Longevity Meme Newsletter, October 04 2010

October 04 2010

The Longevity Meme 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 the Longevity Meme.



- The Future of Aging
- The Era of Engineered Cells
- The First Foundations of Artificial Eyes
- Discussion
- Latest Healthy Life Extension Headlines


The Future of Aging is a forthcoming book with chapters contributed by many of the well known names in modern aging and longevity science:


"Just as the health costs of aging threaten to bankrupt developed countries, this book makes the scientific case that a biological 'bailout' could be on the way, and that human aging can be different in the future than it is today. Here 40 authors argue how our improving understanding of the biology of aging and selected technologies should enable the successful use of many different and complementary methods for ameliorating aging, and why such interventions are appropriate based on our current historical, anthropological, philosophical, ethical, evolutionary, and biological context. Challenging concepts are presented together with in-depth reviews and paradigm-breaking proposals that collectively illustrate the potential for changing aging as never before.

"The proposals extend from today to a future many decades from now in which the control of aging may become effectively complete. Examples include sirtuin-modulating pills, new concepts for attacking cardiovascular disease and cancer, mitochondrial rejuvenation, stem cell therapies and regeneration, tissue reconstruction, telomere maintenance, prevention of immunosenescence, extracellular rejuvenation, artificial DNA repair, and full deployment of nanotechnology. The Future of Aging will make you think about aging differently and is a challenge to all of us to open our eyes to the future therapeutic potential of biogerontology."


We live in an age of biotechnology, and we ourselves are made of machines open to manipulation and improvement:


"Our cells are very versatile and complex machines, really an assemblage of many such machines. As researchers make inroads into understanding the details of the mechanisms, they will become ever more capable of manipulating and engineering cells. The earliest meaningful efforts here are focused on (a) trying to change the high level state of the cell, to turn an ordinary cell into a stem cell, for example, and (b) directing cells to undertake specific actions by issuing chemical signals, such as efforts to spur stem cells into greater feats of regeneration.

"In the future, engineering cellular state and behavior will become a very broad technology platform indeed. Almost any part of the cell is open to change, enhancement, or outright replacement if fully understood. We couldn't possibly predict all of what will be accomplished here: engineered cells may be turned into medical instruments, for example, programmed to construct drugs and move through the body to where those drugs are needed. Entire classes of cells, such as immune system cells, may be retired to be replaced with more efficient versions. And so forth.

"Here and now, however, this line of research is still just beginning. The cutting edge today is focused on infrastructural needs, such as low cost and reliable production of stem cells. Half the battle here is finding ways to build the tools of research cheaply enough to allow a much larger research community to join in - a hundred labs produce a far greater diversity of results than ten."


Present day work focused on working around the degenerative loss of sight is just the first step in a long road towards entirely artificial eyes:


"In comparison to work on artificial hearts and kidneys, development of artificial eyes lags far behind - it's a challenging problem and the eye is arguably a more complex system than anything else outside the brain. The present mainstream approach involves building a grid of electrodes in place of the retinal cells lost to forms of degenerative blindness; images captured by a worn camera are analyzed and the electrodes stimulated appropriately.

"Progress in this model is at present a matter of making implantation safer and more reliable, greatly increasing the density of electrodes, and improving the ability to translate a camera's view into a helpful picture - a combination of medicine, electrical engineering, and computer vision research. The end result of this form of technology will never produce anything more than a detailed, glowing sketch of dots and lines for the patient: it is not true vision as experienced by those of us fortune enough to retain our sight. Nonetheless it works - already providing a great improvement for patients over being blind - and it will serve as a foundation for later forms of artificial sight technology. An established research and development community doesn't stand still after the first products are commercialized, but rather moves onward to new breakthroughs."


The highlights and headlines from the past week follow below.

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The Economist looks at an intriguing research discovery: "The one sure way to prolong an animal's life is, paradoxically, to starve it. 'Caloric restriction', as it is known in the trade, works for everything from threadworms to mammals (people included, as far as can be ascertained without the luxury of controlled experiments). So it is no surprise that it also works for a group of small creatures known as rotifers. ... What makes this news is that the offspring of the rotifers in question also lived longer than normal. And that - the inheritance of an acquired characteristic - is quite startling. ... the offspring of calorie-restricted mothers have more catalase than those of mothers who were fed without restriction. The researchers also detected higher levels of the enzyme in the eggs of calorie-restricted mothers, so it could be that their offspring are simply endowed with the stuff. A more intriguing possibility, though, is that the relevant genes are affected by epigenesis, a process in which chemicals attached to the DNA control its activity. Epigenetic modifications are often retained when cells divide, and can sometimes be passed on to offspring." You'll recall that catalase gene engineered to localize in mitochondria can be used to extend life in mice. Researchers will now have to check to see if mammals reproduce any of this inherited catalase effect seen in rotifers.

Here, an Australian radio show looks at Werner syndrome, an accelerated aging condition that appears to be one aspect of normal aging run amok: "People with Werner syndrome age quickly in their early 20s and at this age can look as though they are 70 years old. They die prematurely of old age and show all the signs of normal ageing. There are only 200 known cases in the world. It is caused by the loss of function of one gene and is a perfect model for ageing. This research is assisting in understanding the biochemical pathways of older people's health and may lead to treatments to improve the health of older people." As is the case for progeria, it is possible that therapies for the accelerated aging conditions may have some application in normal aging - it depends on how greatly the specific biochemical dysfunctions involved contribute to "normal" age-related degeneration. My own sense is that they are not in fact important in comparison to the forms of biochemical and cellular damage outlined in the Strategies for Engineered Negligible Senescence, but I'm not aware of any rigorous analysis to back that up that sentiment.

The relationship between excess fat tissue and dementia is well known, and researchers continue to investigate the details: "Adipose tissue is an endocrine and paracrine organ that contributes to both metabolic and vascular homeostasis. Overweight and obesity due to excess adipose tissue, are cornerstones of vascular risk and increase risk for late-onset dementia. Vascular risk does not exist in isolation, and is accompanied by alterations in hormonal metabolism and metabolic syndromes. Thus, while vascular risk is highlighted as a primary mechanism for elevated dementia occurrence due to obesity, hormonal risk states may also precede or result from underlying dementia-related neuropathologies and direct neuronal toxicity. This is exemplified during the prodromal phase of dementia, as vascular and metabolic parameters decline in relation to dementia development, and potentially in a way that is different from 'normal' aging. In this review will be presented a review of the epidemiology of adiposity and dementia; adipose tissue biology; and two major hormones produced by adipose tissue, leptin and adiponectin, that interact directly with the brain. ... Understanding the role of adipose tissue in health of the brain is pivotal to a deeper understanding of dementia processes."

Via the Detroit News: "trials are being conducted on women with advanced stage breast cancer and attempt to target the cancer's stem cells, which are believed to be resistant to traditional therapies and the fuel behind cancer's spread. By using experimental drugs to block these cancer stem cells, doctors hope the tumors will shrink or at least stop spreading and will lead to better ways to treat - and possibly cure - the disease that is the nation's second-leading cause of death. ... We rarely use the 'C word' - cure - but the intent of research today is not to study (cancer) but to treat and ultimately to beat it. There is so much hope that we're positioned today with the information from the (human) genome, with the biologic expertise and understanding of the stem cells, I think we can be at the vanguard of treatments that hopefully will lead toward not just longer, disease-free survival but quite literally cures. That's the hope of the cancer stem cell approach. ... In breast cancer, we have very good results of getting rid of the primary cancer with surgery or radiation therapy but what is lethal to a number of women who actually die of breast cancer is the spread of the cancer. These cancer stem cells are the cells that are metastatic. That's why we had to develop new approaches to target these cancer stem cells if we are going to cure more women with breast cancer and other types of cancer."

Via EurekAlert!, signs of continued progress in understanding how to give orders to cells: "scientists have found a way to regenerate injured spinal cord and muscle by using small molecule drugs to trigger an influx of sodium ions into injured cells. The approach breaks new ground in the field of biomedicine because it requires no gene therapy; can be administered after an injury has occurred and even after the wound has healed over; and is bioelectric, rather than chemically based. ... Like human beings, who regenerate fingertips only as children, [tadpoles] lose the ability to regenerate their tail with age. Most remarkably, it was shown that [tadpoles] whose tails had been removed could be induced to make a perfect new tail by only an hour of treatment with a specific drug cocktail. The findings have tremendous implications for treating wounds ... The treatment method used is most directly applicable to spinal cord repair and limb loss, which are highly significant medical problems world-wide. It also demonstrates a proof-of-principle that may be applicable to many complex organs and tissues. ... We have significantly extended the effective treatment window, demonstrating that even after scar-like wound covering begins to form, control of physiological signals can still induce regeneration. Artificially causing an influx of sodium for just one hour can overcome a variety of problems, such as the decline in regenerative ability that comes with age and the effect of regeneration-blocking drugs."

A good demonstration of dental tissue engineering: researchers "used stem cells obtained from the periodontal ligament of molars extracted from mice, expanded them in an incubator, and then seeded them on barren rat molars. The stem cell-treated molars were reinserted into the tooth sockets of rats. After two and four months, the stem cells aligned and formed new fibrous attachments between the tooth and bone, firmly attaching the replanted tooth into the animal's mouth ... Tissue sections showed that the replanted tooth was surrounded by newly formed, functional periodontal ligament fibers and new cementum, the essential ingredients of a healthy tooth attachment. ... To verify that the ligament was formed by the transplanted stem cells and not by the animal's own cells, stem cells were labeled with green fluorescent protein prior to seeding them on the molars and re-inserting the teeth into the animal's mouth. ... Our research uncovered the code required to reattach teeth - a combination of natural tooth root surface structure together with periodontal progenitor cells. ... Our strategy could be used for replanting teeth that were lost due to trauma or as a novel approach for tooth replacement using tooth-shaped replicas."

Michael Anissimov notes that a new cryonics support organization is starting up in Europe: "EUCRIO will officially launch on Friday, October 1st. ... EUCRIO is an organization that specializes in providing state-of-the-art standby, stabilization, and transport procedures for cryonicists in the European Union. EUCRIO is pleased to assist members of the three main cryonics storage provider organizations. ... If one of our members has an emergency we deploy our trained and well-equipped team to stand-by the patient's bedside, ready to give the best stabilization services. The patient is given stabilization medications, cooled down, and perfused with vitrification solutions before further cooling to dry ice temperatures for air-transport to the appropriate cryonics organization for long-term preservation using liquid nitrogen. Our primary mission is to improve human cryopreservation and safeguard the lives of our members. ... EUCRIO employs a wide variety of professionals: including physicians, perfusionists, emergency medical technicians, engineers and scientists, throughout the European Union. EUCRIO has staff members ready to intervene across the European Union and all are ready to respond to clients at all times." As I've remarked in the past, the support and infrastructure for conducting cryopreservation events is an area in need of both improvement and more participation. The actual provision of ongoing low temperature storage for the recently deceased, while a challenge in and of itself, is easy in comparison to managing end of life issues and a timely cryopreservation.

A paper to go along with a recent demonstration of in situ regeneration of enamel: "The regenerative capability of enamel, the hardest tissue in the vertebrate body, is fundamentally limited due to cell apoptosis following maturation of the tissue. Synthetic strategies to promote enamel formation have the potential to repair damage, increase the longevity of teeth and improve the understanding of the events leading to tissue formation. Using a self-assembling bioactive matrix, we demonstrate the ability to [induce] formation of enamel at chosen sites adjacent to a mouse incisor cultured in vivo under the kidney capsule. The resulting material reveals the highly organized, hierarchical structure of hydroxyapatite crystallites similar to native enamel. This artificially triggered formation of organized mineral demonstrates a pathway for developing cell fabricated materials for treatment of dental caries, the most ubiquitous disease in man. Additionally, the artificial matrix provides a unique tool to probe cellular mechanisms involved in tissue formation further enabling the development of tooth organ replacements."

Biomedical gerontologist Aubrey de Grey notes: "This October, Hannover and Detroit will host two of the year's most interesting and wide-ranging scientific conferences in the biomedical field. I'll be chairing sessions at both events, focused on the application of regenerative medicine to aging and aging-related disease - a synergy we at SENS Foundation term rejuvenation biotechnology. ... The World Stem Cell Summit - hosted this year in Detroit, Michigan from October 4th to 6th - is a wide-ranging event covering topics from basic research to social policy and ethics, and expected this year to attract more than 1,200 delegates from 30 nations. I'll be chairing a session at the summit entitled "Regenerative Medicine Against Aging - Technological, Political and Commercial Obstacles and Opportunities". Participants include Dan Perry, of the Alliance for Aging Research; Michael West, acclaimed biotechnology entrepreneur and CEO of Biotime, Inc.; and Huber Warner, former associate director of the National Institute on Aging. ... The World Congress on Preventive and Regenerative Medicine, hosted this year in Hannover from October 5th-7th, is the only international event addressing the entire regenerative medicine sector. This broad remit, similar to that of the SENS conference series, gives the meeting outstanding potential to foster interdisciplinary collaborations in research and development. I am serving as a vice-president of the Congress, and will co-chair a session entitled "Rejuvenation Biotechnologies: Applying Regenerative Medicine to Aging"."

Eric Drexler writes on the topic of antioxidants and autophagy: "Autophagy removes cell components - including ROS-damaged proteins and organelles - by engulfing and digesting them, producing wastes and recycled nutrients. ... Upregulating autophagy [has] extraordinarily wide-ranging benefits. Interventions that extend healthy lifespan in animal models include calorie restriction, resveratrol, spermidine, and rapamycin, and in each operates, at least in part, through autophagy. Upregulating autophagy has positive effects in models of several specific neurodegenerative diseases, too ... antioxidants inhibit basal autophagy and block the induction of autophagy by calorie restriction and other means. Because this effect inhibits the central mechanism of cell repair, it helps explain why dietary antioxidants have failed to deliver their expected benefits to health and longevity." I would have said it has more to do with failing to target mitochondria, given the benefits demonstrated by mitochondrially targeted antioxidants. As Drexler notes, however, there's research to back up the antioxidant-autophagy link, which may have some relation to earlier research showing antioxidant supplementation to interfere with the processes of hormesis, and thus block beneficial effects of mild stress such as exercise.



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