Fight Aging! Newsletter, March 14th 2011

March 14th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!



- Aubrey de Grey at the iLabs Singularity Summit
- You Can't Eat Your Way to Radical Life Extension
- The Short End of the Gender Stick
- Naked Mole Rats and Their Lack of Cancer
- Discussion
- Latest Headlines from Fight Aging!


An interviewer caught up with biomedical gerontologist Aubrey de Grey of the SENS Foundation at a recent event in Milan. Video can be found in the Fight Aging! post linked below:

"I caught up with Aubrey de Grey at the iLabs Singularity Summit in Milan, Italy on March 5. In this video he talks about the progress SENS made in securing funding sources, the latest scientific results, and the need to further its perception as a sound research program all over the world."


Far too much time is spent focusing on what people stick into their mouths, and a great many folk hold fantastical, unscientific beliefs about what can be achieved through diet alone:

"The simple, unfortunate truth of the matter is this: if eating exceedingly well really could let people live to 100 and beyond with any reliability, then this would be well known, and the world population would include thousands upon thousands upon thousands of centenarians. But people who do the very best largely die far earlier than that - few of them make it into their 80s, let alone 90s. Living well has great worth: clearly there is much that can be done to optimize your own person life expectancy under present day medical technology. But don't expect to live to 100 under those conditions, because the odds are that you won't. The only thing that will bring much longer life to all of us is the advance of medical technologies into the realm of repairing the biological damage of aging."


In comparison to women, men don't do so well when it comes to mortality rates and life expectancy, having shorter lives and a greater risk of death in every age group:

"The disparity between male and female life expectancy is well known and widely studied, but not definitively understood. What this means in practice is that there exists a very wide range of theories to explain some or all of the gender longevity gap. ... On the one hand it is fascinating that we stand upon the verge of being able to repair aging, yet at the same time we cannot answer what appears to be a simple question about the nature of aging. On the other hand, this is an apt illustration that sometimes what appear to be simple questions are in fact very complex questions. In this case, the answer to why men and women exhibit different mortality rates and life expectancies must involve the summed interactions of all the systems of human biology, subject to the statistical blurring of a million different lifestyles lived concurrently by billions of people."


Fight Aging! here revisits cancer-free naked mole rats, a species in which individuals live nine times longer than the members of similarly sized rodent species:

"No naked mole rat has been observed to suffer from cancer, a fact that is attracting interest from the cancer research community as this species becomes more widely studied. If the biochemistry that leads to this feat can be understood, it is possible there exists an economical way to port that cancer immunity to humans."


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!



Friday, March 11, 2011
Neurodegeneration has an inflammatory component, and some research groups use that as a starting point for treatment: "Neurodegenerative diseases like Alzheimer's and Parkinson's are partly attributable to brain inflammation. Researchers [now] demonstrate [that] a well-known family of enzymes can prevent the inflammation and thus constitute a potential target for drugs. Research suggests that microglial cells - the nerve system's primary immune cells - play a critical part in neurodegenerative diseases, such as Alzheimer's and Parkinson's. The over-activation of these cells in the brain can cause inflammation, resulting in neuronal death. Scientists [have] now found a way to prevent the activation of the microglia and consequently the inflammation they cause. The key is the blocking of enzymes called caspases, which the team has shown control microglial activation. ... By studying cell cultures and mice, the researchers show that certain caspases (3, 7 and 8) activate rather than kill microglial cells, which triggers an inflammatory reaction. Mice given caspase inhibitors displayed fewer activated microglia and less inflammation and cell death in the surrounding neurons."

Friday, March 11, 2011
An example of a class of stem cell medicine that involves manipulation of existing populations of cells in the body: "Circulating through the bloodstream of every human being is a rare and powerful type of cell, one that can actually create new blood vessels to bypass blockages that cause heart attacks and peripheral artery disease. Though everyone has these cells - called endothelial progenitor cells - they are often dysfunctional in people prone to vascular disease. Now researchers [have] discovered that a molecule - called Wnt1 - can improve the function of endothelial progenitor cells, increasing the blood flow to organs that previously had been cut off from the circulation. The finding could enhance clinical trials already testing these powerful cells in patients hospitalized with cardiac arrest. ... A number of studies in the past few years have suggested that genes that play an important role during early development and get 'turned off' during adulthood may also get 'turned on' or expressed again in response to injury, such as heart attack. [Researchers] found that one gene in particular, Wnt1, was expressed during development of blood vessels, shut off during adulthood and then re-expressed in angiosarcoma, a cancer of endothelial cells. ... treating these special cells with Wnt1 not only greatly increased their function but also their number. Next, [researchers] investigated what effect the protein would have on a mouse model of peripheral artery disease, an illness in humans caused by decreased blood flow to the extremities. They found that treating these animals with a single injection of the Wnt1 protein resulted in almost three fold increase in blood flow in the affected areas."

Thursday, March 10, 2011
It is known that the hypoxic response at a cellular level is involved in the longevity induced by calorie restriction, and works like most forms of hormesis - by stimulating cells to greater housekeeping efforts. Here is an open access paper on the subject: "A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for the acquisition of a long life span by mutants with reduced respiration in C. elegans. We suggested that increased levels of reactive oxygen species (ROS) produced in the respiration mutants increase HIF-1 activity and lead to this longevity. In this research perspective, we discuss our findings and recent advances regarding the roles of ROS and HIF-1 in aging, focusing on the longevity caused by reduced respiration. ... Many interesting questions remain unanswered. Which tissues and functional target genes are important in the regulation of aging by HIF-1? How can both up-regulation and down-regulation of HIF-1 promote longevity? What is the molecular mechanism by which mitochondrial ROS stimulates HIF-1 activity? ... Since many aging-regulatory processes are conserved between C. elegans and mammals, these studies may also provide insights into the regulatory mechanisms of aging in mammals, including humans. Moreover, in addition to aging, HIF-1 and mitochondrial impairment have been implicated in various human diseases such as cancer, diabetes, and neurodegenerative diseases. Thus, we believe that these future studies will help us better understand the pathophysiology of these diseases."

Thursday, March 10, 2011
EurekAlert! passes on an advance in the technology of reprogramming cells: "In the past few months, a slew of papers have indicated that the therapeutic potential of a promising type of stem cell, called induced pluripotent stem (iPS) cells, might be limited by reprogramming errors and genomic instability. iPS cells are engineered by reprogramming fully differentiated adult cells, often skin cells, back to a primitive, embryonic-like state. Given these problems, a team of researchers [wondered] if there might be a better way to regenerate lost tissue to treat conditions like heart disease and stroke. ... they outline a method to obtain a new kind of stem cell they call 'induced conditional self-renewing progenitor (ICSP) cells.' ... It's amazingly cool that we can dial adult cells all the way back to embryonic-like stem cells, but there are a lot of issues that still need to be addressed before iPS cells can be used to treat patients. So we wondered... if we just want to treat a brain disease, do we really have to start with a skin cell, which has nothing to do with the brain, and push it all the way back to the point that it has potential to become anything? In this study, we developed ICSP cells using a cell from the organ we're already interested in - the nervous system, in this case - and pushed it back just enough so it continued to divide, giving us a quantity that we were able to apply efficiently, safely and effectively to treat stroke injury in a rodent model. ... the [reprogramming gene] used here is conditionally expressed. This means that ICSP cells can only produce [the gene] when the researchers add a compound called tetracycline to laboratory cultures. When tetracycline is removed, the cells cease dividing and start differentiating. Then, once transplanted into to an animal model, ICSP cells are no longer exposed to tetracycline and take their growth and differentiation cues from their new environment."

Wednesday, March 9, 2011
Another in a series of articles on this topic from Singularity Hub: "The blind in Europe have reason to rejoice, the world's most advanced artificial retina has just received the CE Mark, approved for use in new patients. The Argus II, developed by Lawrence Livermore National Laboratory and marketed by Second Sight, is on sale in the EU, but still awaiting FDA approval here in the US. Luckily, clinical trials are already underway and we could get the amazing device here soon. With the Argus II, blind patients use an external camera to pick up video that is wirelessly transmitted to an electrode array surgically implanted in the eye. While full vision is not restored, the 60+ electrodes allow for some distinction of outlines and other basic shapes. Definitely an improvement over blindness. ... a camera embedded in a pair of glasses records the world in front of the patient. A wearable computer takes that image and transforms it into a basic series of impulses. That pattern is transmitted to the Argus II implant which rests inside the eye, and which is attached to the back of the eye through an electrode array. ... Although software improvements may arrive first, hardware upgrades are also on the horizon. The Argus II operates with about 60 electrodes in its array. That's 60 points of data for your eye to interpret. The Argus III, currently under development at LLNL, should have 200+ electrodes. Perhaps considerably more. It will take a thousand or so to make out human faces accurately, but the Department of Energy is pushing LLNL towards that goal, and beyond. As slow as the progress in artificial retinas has been, it shows no sign of stopping. There are other projects outside of the Argus series, at least two (one in MIT, another in Germany) show serious promise, and even have superior qualities to the Argus in some respects. I have no doubt that we could, eventually, reach a resolution that equals that of the human eye. Perhaps, with a different kind of interface, we could even see in greater detail than nature intended."

Wednesday, March 9, 2011
Via ScienceDaily: "Even long after it is formed, a memory in rats can be enhanced or erased by increasing or decreasing the activity of a brain enzyme. ... Our study is the first to demonstrate that, in the context of a functioning brain in a behaving animal, a single molecule, PKMzeta, is both necessary and sufficient for maintaining long-term memory. ... Unlike other recently discovered approaches to memory enhancement, the PKMzeta mechanism appears to work any time. It is not dependent on exploiting time-limited windows when a memory becomes temporarily fragile and changeable - just after learning and upon retrieval - which may expire as a memory grows older. ... This pivotal mechanism could become a target for treatments to help manage debilitating emotional memories in anxiety disorders and for enhancing faltering memories in disorders of aging. ... In their earlier studies, [researchers] showed that even weeks after rats learned to associate a nauseating sensation with saccharin and shunned the sweet taste, their sweet tooth returned within a couple of hours after rats received a chemical that blocked the enzyme PKMzeta in the brain's outer mantle, or neocortex, where long-term memories are stored. In the new study, they paired genetic engineering with the same aversive learning model to both confirm the earlier studies and to demonstrate, by increasing PKMzeta, the opposite effect. They harnessed a virus to infect the neocortex with the PKMzeta gene, resulting in overexpression of the enzyme and memory enhancement. Conversely, introducing a mutant inactive form of the enzyme, that replaced the naturally occurring one, erased the memory - much as the chemical blocker did."

Tuesday, March 8, 2011
From CNN: "Engineering organs begins with something missing - a phantom organ in the body that causes a patient incredible discomfort, dysfunction or pain. It ends with a Star Trek-esque feat of engineering where missing organs are replaced using cells culled from a patient's own body. In a small pilot [study] scientists reported successfully reconstructing urethras in five young patients, using their own cells. ... We were able to create patients' own tissue that actually belongs there. If the tissue is supposed to be there, hopefully we will do better by the patient. ... Patients had their engineered urethras implanted between March 2004 and July 2007 at the Federico Gomez Children's Hospital in Mexico City. Their urethras continued to function after several years' follow-up. The urethra is a narrow tube that connects the bladder with the genitals, providing a conduit to usher waste out of the body. When it is damaged - sometimes congenitally, or as result of disease, pelvic fractures or other traumas - it is usually replaced using tissue harvested from the lining of a patient's cheeks or using skin grafted from another area of the body. ... Unfortunately for the narrow structures in the body (like urethras), they are kind of complex because they tend to collapse. Every organ has its own challenges. ... The challenge with traditional urethra replacement is creating a viable tube, one that will not easily collapse. And that is where engineering urethras may offer some benefit. The first step for engineering a new urethra is to take a very small piece of the patient's own tissue (around half the size of a postage stamp) from the bladder area. Cells are scraped from the biopsied tissue, allowed to multiply, after which muscle cells are separated from urethral cells. It is the next few steps in the process that sound like science fiction. When there are a sufficient number of cells, scientists 'seed' them - much like you would seed a new lawn - onto a mesh scaffold that is shaped like a urethra. The inside of the mesh is coated with urethral cells while the outside gets muscle cells. ... The seeded structure is placed in an incubator for about two weeks, in a 'cooking' process that [simulates] how cell growth occurs inside the body. After that, the newly engineered urethra is ready to be implanted into the patient."

Tuesday, March 8, 2011
The processes of cellular housekeeping appear to be important in aging, and here is an example of what can be achieved by selectively boosting their operation: "Gene therapy that boosts the ability of brain cells to gobble up toxic proteins prevents development of Alzheimer's disease in mice that are predestined to develop it ... the treatment - which is given just once - could potentially do the same in people at the beginning stages of the disease. ... giving brain cells extra parkin genes promotes efficient and effective removal of amyloid particles believed to be destroying the neurons from the inside. This revved up protein disposal process prevents the cells from dying and spewing amyloid proteins into the brain, where they stick together and clump into plaque. ... Many neurodegenerative diseases are characterized by a toxic build-up of one protein or another, and this approach is designed to prevent that process early-on. ... providing brain cells with about 50 percent more parkin protein activates two parallel garbage-removal processes within the brain. One is ubiquitination, in which errant proteins are targeted for destruction and recycling within the cell. The other process is autophagy, in which membranes form around damaged mitochondria (the cell's power plants) and these membranes fuse with lysosomes that destroys the contents. This is particularly important [because] damaged mitochondria have been found to clog the insides of neurons affected by Alzheimer's disease, and the extra parkin seems to help clear them. That allows the cells to produce new and healthy mitochondria. ... With a normal amount of parkin, the cells are overwhelmed and cannot remove molecular debris. Extra parkin cleans everything." This should have much wider application, possibly even for the slowing of aging, given the broad role of autophagy; it's the sort of therapy that everyone would want done, regardless of their present state of health.

Monday, March 7, 2011
Ben Best here offers a critique of SENS, the Strategies for Engineered Negligible Senescence assembled by Aubrey de Grey, based on the absence of nuclear DNA damage from the list of things to repair: "Dr. de Grey asserts that repairing aging damage is a more effective approach than attempting to slow or prevent aging, and I agree with him. Being an ardent supporter of SENS has not stopped me from simultaneously being a critic of aspects of his program that I think are flawed or deficient. I will attempt to outline some of my criticisms in simple language, assuming that my readers have some knowledge of basic science. ... [a] fundamental concern that I have that a significant form of aging damage may be being ignored by SENS. ... There are many types of DNA damage, but for the purposes of this essay I will focus on breakage of both DNA strands - resulting in a gap in a chromosome. There are two mechanisms for repairing double-strand DNA breaks: Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). HR usually results in perfect repair, but HR can only operate when cells are dividing. NHEJ is the more frequent form of double-strand break repair, but it is error-prone. NHEJ is the only DNA repair mechanism available for non-dividing cells. Even in cells that divide, 75% of double-strand breaks are repaired by NHEJ. ... It is hard to believe that it could be a coincidence that the most notorious 'accelerated aging' diseases are due to defective DNA repair. ... Nuclear DNA damage typically leads to mutation or DNA repair - or apoptosis or cellular senescence when DNA repair fails (a mechanism that is believed to have evolved for protection against cancer). But not all DNA damage is repaired, and NHEJ repair is often defective. Accumulating DNA damage and mutation can lead to increasingly dysfunctional cells." Everyone in the community should have a go at critiquing SENS - because doing so forces you to do some digging and think it through for yourself, at which point you'll find that many aspects of biotechnology and human cellular biology are not as intimidating or as hard to understand as they might appear at a distance.

Monday, March 7, 2011
Thoughts on large systems, communications, scientific progress, and evolutionary theory from h+ Magazine: "What do the Global Brain (GB) and human biological immortality have in common? At first, this appears to be a strange question. However, I believe that the realisation of the Global Brain will, perhaps inevitably, result in humans achieving extreme life extension, and eventually abolishing death due to aging. The GB is an emergent worldwide entity of distributed intelligence, one facilitated by communication and the meaningful interconnections between billions of humans, via technology such as the internet. ... When fully operational, the GB must rely on its individual constituents - individual human brains interconnected through technology. Without human input, the GB cannot exist. Furthermore, it cannot exist without technology. This is similar to the human brain - a neuron contributes to the whole, but without suitable connections, the individual neuron does not survive. This is not a magical or fictional process. The sequence of events will happen according to natural laws. Human brains, as individual units of the GB, will be subjected to increased pressures that facilitate longer survival. This is not a teleological argument. The GB does not have any intent or purpose. It is just an instrument of nature, forming part of the general direction of evolution from simple to complex. Within our specific niche, dependent on technology, society and communication, we must adapt and evolve quickly in order to be successful. A hierarchical progress from simple to higher intelligence is a natural consequence (or requirement) of this. It follows that nature will favor mechanisms that lead to higher intelligence quickly, abandoning slow, non-specific mechanisms, such as traditional natural selection. Resources will be shifted from primarily maintaining the germline at the expense of the body (the slow process of natural selection), to maintaining the brain (a fast process for achieving higher intellectual complexity)."



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