in a coordinated fashion as cells age to reduce the risk of cancer. In the process, they also shut down stem-cell function in aging tissues, reducing their capacity to regenerate. ... The four genes examined in the study were Ink4a, Arf, Hmga2 and let-7b. ... Ink4a, well known for its role as a tumor suppressor, becomes increasingly active with age and shuts down stem-cell replication in older mice. Flicking that genetic switch likely serves as a defense against cancer-causing genetic mutations, which accumulate as cells repeatedly divide. ... Ink4a's activity in mouse neural stem cells is regulated by Hmga2, which in turn is controlled by let-7b. The same relationship is likely at work in humans, who possess the same four genes."
Gene Therapy Versus Retinal Degeneration (October 16 2008)
Via EurekAlert: "Researchers have used gene therapy to restore useful vision to mice with degeneration of the light-sensing retinal rods and cones, a common cause of human blindness. ... This is a proof of principle that someday we may be able to repair blindness in people with conditions like retinitis pigmentosa and macular degeneration. There are several limitations we need to overcome before we can begin clinical trials, but I'm optimistic that this work may someday make a big difference for people who otherwise would have no vision at all. ... The study was designed to investigate the effect of expressing the light-sensitive protein melanopsin in retinal ganglion cells. These specialized neurons receive light signals from the rods and cones and carry those signals into the brain via the optic nerve, which is formed from the cells' axons. Melanopsin is usually produced in a subset of cells that are involved with establishing circadian rhythms but not with vision. The [researchers] used the standard viral vector adeno-associated virus to deliver the gene encoding melanopsin throughout the retinas of mice whose rod and cone photoreceptors had degenerated from lack of a crucial protein."
Sirtuins Increased By Human Calorie Restriction (October 15 2008)
Here's a study confirming that sirtuins are indeed overexpressed during the practice of calorie restriction in humans. That should please the resveratrol brigade: "Sirtuins may provide novel targets for treating some diseases associated with oxidative stress, such as obesity and its comorbidities. However, there are a few in vivo studies in humans about the potential role of sirtuins as therapeutic targets among obese patients undergoing caloric restriction. ... Gene expression of two sirtuins (SIRT1 and SIRT2) [of] obese subjects [before] and following an 8-week hypocaloric diet was investigated. ... The intervention up-regulated the expression of both sirtuins ... SIRT1 and SIRT2 may serve as key regulators for some obesity comorbidities related to antioxidant status." The more interesting question is whether these effects occur for people of a more reasonable weight range.
More Cell Transfer Immunotherapy (October 15 2008)
A strategy analogous to early stage stem cell therapies is showing promise for immunotherapy. From the Telegraph: "Cancer patients could have immune cells removed and cultivated in piglets before being injected back into them to boost the body's natural defences ... The new stem cells, which would then be implanted back into the patient, could even be modified in the piglet so as to boost their disease fighting powers, experts believe. They said the new system could mark a major breakthrough in the process which is known as cell transfer immunotherapy or T-cell treatment. ... Immunotherapy is thought to work because usually there are too few of the cells naturally in a patient's body to fight cancer effectively but by boosting them, it boosts natural defences. In its most successful use to date one American patient suffering from advanced skin cancer even made a full recovery following the treatment. This was even though the disease had already spread to the lymph nodes and lungs." The use of pigs solves a problem of cost: culturing immune cells is still very challenging, and thus expensive and even impossible for some patients.
Thoughts on Tissue Engineering (October 14 2008)
From the Tartan: "As for regrowing whole limbs, Badylak is unsure of when technology will be advanced enough for such a feat. 'That's an impossible question really to answer. I do think that we will be able to stimulate the regrowth of at least digits. The only way we will be able to do that is by understanding the signaling mechanisms that occur in the fetus, when these sorts of structures are normally developed. In a fetus if you amputate these structures at an early enough stage, the fetus will regrow a limb. Yet we lose that ability as we develop into a newborn.' The hardest obstacle of regenerative medicine lies within the cellular communication system. Badylak explained that to regrow a tissue, the cell requires the right kind of signal to start, so that it can in turn stimulate the right cells. The biggest challenge is finding the master switch, a molecular signal which will tell the injured tissue to respond with the means to regrow instead of just heal, and afterward, finding out how activate it. These switches are genes that need to be activated. When activated, the genes can then express proteins that can trigger a cell regeneration cascade."
Hourglass IV Blog Carnival on Aging Science (October 14 2008)
Houseglass IV is over at Existence is Wonderful: "In putting together this Carnival, something never far from my mind was the notion of that point at which something ceases to be considered monstrous or strange and is assimilated into the realm of the ordinary, or acceptable, or even welcome. I can only imagine how odd and disturbing the idea of transplanting organs must have seemed prior to it actually being done -- and yet nowadays, if you tell someone you're planning on donating a kidney to your sick cousin, you're likely to be told, 'Oh, how nice!' as opposed to, 'Ugh! What is wrong with you?' ... Similarly, speculations about impressive longevity gains or other boundary-pushing advances seem to intrigue some while frightening others -- which is understandable considering that nobody knows what is ultimately going to be possible when it comes to altering, maintaining, and fine-tuning bodies over time, nor what the implications of any of this will be."
Looking at BioTime (October 13 2008)
From Depressed Metabolism: "Unless you are a long-time cryonicist or a surgeon, you may not have heard of BioTime before. This company, recently profiled for its innovative stem cell research in Life Extension Magazine, is best known for producing the blood-volume expander Hextend, which was initially developed by Trans Time, an early cryonics company performing ultra-profound hypothermia research. ... things are changing at BioTime. Under the direction of CEO Dr. Michael West, and capitalizing on the highly successful sales of Hextend and related products, the company is now heading in a new direction: regenerative medicine. ... Dr. West's mission [is] to understand how to make somatic (i.e., body) cells immortal and then apply this technology to the treatment of aging and aging-related diseases. BioTime is now driven by the potential for stem cell therapy to repair and regenerate organs and tissues and, if possible, to radically extend human lives."
On Replacement Parts (October 13 2008)
Existence is Wonderful looks at the prospects for replacement organs - while we wait for therapies capable of reversing the biochemical damage that makes it necessary to replace organs: "What is needed next, along with wider recognition of the lack of an expiration date on an individual person's value, is a means to replace worn-out parts that doesn't require nearly so many dead donors, and that doesn't pose so much danger to the recipient in terms of infection and immune issues. ... Bioartificial parts are essentially the products of the emerging science of tissue engineering ... applications of tissue engineering will benefit people of all ages (bioengineered bladders have already been successfully implanted in several children), but the growing elderly population stands to benefit tremendously from anything that makes effective replacement parts safer and more readily available. Bioartificial parts could potentially take innumerable forms, but given the organs people really depend most on for [survival], it is definitely good to see that laboratory results (and in some cases, clinical/experimental trials) have been obtained for bioartificial arteries, hearts, livers, and kidneys."