Fight Aging! Newsletter, December 19th 2011

December 19th 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!



- The Latest Mitochondrially Targeted Antioxidant Research
- Towards Replacement Neurons for Parkinson's Disease
- An Example of Mainstream Optimism
- An Introduction to Reactive Oxygen Species and Aging
- Discussion
- Latest Headlines from Fight Aging!


Russian researchers continue to expand their study of plastiquinone compounds, antioxidants that target themselves to the mitochondria in cells even when ingested:

"The body and its cells are a vast city of many roads, a complex system that acts to steer all incoming chemicals into narrow, specific paths. The research of recent years suggests that ingested antioxidants from the store really don't do much because they will never end up face to face with the oxidative compounds that matter, or in the places that matter. This, at least, is the supposition because researchers have demonstrated ways to push antioxidants to where they do matter, and have extended life in mice by doing this.

"The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. ... For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions.

"SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice, [while] male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice [lived] as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system."


Here is news of progress that leads away from cell transplants and towards ways to direct the brain to produce suitable replacement cells by itself:

"Parkinson's researchers were among the first to earnestly attempt to create a specific cell type for transplant, and have continued to work at this. The obvious symptoms of Parkinson's are caused by the progressive loss of a thin population of dopamine-producing neurons, and therefore a way of replacing those specialist cells wholesale would be a way to temporarily reverse the course of the disease - perhaps for years or even decades in the best case. Thus these researchers now make up one of the more experienced scientific communities involved in cell therapy research, and can be counted on to rapidly pick up promising new developments in the control and reprogramming of cells.

"Once researchers have demonstrated control over cellular reprogramming, the ability to turn one cell type into another by providing suitable signals, the focus starts to shift away from transplants and on to reprogramming cells in situ: instructing the body - or the brain in this case - to directly produce more of the needed cell type. ... I'll go out on a limb and suggest that transplants are probably not the be-all and end end-all future of tissue engineering. By the time the 2020s roll around, I'd guess that most of the new therapies moving into US trials and clinical use overseas will be based on delivering increasingly precise and targeted reprogramming instructions into the body rather than introducing new cells or taking the patient's cells and working with them outside the body to produce tissue for transplantation."


The mainstream of our culture generally doesn't look much beyond exercise, the politics of redistribution, and the newfangled science of longevity genes when it comes to aging. But nonetheless, there are optimists writing within that narrow space, even if they manage to miss the most important research (such as SENS) and its implications:

"'Genes account for one-fourth to one-third of longevity,' estimated Howard Friedman, a professor of psychology at the University of California (Riverside) and the coauthor of The Longevity Project, published this year. 'That leaves well over half not accounted for.' Most of the rest, for better or worse, is up to you. 'The importance of choices people make is in so many ways responsible for the quality of life in old age,' said Charles Reynolds III, a professor of geriatric psychiatry, neurology, and neuroscience at the University of Pittsburgh medical school. 'Many people think they should be entitled to a good-quality 25 years after age 60. Well, they're not necessarily entitled, but they can put the odds in their favor.' One way - "the least speculative and the most obvious' - is with exercise, according to Simon Melov, a Buck Institute biochemist. 'More activity is better than no activity, and most people are not doing anything. They're just sitting there.' Exercise, he said, reduces the risk of cardiovascular disease and perhaps even a decline in cognition. One needn't run a marathon. Gardening, walking, swimming, woodworking - all of these are more active than just sitting."

The most important choice, not mentioned of course, is to support research and development of rejuvenation biotechnology. The future won't make itself, and unless we choose to build ways to reverse aging, they simply won't happen:


Nothing is simple or straightforward in the operation of our metabolism, and understanding that should help to generate an appropriate level of skepticism for the claims of supplement, pill, and potion salespeople:

"Reactive oxygen species (ROS) are damaging molecules that can rip up important cellular machinery; all machinery in a cell is an arrangement of atoms, and promiscuously reactive molecules can gum up the works, pull out important parts of the machinery, and otherwise cause all sorts of issues. In discussions of our biology, the term free radical is often used interchangeably to refer to these reactive molecules. They are produced within our cells as a byproduct of some of the most important mechanisms of metabolism, a fact shared by the vast majority of species, dating back far into evolutionary time. As for all aspects of cellular chemistry with such deep origins, evolution has has a very long time indeed in which to build feedback loops and interlaced machinery that depend upon the existence of ROS, co-opting these molecules for diverse purposes in signaling and regulating the operation of cells and tissues. Thus ROS generation and damage is not just a harmful side-effect of being alive and having cells that are churning away, but it is also fundamental to the complex processes by which our metabolism maintains cellular homeostasis in the face of day to day challenges."


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, December 16, 2011
One of the ways in which general health practices - such as exercise and fitness - steer cognitive health is through the state of the blood vessels in your brain: if they are deteriorating more rapidly, then more microinfarcts will occur, destroying more of the function of the brain, one tiny piece at a time. This is a mechanism quite distinct from the root causes of dementias like Alzheimer's disease, as this study illustrates: "This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF). ... Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately. ... In those with no dementia, MBIs were strongly associated with the last antemortem CF score ... This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop."

Friday, December 16, 2011
Opposition to enhanced human longevity, which often advocates collectivism and the use of government force to prevent other people from extending their lives through biotechnology, is based on a range of factors: fear of change, the green-eyed monster of envy (who has set up shop in the environmentalist movement these days), and ignorance of basic economics. In the latter case, some folk naively believe all resources to be limited - jobs, wealth, and so forth - rather than growing with population and length of life. But all of these things are made by people, and the more people there are and the longer those people live in good health, the more creation will take place. But there are always naysayers who have convinced themselves that a hundred thousand deaths due to aging every day and the ongoing suffering of hundreds of millions is necessary because of their own vague and unrealized anxieties about the future. Here is one example: "Wolpe's own perspective is that our drive toward immortality is basically selfish. He sees few benefits to society, and a good deal of potential harm, in our living to 200 or beyond. ... There is a natural wisdom in replacing us. There's a natural wisdom in the idea that new people who arise in new circumstances have new perspectives on the world. ... Look at the generations living now from the World War II generation to the Baby Boomers, to Gen-X, all the way down. The young generation today, the people in their teens and 20's today were steeped in a different brine than I was as a Baby Boomer. They were brought up with technology at their fingertips. They move naturally and easily through that world. And the idea that if I got to live to, you know, 150 or 200, that that would be a good thing for anyone other than me, I think is a misguided notion. And there's a deep selfishness in the move towards immortality and these people like Aubrey de Grey and others who are really looking for that Fountain of Youth. ... If we don't change, for example, reproduction, if reproduction stayed between let's say, 20 and 40, that means that you would have another 80 years after reproducing that you'd be around. So there's even the question of how we're going to restructure the human lifespan. Is that a proper dynamic to have your children and then live another hundred years?" As usual, this is airy nonsense when held up against the reality of the vast and pervasive suffering caused by aging - suffering that we can work to address instead of just waffling about intangibles.

Thursday, December 15, 2011
A progressive build up of advanced glycation end products (AGEs) is implicated in the aging process; they contribute to skin aging, for example. There are some research programs aimed at producing drugs or other treatments to break down the important AGEs in humans, but far too few of them, and poorly funded. Here, researchers look at AGEs in a mole rat species: "Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen."

Thursday, December 15, 2011
Correlations between character traits and longevity seem to be a growing area of study; interesting results, though of dubious importance, I think: "The relationship between personality and life span is not well understood, and no study to date has examined genetic influences underlying this relationship. The present study aimed to explore the phenotypic and genetic relationship between personality and life span, as well as genetic influences on all-cause mortality. ... Prospective community-based study including 3752 twin individuals older than 50 years. Neuroticism, psychoticism, extraversion, and social desirability and pessimism/optimism were measured at baseline using the Revised Eysenck Personality Questionnaire and the Revised Life Orientation Test, respectively. Information on age at death was obtained 16 years after the initial assessment of personality. ... Extraversion was inversely related to mortality with the risk of death decreasing 3% per unit increase of the extraversion score. Psychoticism and pessimism were positively related to mortality with a 36% and 39% increase in risk of death per unit increase in the respective personality score. Heritability of life span was 7%. ... Extraversion, psychoticism, and optimism/pessimism are significant predictors of longevity; extraversion is associated with a reduction, and pessimism and psychoticism are associated with an increase in mortality risk. Genetic influences on longevity in Australian twins are very low (7%). Our data also suggest a small, albeit nonsignificant, genetic influence on the relationship of pessimism and psychoticism with life span."

Wednesday, December 14, 2011
Via EurekAlert!: [Researchers] have developed a jelly-like material and wound treatment method that, in early experiments on skin damaged by severe burns, appeared to regenerate healthy, scar-free tissue. ... the researchers reported their promising results from mouse tissue tests. The new treatment has not yet been tested on human patients. But the researchers say the procedure, which promotes the formation of new blood vessels and skin, including hair follicles, could lead to greatly improved healing ... the hydrogel is constructed in such a way that it allows tissue regeneration and blood vessel formation to occur very quickly. ... Inflammatory cells are able to easily penetrate and degrade the hydrogel, enabling blood vessels to fill in and support wound healing and the growth of new tissue ... For burns, the faster this process occurs, [the] less there is a chance for scarring. Originally, [the] team intended to load the gel with stem cells and infuse it with growth factors to trigger and direct the tissue development. Instead, they tested the gel alone [and] were surprised to see such complete regeneration in the absence of any added biological signals. ... The hydrogel is mainly made of water with dissolved dextran, a polysaccharide (sugar molecule chains). ... It also could be that the physical structure of the hydrogel guides the repair .. [Researchers speculate] that the hydrogel may recruit circulating bone marrow stem cells in the bloodstream. ... It's possible the gel is somehow signaling the stem cells to become new skin and blood vessels."

Wednesday, December 14, 2011
The use of nanoparticles to precisely deliver compounds to cells and specific locations within cells has a far broader application than just cancer therapies. Any existing drug that can be targeted this way can be made far more effective: provided in much smaller doses and with greatly reduced side-effects. For example: "Hitching a ride into the retina on nanoparticles called dendrimers offers a new way to treat age-related macular degeneration and retinitis pigmentosa. A study [shows] that steroids attached to the dendrimers target the damage-causing cells associated with neuroinflammation, leaving the rest of the eye unaffected and preserving vision. ... There is no cure for these diseases. An effective treatment could offer hope to hundreds of millions of patients worldwide. ... [Researchers] tested the dendrimer delivery system in rats that develop neuroinflammation. The target was microglial cells, inflammatory cells in charge of cleaning up dead and dying material in the eye ... When activated as 'trash collectors,' the cells cause damage via neuroinflammation - a hallmark of each disease. The microglial cells gobble up the dendrimers, and the drug then shuts down the cells' activity. ... Surprisingly, the activated microglia in the degenerating retina appeared to eat the dendrimer selectively, and retain them for at least a month. The drug is released from the dendrimer in a sustained fashion inside these cells, offering targeted neuroprotection to the retina. ... The treatment reduced neuroinflammation in the rat model and protected vision by preventing injury to photoreceptors in the retina. Though the steroid offers only temporary protection, the treatment as a whole provides sustained relief from neuroinflammation."

Tuesday, December 13, 2011
Clinical studies in which tissue is grown from a patient's own cells and then implanted to address a medical issue are no longer remarkable; many are currently taking place, with new studies starting all the time. A surprising number of these are focused on pediatric medicine, but the technologies have the prospect of much broader application. Here is an example: "Xeltis, a biomedical technology company developing growing, living and self-healing cardiovascular implants using tissue-engineering technology, has announced conditional approval by the Paul Erlich Institute (PEI) in Germany to commence the first clinical study of its tissue-engineered cardiovascular grafts. The prospective, single-center study will evaluate the safety and efficacy of Xeltis' autologous tissue-engineered vascular grafts in pediatric patients ... Due to their expected longevity, ability to grow and very low risk of thrombosis and infection, these new grafts hold the promise to deliver life-saving therapy for children born with cardiovascular defects. ... Today's grafts are made of artificial material or of animal tissue, both having significant limitations such as potential rejection, limited durability and calcification over time. In contrast, Xeltis implants are 'regrown' from the patients' own cells. The resulting implants are, therefore, designed to behave like native organs, with unlimited durability, no risk of rejection and no need for anticoagulants. In addition, children implanted with today's grafts face the critical problem of outgrowing their implants, requiring them to undergo one or more reoperations, each with an increasing rate of morbidity. Because Xeltis' implants have the ability to grow as the child grows, they may remove the need for reoperations."

Tuesday, December 13, 2011
Via EurekAlert!: researcher have "developed a new method to design antibodies aimed at combating disease. The surprisingly simple process was used to make antibodies that neutralize the harmful protein particles that lead to Alzheimer's disease. ... Antibodies are large proteins produced by the immune system to combat infection and disease. ... Scientists have long sought methods for designing antibodies to combat specific ailments. However, the incredible complexity of designing antibodies that only attached to a target molecule of interest has prevented scientists from realizing this ambitious goal. When trying to design an antibody, the arrangement and sequence of the antibody loops is of utmost importance. Only a very specific combination of antibody loops will bind to and neutralize each target. ... The new antibody design process was used to create antibodies that target a devastating molecule in the body: the Alzheimer's protein. ... We are actually exploiting the same protein interactions that cause the disease in the brain to mediate binding of antibodies to toxic Alzheimer's protein particles ... Alzheimer's disease is due to a specific protein - the Alzheimer's protein - sticking together to form protein particles. These particles then damage the normal, healthy functions of the brain. The formation of similar toxic protein particles is central to diseases such as Parkinson's and mad cow disease. Importantly, the new Alzheimer's antibodies [only] latched on to the harmful clumped proteins and not the harmless monomers or single peptides that are not associated with disease. [Researchers] see the potential for their technique being used to target and better understand similar types of protein particles in disorders such as Parkinson's disease.

Monday, December 12, 2011
A couple of videos on economics and engineered longevity, by G. Stolyarov II and Aubrey de Grey: "Mr. Stolyarov discusses how indefinite human life extension will bring about numerous economic benefits to human beings and human civilization. He approaches the subject from the standpoint of the idea of time preference and the time horizons that would be greatly expanded for humans who live much longer. Furthermore, indefinite human longevity will enable humans to confront major existential threats - such as the threat of a meteor impact or a new ice age - that are beyond the timeframe of the individual lifespan today. ... Radical life extension would have a huge impact on the economics of society - possibly a dangerous one. Aubrey de Grey explains why he remains optimistic that the economy would adapt well to the drastically new paradigm presented by human immortality." Sadly, there's always someone out there who thinks that extended healthy human life is dangerous, despite the evidence of past centuries and many regions of the world that show greater life expectancy walks hand in hand with economic growth and higher standards of living. This is one of the reasons that advocacy for longevity science is even necessary in the first place. Nonetheless, the two upward trends of longevity and wealth are entwined and drive one another wherever they can start. But despite living in an age of change, so very many people fear change to the point of rejecting it even when it is overwhelmingly positive.

Monday, December 12, 2011
You might recall that researchers are making efforts to correlate psychological states, such as character traits and stress, with aging and the biochemistry of aging. Here is another item from that side of the field: researchers "have now shown that sirtuins likely also play a key role in the psychological response to dietary restriction. When sirtuins are elevated in the brain, as occurs when food intake is cut, mice become much more anxious. Furthermore, in two large genetic studies of humans, the team found that mutations that boost production of sirtuins are commonly associated with higher rates of anxiety and panic disorder. The researchers believe that this anxiety may be an evolutionary adaption that makes animals - including humans - more cautious under the stressful condition of having to forage more widely for scarce food. ... It makes sense, because behavior effects would be as adaptive, and as selected by evolution, as physiological effects. I don't think it's surprising that behavior really falls under the umbrella of natural selection." Of course there is uncertainty over whether sirtuins are actually important as drivers of the enhanced longevity produced by calorie restriction.



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