Researchers here examine the published literature on hormesis via heat shock, one of the ways shown to induce modest gains in longevity in laboratory animals, and find less support for positive outcomes than was thought. This may or may not be significant & the goal for researchers, as for calorie restriction and other means of extending longevity, is to find the underlying mechanism of action and build a therapy that triggers it with minimal side-effects. So long as heat shock can be demonstrated to improve long term health and longevity under at least some conditions, then there is a mechanism to be found and exploited.

Hormesis is the response of organisms to a mild stressor resulting in improved health and longevity. Mild heat shocks have been thought to induce hormetic response because they promote increased activity of heat shock proteins (HSPs), which may extend lifespan. Using data from 27 studies on 12 animal species, we performed a comparative meta-analysis to quantify the effect of heat shock exposure on longevity. Contrary to our expectations, heat shock did not measurably increase longevity in the overall meta-analysis, although we observed much heterogeneity among studies.

Thus, we explored the relative contributions of different experimental variables (i.e. moderators). Higher temperatures, longer durations of heat shock exposure, increased shock repeat and less time between repeat shocks, all decreased the likelihood of a life-extending effect, as would be expected when a hormetic response crosses the threshold to being a damaging exposure. We conclude that there is limited evidence that mild heat stress is a universal way of promoting longevity at the whole-organism level. Life extension via heat-induced hormesis is likely to be constrained to a narrow parameter window of experimental conditions.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23570942

Source:
http://www.fightaging.org/archives/2013/04/limited-evidence-for-the-universality-of-heat-shock-hormesis-as-a-way-to-induce-longevity.php

Source:
http://www.longevitymedicine.tv/limited-evidence-for-the-universality-of-heat-shock-hormesis-as-a-way-to-induce-longevity/

When it comes to medical procedures, everyone has their own definition of acceptable risk. Sadly we&re then overruled by faceless bureaucrats at the US Food and Drug Administration (FDA) and similar government bodies & people who have only their own interests in mind, and suffer no consequences from making useful medical technologies illegal or too expensive for commercial use. Fortunately, the FDA doesn&t rule the world: there are regions in which medical regulations are less onerous and therapies less costly, and these locations are only a plane flight away.

People who undertake medical tourism for stem cell therapies are demonstrating their own risk preferences: balancing the plausible expected benefits based on what is presently known of the science and the outcomes (in the absence of rigorous trials) against the cost and estimated risk. For stem cell treatments perhaps the largest inherent risk for early stage therapies is that of cancer resulting from the activities of transplanted cells. Work in the laboratory suggests that this risk is generally lower than first thought, but it still exists.

The world of cancer treatments is, meanwhile, changing profoundly, gearing up for a new generation of therapies that will displace chemotherapy and radiotherapy. Reprogramming immune cells or introducing targeted viruses and nanoparticles to seek out and kill cancer cells with few side-effects will be the standard operating procedure twenty years from now & and probably available outside the US in a decade. In early trials and the laboratory, these technologies are already showing impressive results.

Improvements in cancer treatment & leading to the introduction of robust therapies that can clear most common forms of cancer quickly and without accompanying illness & will, I think, go hand in hand with a far greater demand for and use of very aggressive stem cell treatments. Things like periodic infusions of massive numbers of immune cells cloned from a patient&s own cells, done not just for people with medical conditions, but for the healthy as a beneficial preventative measure. Similarly, why boost regeneration and tissue maintenance via stem cell therapies only in the sick and the wounded? That makes sense if there is a significant risk associated with treatment, but in a world in which cancer is merely troublesome, why not make stem cell therapies a part of general health maintenance?

These are the sort of shifts in the cost-benefit picture of regenerative medicine that will emerge over the next couple of decades, driven by a growing ability to control the undesirable aspects of cellular biology, such as cancer.

Source:
http://www.fightaging.org/archives/2013/04/robust-cancer-therapies-will-mean-a-greater-use-of-aggressive-stem-cell-therapies.php

Source:
http://www.longevitymedicine.tv/robust-cancer-therapies-will-mean-a-greater-use-of-aggressive-stem-cell-therapies/

A fair number of research groups worldwide are gathering and processing data in search of associations between minor genetic variations and human longevity. As for all studies of long-term human health, this a challenging process: statistics become involved, it is costly to gather data of even moderate quality, and the underlying biology is exceedingly complex. This is illustrated by the fact that comparatively few genetic associations can be validated across different study populations: if you find a genetic polymorphism with a statistically significant association with longevity in Italian lineages, the odds are very good that it won&t show up in Asian populations, or even in other Italian study populations, for that matter. The range of minor variation in the human genome is very large, and it seems to be the case that there are many, many tiny genetic contributions to the way in which metabolism interacts with environment to determine natural longevity, most of which differ widely in different populations.

So while the funding lasts, this is a deep well for researchers to work on & just not one likely to produce more than knowledge for the foreseeable future. If you want actual results in terms of therapies to reverse the course of aging, then look to the programs described in the SENS research outline. The research community already knows what needs to be repaired in aged tissue, as the low-level differences between old and young tissue are well enumerated & it is the intricate, enormously complex metabolic dance of progressing from undamaged to damaged that remains an open field of work. The difference between SENS and the mainstream efforts to fully understand aging is the difference between on the one hand making the effort to rust-proof a metal surface and on the other producing a complete and detailed model of how rust progresses and interacts with metal structures at every level, from chemistry through to the physics of forces acting on structures and material strengths. The latter isn&t necessary to achieve the goal of prevention once you know what rust is, and indeed will probably prove to cost far more than just preventing the rust.

Here are a couple of illustrative papers from the steady flow of new associative studies of genetics and aging in humans. There will be many more similar results arriving in the years ahead: a lot more money goes towards this sort of work than to any effort to do something about aging.

The functional VNTR MNS16A of the TERT gene is associated with human longevity in a population of Central Italy

Telomerase, encoded by TERT, is the ribonucleoprotein polymerase that maintains telomere ends and it plays a crucial role in cellular senescence. TERT single nucleotide polymorphisms (SNPs) have been associated both with various malignancies and telomere length (TL). The association of TERT SNPs with longevity remains uncertain and varies with ethnicity. Aim of this study was to investigate whether the functional variable number of tandem repeat (VNTR) MNS16A of TERT is associated with longevity.

MNS16A genotypes have been determined for 1072 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes. MNS16A appears associated to longevity. The MNS16A*L allele is significantly underrepresented in Age Class 3 compared to Age Class 2. The concomitant significant telomere cross sectional attrition rate observed for L*/L* genotype suggests that this polymorphism could influences human longevity by affecting TL.

Common polymorphisms in nitric oxide synthase (NOS) genes influence quality of aging and longevity in humans

Nitric oxide (NO) triggers multiple signal transduction pathways and contributes to the control of numerous cellular functions. Previous studies have shown in model organisms that the alteration of NO production has important effects on aging and lifespan. We studied in a large sample (763 subjects, age range 19-107 years) the variability of the three human genes (NOS1, -2, -3) coding for the three isoforms of the NADPH-dependent enzymes named NO synthases (NOS) which are responsible of NO synthesis.

We found that gene variation of NOS1 and NOS2 was associated with longevity. In addition NOS1 rs1879417 was also found to be associated with a lower cognitive performance, while NOS2 rs2297518 polymorphism showed to be associated with physical performance. Moreover, SNPs in the NOS1 and NOS3 genes were respectively associated with the presence of depression symptoms and disability, two of the main factors affecting quality of life in older individuals. On the whole, our study shows that genetic variability of NOS genes has an effect on common age related phenotypes and longevity in humans as well as previously reported for model organisms.

Source:
http://www.fightaging.org/archives/2013/04/examples-of-genetic-association-studies-of-human-longevity.php

Source:
http://www.longevitymedicine.tv/examples-of-genetic-association-studies-of-human-longevity/

Here is a popular science article on intermittent fasting, something that extends life in mice, but which is not as well researched as calorie restriction, the gold standard for science on healthy life extension. There appears to be considerable overlap in the mechanisms involved in calorie restriction and intermittent fasting, but it&s not all exactly the same when gene expression patterns are examined, to pick one example.

Many diet and exercise trends have origins in legitimate science, though the facts tend to get distorted by the time they achieve mainstream popularity. Benefits are exaggerated. Risks are downplayed. Science takes a backseat to marketing. One needn&t look any further than the emerging trend of intermittent fasting for a prime example.

There is indeed a large body of research to support the health benefits of fasting, though most of it has been conducted on animals, not humans. Still, the results have been promising. Fasting has been shown to improve biomarkers of disease, reduce oxidative stress and preserve learning and memory functioning. [There] are several theories about why fasting provides physiological benefits. &The one that we&ve studied a lot, and designed experiments to test, is the hypothesis that during the fasting period, cells are under a mild stress. And they respond to the stress adaptively by enhancing their ability to cope with stress and, maybe, to resist disease.&

But perhaps it isn&t so much the fasting that produces health benefits, per se, as the resulting overall reduction in calorie intake (if, that is, you don&t overeat on nonfasting days, which could create a caloric surplus instead of a deficit). That appears, at least, to be the case in slowing diseases such as cancer in mice. &Caloric restriction, undernutrition without malnutrition, is the only experimental approach consistently shown to prolong survival in animal models,& In [a] study, mice fasted twice a week for 24 hours, but were otherwise permitted to eat at liberty. During nonfasting days, the mice overate. Overall, they did not lose weight, counteracting whatever benefits they might have seen from fasting. Intermittent fasting with compensatory overeating &did not improve mouse survival nor did it delay prostrate tumor growth,& the study concluded.

Equally, there are studies showing that intermittent fasting without calorie restriction does extend life in nematode worms. A lot more research is needed to bring intermittent fasting up to the level of confidence that we can have in calorie restriction.

Link: http://www.cmaj.ca/site/earlyreleases/8apr13_intermittent-fasting-the-science-of-going-without.xhtml

Source:
http://www.fightaging.org/archives/2013/04/on-intermittent-fasting-2.php

Source:
http://www.longevitymedicine.tv/on-intermittent-fasting/

An advance in the methodologies of nerve repair: "scientists believe a new procedure to repair severed nerves could result in patients recovering in days or weeks, rather than months or years. The team used a cellular mechanism similar to that used by many invertebrates to repair damage to nerve axons. ... We have developed a procedure which can repair severed nerves within minutes so that the behavior they control can be partially restored within days and often largely restored within two to four weeks. If further developed in clinical trials this approach would be a great advance on current procedures that usually imperfectly restore lost function within months at best. ... nerve axons of invertebrates which have been severed from their cell body do not degenerate within days, as happens with mammals, but can survive for months, or even years. The severed proximal nerve axon in invertebrates can also reconnect with its surviving distal nerve axon to produce much quicker and much better restoration of behaviour than occurs in mammals. ... Severed invertebrate nerve axons can reconnect proximal and distal ends of severed nerve axons within seven days, allowing a rate of behavioural recovery that is far superior to mammals. In mammals the severed distal axonal stump degenerates within three days and it can take nerve growths from proximal axonal stumps months or years to regenerate and restore use of muscles or sensory areas, often with less accuracy and with much less function being restored. ... The team described their success in applying this process to rats ... The team were able to repair severed sciatic nerves in the upper thigh, with results showing the rats were able to use their limb within a week and had much function restored within 2 to 4 weeks."

Link: http://www.eurekalert.org/pub_releases/2012-02/w-npr020112.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

It is not unreasonable to regard a cell as a machine that is constantly rebuilding itself - organelles and protein machinery are constantly torn down and replaced. It is also not unreasonable to regard tissue as a collection of cells that is constantly rebuilding itself: cells destroy themselves or are destroyed by watchdog systems, and new cells are created to replace them. This sort of thing happens rapidly indeed in some parts of the body, such as the blood and stomach lining, but there are portions of your nervous system where cells will never be replaced under normal circumstances - the cells you were born with are the very same cells you have now.

These long-lived cells are the most vulnerable to forms of age-related damage involving build up of metabolic waste products, and the related slow failure in the ability of cells to recycle their own damaged components. There is no fallback to replacing cells wholesale in this case, or at least not in our species, so long-lived cells must forge ahead and struggle to do their job no matter how damaged they are. The existence of these cells is a good argument for the need for in situ repair technologies, able to reverse damage and remove other hinderances in order to allow long-lived cells to regain their vigor and function - goals that are hard to attain with the present generation of cell replacement technologies emerging from the field of regenerative medicine.

Now consider this: it may be the case that some of the individual vital proteins in the machinery of long-lived cells are also never replaced. Some of your complex individual proteins, important cogs and gears in important cells, might be as old as you are. The very same sorts of concern about vulnerability surface here as well. Here is news of research in rats:

The scientists discovered that certain proteins, called extremely long-lived proteins (ELLPs), which are found on the surface of the nucleus of neurons, have a remarkably long lifespan. While the lifespan of most proteins totals two days or less, the Salk Institute researchers identified ELLPs in the rat brain that were as old as the organism. ... ELLPs make up the transport channels on the surface of the nucleus; gates that control what materials enter and exit. Their long lifespan might be an advantage if not for the wear-and-tear that these proteins experience over time. Unlike other proteins in the body, ELLPs are not replaced when they incur aberrant chemical modifications and other damage.

...

The fundamental defining feature of aging is an overall decline in the functional capacity of various organs such as the heart and the brain. This decline results from deterioration of the homeostasis, or internal stability, within the constituent cells of those organs. Recent research in several laboratories has linked breakdown of protein homeostasis to declining cell function. ... Most cells, but not neurons, combat functional deterioration of their protein components through the process of protein turnover, in which the potentially impaired parts of the proteins are replaced with new functional copies. Our results also suggest that nuclear pore deterioration might be a general aging mechanism leading to age-related defects in nuclear function, such as the loss of youthful gene expression programs.

Given how much longer humans live in comparison to rats, it may be that there are no proteins in the human body that never turn over. But I wouldn't be surprised to find that the situation for old humans is exactly the same as described above for old rats.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The SENS Research Foundation (SRF) funds research programs aimed at the development of rejuvenation biotechnology – i.e. the basis for medical therapies that can reverse degenerative aging and thus extend healthy, vigorous human life spans. These programs are based on the Strategies for Engineered Negligible Senescence (SENS) first outlined by Aubrey de Grey some years ago. I’m very much in favor of this: the work has to be done, the sooner the better, and the SRF is one of the few places in the world where you can make a donation and know that it’s going directly towards high-impact, relevant medical research into human rejuvenation.

I’m pleased to see this sort of thing taking place, for example: a company pledging a percentage of profits to the cause. There has been some discussion of pledging profits and stock in young companies in the past, and rejuvenation biotechnology is popular with the technology entrepreneur community.

Rescue Assist donates to SRF

Rescue Assist, Inc., a company developing a robotic product that readily maneuvers through debris and will help rescue workers find disaster survivors, has pledged 7% of its profits to SENS Research Foundation. Though the corporation was founded only a couple of years ago, it was profitable in 2012, and so has already begun to back SRF and its mission of transforming the way the world researches and treats the diseases of aging. “This is a great example of how entrepreneurs can support our work and our cause,” said Dr. Aubrey de Grey, SRF’s Chief Science Officer.

“Incorporating a pledge like this at the formation stage of a new company is one of the best ways to support a nonprofit,” said Glynn Burke, founder of Rescue Assist. “If this concept can be expanded by others, that would be a fantastic outcome.”

You can read the Foundation’s annual reports yourself to see how the money is being spent, and how the research and outreach moves forward year by year.

Getting the job done doesn’t mean doing it all yourself, however. Completing a demonstration of SENS in mice is sketched in at a decade and a billion dollars if fully funded, but that’s the opening scene in a longer play devoted to translating animal studies into human clinical medicine. The point of the SENS Research Foundation is to “completely redefine the way the world researches and treats aging and age-related diseases.” Some directly funded research is necessary to this goal, such as when fields are neglected and the research community needs a mix of a kick in the pants and an influx of philanthropic funding – as is the case for work on clearing out advanced glycation end-products from our tissues. But the larger aim is persuasion: persuade a large enough fraction of the research community to agree with with SENS vision of aging, and they will form their own labs and research initiatives to help.

In this sense, SENS is a peaceful revolution of the sort that roll through the world’s research communities with some regularity. In a way, SENS has already won its place as the forthcoming dominant paradigm, despite its minority status and tiny budget, and the process of getting to that dominance is all just details. You can tell that this is the case by the way that leaders in the research community are willing to become scientific advisers or host collaborative SENS research programs in their laboratories. Note the signing statement on the SENS Research Foundation advisory board page – it is in essence a refutation of much of what has been dominant in aging research for the past twenty years or so, and important figures in the research community now stand by that view:

Unfortunately, the regenerative medicine approach to combating aging is not yet being adequately pursued by major funding bodies: only a small number of laboratories worldwide are funded (either publicly or privately) to develop therapies that could rejuvenate aged but otherwise undamaged tissues. SRF has risen to the challenge of filling this void in the biomedical research funding arena.

As and when it is developed, this panel of therapies may provide many years, even decades, of additional youthful life to countless millions of people. Those extra years will be free of all age-related diseases, as well as the frailty and susceptibility to infections and falls that the elderly also experience. The alleviation of suffering that will result, and the resulting economic benefits of maintained productivity of the population, are almost incalculable. In our capacity as the overseers of SRF’s research strategy, we urge you to do all you can to help SENS Research Foundation carry out this mission with maximum speed.

Once a critical mass of the movers and shakers in a field agree with you, then the rest is history. It might be a lot of work, but it will happen. The latest figure to join the SRF scientific board is a very well known name in the life science community:

SRF’s Research Advisory Board Welcomes Dr. George Church

We are honored to welcome Dr. George Church as the newest member of SENS Research Foundation’s Research Advisory Board. Our RAB plays a key role in our mission to change the way the world researches and treats age-related disease. By applying expertise from multiple relevant areas, the Board assures that efforts and resources are directed along the most promising avenues.

Dr. Church brings relevant expertise in a number of fields, genetics in particular. He is Professor of Genetics at Harvard Medical School and Director of PersonalGenomes.org, in addition to being the author of the book, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves. His 1984 Harvard PhD included the first methods for direct genome sequencing, molecular multiplexing & barcoding, which led to the first commercial genome sequence in 1994.

His innovations in “next generation” genome sequencing and synthesis & cell/tissue engineering resulted in 12 companies spanning fields including medical genomics and synthetic biology as well as new privacy, biosafety & biosecurity policies. He is director of the NIH Center for Excellence in Genomic Science, and his honors include election to NAS & NAE and Franklin Bower Laureate for Achievement in Science.

So on the whole, things are going well, conforming to a progression that will lead to the SENS approach to aging – i.e. build the means of rejuvenation, and do it soon – becoming a large and important force in the medical research community of tomorrow. That is something of a necessary platform to build up the odds of receiving large-scale funding through the usual channels, rather than requiring visionary philanthropists and the crowdfunding efforts of interested communities to open the way.

It is still the case that one small, wealthy group could accelerate that progression by twenty years at this point by funding SENS to the tune of a few hundred million dollars. The odds of the necessary networking happening to create that event will continue to rise with progress in persuading the research community and existing constellation of funding institutions. Life is worth more than money, so the motivation to back rejuvenation research is strong, but people with access to large amounts of money tend to be very conservative in how they deploy it; only the most mainstream of initiatives can hope to be on the inside track for philanthropy. People like Peter Thiel or Dmitry Itskov are not commonplace, sadly.

Source:
http://www.fightaging.org/archives/2013/03/the-sens-research-foundation-is-forging-ahead.php

Source:
http://www.longevitymedicine.tv/the-sens-research-foundation-is-forging-ahead/

Via Newswise: "Why all the attention on TOR? TOR (target of rapamycin) is a key nutrient-sensing catalytic enzyme that evolution has conserved among every plant and animal species that has cells containing a nucleus. TOR mediates the connection between nutrients in the environment to the growth and metabolism of the organism. Studies in flies, worms, yeast and mice support the notion that the TOR signaling network also plays a pivotal role in regulating the aging process. When TOR signaling is reduced, either through genetic manipulation or via the use of drugs, the organism presumes there are reduced nutrients in its environment and goes into a 'survival' mode similar to that seen in dietary restriction, which has been shown to extend lifespan and slow the onset of certain age-related diseases. ... it remains to be seen which downstream effectors of TOR are key drivers of longevity and which ones elicit only minor effects. In addition to simply extending lifespan, research on the protective effects of TOR is likely to identify which age-related diseases can be slowed by inhibition of the TOR pathway."

View the Article Under Discussion: http://www.newswise.com/articles/tor-a-key-mediator-of-the-effects-of-dietary-restriction-and-its-impact-on-aging

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Every year something on the order of 50 million people die, and the fine structure of the brain that houses their minds is allowed to decay, destroying them forever. It does not have to be this way: the technology exists to plastinate and store the newly deceased, preserving the data of the mind until such time as medical technology can work a restoration. "The Open Letter on Brain Preservation seeks to raise awareness regarding the science, ethics and legality surrounding the emerging scientific process of chemical, whole-brain preservation. ... We, the undersigned, hereby publicly profess our human right to undergo a high-quality elective chemical brain preservation procedure immediately upon our physical death, and demand that such a procedure be made legal and accessible within the existing medical system in our countries of residence. We further demand that if medical evidence exists that an individual's brain is being substantially damaged by Alzheimer's, tumors, or other disease processes that elective brain preservation be available prior to that individual's natural death."

View the Article Under Discussion: http://brainpreservation.org/index.php?path=letter

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

A position paper by Aubrey de Grey, a number of other important biogerontologists, and folk from the LifeStar Institute: "The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people." This more or less reflects the LifeStar Institute position, complementary with that of the SENS Foundation, but with more of an organizational focus.

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20630854

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

CNN Money is running a longer piece on calorie restriction mimetic research and the goal of slowing down aging to extend healthy life: "In early 1934, Depression-weary Americans were beginning to see tendrils of hope poking out of the bleak landscape. ... But one of the new year's most promising developments passed almost unnoticed. ... researcher Clive McCay was nearing the end of a four-year study that showed that rats' life spans were greatly extended when they were put on near-starvation diets. To many of his scientific peers, McCay's data made no sense at all. A glorious new chapter in nutrition science had been opened not long before by the discovery of dietary deficiencies behind scourges such as rickets, pellagra, and beriberi. In the wake of such progress, it seemed almost subversive to suggest that a bunch of rodent Oliver Twists, raised on such short rations that their growth was stunted, could live radically longer than well-fed ones. ... Over the next several decades, his discovery was all but forgotten outside of the back halls of science - a laboratory curiosity that didn't actually spark much curiosity. Most scientists were reluctant to risk wasting time probing an anomaly that seemed as baffling as aging itself. Calorie restriction (CR), as it's now called, eventually was shown to extend many species' life spans by a third or more. Now that anti-aging research is hot, it seems bizarre that CR spent decades on science's back shelf."

View the Article Under Discussion: http://money.cnn.com/2010/05/24/retirement/retire_rich_anti_aging.fortune/

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Building medical technologies to repair and reverse degenerative aging is one part of a much broader set of transhumanist ideals: aging is only one of many current limits on the human condition that we can work to transcend through applied technology. It is a very important one, far and away the most important one in my opinion, but still one among many. Transhumanism exists as a named brand of thought and vision that some see as being separate from simple common sense about technology (i.e. use it to make things better) because we are moving, quite rapidly, from an age in which we could only crudely change ourselves into an age where the sky is the limit in terms of changing our biology and our minds. To some eyes there is a line in the sand somewhere past our present medical technology and somewhere before being able to regrow limbs, reverse aging, or build artificial intelligences.

Yet I think we’ve all seen that line shift ever forward as medicine and other technologies advance. Yesterday’s uproar over any specific biotechnology is today’s acceptance (take stem cell research as a recent line item, for example). It is a grand flaw in the human condition that people fight so much against all that is new, even while taking full advantage of the benefits provided by everything their parents fought against. It’s dumb behavior. It slows things down – and in the case of finding ways to treat and ultimately cure degenerative aging, that has a staggering cost in lives and suffering.

With the publicity for a new book on transhumanist thought, I noticed a couple of interviews and articles emerge from the community in recent days. A few links follow, starting with some thoughts on opposition to transhumanist goals. These follow much the same script as opposition to the idea of extending healthy human life; a whole lot of misconceptions and a bunch of stubborn, misplaced idealism.

Common Misconceptions about Transhumanism

Asserting that only death can give life meaning is another bizarre contradiction, and, moreover, a claim that life can have no intrinsic value or meaning qua life. It is sad indeed to think that some people do not see how they could enjoy life, pursue goals, and accumulate values in the absence of the imminent threat of their own oblivion. Clearly, this is a sign of a lack of creativity and appreciation for the wonderful fact that we are alive. I [refute] the premise that death gives motivation and a “sense of urgency” and make the opposite case – that indefinite longevity spurs people to action by making it possible to attain vast benefits over longer timeframes. Indefinite life extension would enable people to consider the longer-term consequences of their actions. On the other hand, in the status quo, death serves as the great de-motivator of meaningful human endeavors.

Humanity and Transcendence

Futurists Samantha Atkins and PJ Manney join Phil and Stephen to discuss whether there is anything truly new in the movement known as “transhumanism.” Was there ever a time when humanity wasn’t striving to transcend its current state?
Perhaps we’ll find that we have always lived in the future. If so – how is the situation any different today?

An Interview With David Pearce

David Pearce is a British utilitarian philosopher. He believes and promotes the idea that there exists a strong ethical imperative for humans to work towards the abolition of suffering in all sentient life. His book-length internet manifesto The Hedonistic Imperative outlines how technologies such as genetic engineering, nanotechnology, pharmacology, and neurosurgery could potentially converge to eliminate all forms of unpleasant experience among human and non-human animals, replacing suffering with gradients of well-being, a project he refers to as “paradise engineering”.

I have a great deal of sympathy for the Hedonistic Imperative viewpoint. I think that it’s importance and relevance to the cultural mainstream will grow alongside progress in the technological capacity to alter the operation of the human brain – though of course it really should be one of the motivations driving a great deal of that progress, the other being the urge to reverse neurodegeneration and sustain the biological infrastructure of the human mind in good health indefinitely.

Source:
http://www.fightaging.org/archives/2013/03/interviews-and-commentary-from-the-transhumanist-community.php

Source:
http://www.longevitymedicine.tv/interviews-and-commentary-from-the-transhumanist-community/

The liver is one of the few organs capable of significant regeneration in humans – but even this is more a case of compensatory growth than true regeneration of the sort seen in lower animals. Still, there is probably value in finding out how and why this happens in the liver and not in other organs:

[Researchers have] identified a protein complex that acts as a molecular switch turning on a self-regeneration program in the liver. The protein complex furthermore fine tunes liver metabolism, allowing this to run efficiently in parallel with the tissue damage repair. The new knowledge challenges the current focus on stem cells and may point towards future simplification of treatments used for repairing tissue damage.

“Our new data challenge the predominant ‘stem cell-mania’ as the results reveal important molecular mechanisms that enable ordinary liver cells to divide and repair tissue damage. This may point to ways of using ordinary liver cells for therapeutic purposes, as these cells may be easier to use than stem cells.”

Tissue renewal [is] a job for the stem cells present in our body. One exception is the specialised cells of the liver called hepatocytes. They are responsible for the metabolic functions of the liver, but can at the same time produce new liver cells. “Our results show how a protein complex is changed upon damage to the liver, making it function as a ‘switch’ turning on a self-renewal program in the hepatocytes. The protein complex literally turns on selected genes that enable division of the hepatocytes, while maintaining their metabolic functions.”

The extraordinary ability of the liver cells to divide almost indefinitely resembles the ability of stem cells to self-renew and this finding challenges the current focus on stem cells and stem cell therapy. The new results [are] consistent with new studies of self-renewal in the group of white blood cells called macrophages. “We see a clear overlap in the molecular mechanisms controlling self-renewal in hepatocytes and macrophages and that could indicate the existence of a more general self-renewal program used by specialised cell types. If this is the case, it can really change the current perception that only stem cells are responsible for renewal of our tissues.”

Link: http://news.ku.dk/all_news/2013/2013.3/self-repair_of_liver_damage/

Source:
http://www.fightaging.org/archives/2013/03/investigating-the-mechanisms-of-liver-regrowth.php

Source:
http://www.longevitymedicine.tv/investigating-the-mechanisms-of-liver-regrowth/

One of the root causes of aging is the formation of advanced glycation end-products (AGEs), something that happens much faster in a diabetic metabolism, but which nonetheless happens to all of us and causes progressively greater harm as the years pass. AGEs gum together and disable vital protein machinery, and also hammer on cell receptors in ways that cause chronic inflammation and other ills.

Past work on ways to break down AGEs – AGE-breaker drugs – largely occurred prior to the present rapid pace of development in biotechnology, and was both laborious and ultimately of little use in people despite promising animal studies. It turned out that the most important types of AGE in long-lived humans are not the same as in short-lived rodents, and thus drugs that help rats do little for people. However, one single form of human AGE – glucosepane – does make up the vast, overwhelming majority of AGEs in tissues such as skin. So it is a very viable, narrow target now that the research community knows enough to identify it as the primary target.

A safe way to remove glucosepane is needed in order to largely eliminate this contribution to degenerative aging. Sadly, as for much of the foundations of future rejuvenation therapies, little work and funding is directed to this end. This is thus one of the areas in which the SENS Research Foundation hopes to step in and spur greater interest and progress. Here are some notes on the current research programs funded by the Foundation to this end:

Chemical “crosslinking” of the structural proteins of our arteries slowly stiffens them with age, leading to more rigid blood vessels, rising “systolic” blood pressure (the first or top number in a blood pressure reading), and eventually to the loss of the ability of the kidneys to filter toxins from our blood, and a rising risk of stroke with age. Rejuvenation biotechnology can prevent these scourges at their source. New medicines that break apart these molecular “handcuffs” would allow the proteins of the arteries could move freely again, restoring the supple flexibility and cushioning capacity of aging arteries to youthful health and functionality. As a result, damage to the kidneys would be prevented, and strokes averted.

With a generous donation from software entrepreneur Jason Hope, SENS Research Foundation and the Cambridge University Institute of Biotechnology have established a new SENS Research Foundation Laboratory at Cambridge. With no one else taking on this challenging, critical research, the scientists in the Cambridge SENS lab will initiate work on biomedical solutions to glucosepane crosslinks starting from the ground up – with research to develop reagents that can rapidly and specifically detect proteins that have been crosslinked by glucosepane. The development of such reagents is an indispensible enabling technology for the development and testing of candidate glucosepane-breaking drugs.

In parallel, SENS Research Foundation is also providing funding to Dr. David Spiegel’s group at Yale University, which has special expertise in making glycation crosslinks and which has recently been studying the mechanisms and chemical vulnerabilities of precursors of glucosepane. Dr. Spiegel’s group has also recently published a report clarifying how the first generation crosslink-breaking drug worked. Once the Cambridge SRF lab has successfully established methods for identifying proteins that have been handcuffed together by glucosepane, Dr. Spiegel’s group will use them to begin developing potential glucosepane-cleaving agents. Completing the cycle, candidate agents can then be tested at the Cambridge center – initially in tissue culture, and eventually in vivo.

Once developed, any glucosepane-labeling reagents that emerge from the first phase of this work will made available as openly as possible, to accelerate research into the role of crosslinks in disease and aging, and into ways to combat them.

Link: http://www.sens.org/research/research-blog/project-break-aging-arteries-free

Source:
http://www.fightaging.org/archives/2013/03/sens-research-foundations-age-breaker-research-programs.php

Source:
http://www.longevitymedicine.tv/sens-research-foundations-age-breaker-research-programs/

“The best stem cell meeting in the
world” is underway today in San Francisco – conducted at taxpayer
expense – but the public is barred from attending.

 “The purpose of meeting is to bring together investigators funded
by CIRM, to highlight their research, and encourage scientific
exchange and collaboration.”

Source:
http://feedproxy.google.com/~r/blogspot/uqpFc/~3/uiwodYaNIP8/public-banned-from-best-stem-cell.html

Source:
http://www.longevitymedicine.tv/public-banned-from-best-stem-cell-meeting-in-the-world/

Mitochondrial damage is important in aging, and a range of evidence suggests it to be perhaps the most important contribution to aging. You might look at the membrane pacemaker theory of aging for example, which points to differences in susceptibility to mitochondrial damage between similar species with divergent life spans, where greater damage resistance correlates to longer life spans.

Mitochondria damage themselves quite readily in the course of the normal operations. They generate the fuel used by other cellular processes, and in the course of doing so also create a flurry of oxidizing compounds – free radicals – that can react with and harm protein machinery. There are natural antioxidant compounds localized to the mitochondria that slow this process down by getting to the free radicals first. Researchers have shown that life span in mice can be extended by boosting the presence of some of these compounds.

It works the other way too; removing or mutating SOD1, one of these antioxidants, shortens mouse life span. Here is an interesting demonstration showing that calorie restriction reverses this effect. That suggests that, while researchers have shown that the benefits of calorie restriction depend on the cellular recycling process of autophagy in some species, the primary mode of operation might be to alter mitochondrial function. Perhaps this occurs through an enhanced autophagic recycling of damaged mitochondria, but other mechanisms are possible:

Dietary restriction is a powerful aging intervention that extends the life span of diverse biological species ranging from yeast to invertebrates to mammals, and it has been argued that the anti-aging action of dietary restriction occurs through reduced oxidative stress/damage. Using Sod1-/- mice, which have previously been shown to have increased levels of oxidative stress associated with a shorter life span and a high incidence of neoplasia, we were able to test directly the ability of dietary restriction to reverse an aging phenotype due to increased oxidative stress/damage.

We found that dietary restriction increased the life span of Sod1-/- mice 30%, returning it to that of wild type, control mice fed ad libitum. Oxidative damage in Sod1-/- mice was markedly reduced by dietary restriction. Analysis of end of life pathology showed that dietary restriction significantly reduced the overall incidence of pathological lesions in the Sod1-/- mice fed the dietary restricted-diet compared to Sod1-/- mice fed ad libitum, including the incidence of lymphoma (27 vs 5%) and overall liver pathology. In addition to reduced incidence of overall and liver specific pathology, the burden and severity of both neoplastic and non-neoplastic lesions was also significantly reduced in the Sod1-/- mice fed the dietary restricted-diet.

These data demonstrate that dietary restriction can significantly attenuate the accelerated aging phenotype observed in Sod1-/- mice that arises from increased oxidative stress/damage.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23459073

Source:
http://www.fightaging.org/archives/2013/03/suggesting-that-calorie-restriction-primarily-operates-on-mitochondrial-function.php

Source:
http://www.longevitymedicine.tv/suggesting-that-calorie-restriction-primarily-operates-on-mitochondrial-function/

http://www.youtube.com/watch?v=Iw5fl0qt3_c

Porter County Old Jail Museum Celebrates Christmas
This is the opening day of the Christmas season held on the First Friday in December at the Porter County Jail in conjunction with the Holly Days Live Nativity. It's been an annual Festival for as long as we can remember. There's live chorus singing, horse driven wagon rides, train rides for the kids, and live entertainment at the Central Park Stage. The 2013 Alzheimer's Walk is May 18th, 2013. #65279; Keenan will be returning for a repeat performance. contact the Community Relations Coordinator Alzheimer's Dementia Services of Northern Indiana 219-789-2470

By: Susie Baxter<span style="color: #666666; font-size: 11px;"

Original post:
Porter County Old Jail Museum Celebrates Christmas – Video

Source:
http://www.longevitymedicine.tv/porter-county-old-jail-museum-celebrates-christmas-video/

http://www.youtube.com/watch?v=WE6-XUkq2D4

Hornet and Loads of Gigs (feat. Riot dudes)
Went to London with Matt and Rob of Riot Underground to see Hornet at the Barfly on 28 Feb. Great show! Also I've got a bunch of shows coming up this month–hope to see you on the road somewhere: UPCOMING GIGS 13 March with RIOT UNDERGROUND. Fahrenheit 55, Guildford. (acoustic) 15 March with HOLLYWOOD TRASH “Sordid 'n' Immoral” EP Release show. Talking Heads, Southampton. 16 March with HOLLYWOOD TRASH “Sordid 'n' Immoral” tour. The Chase, Market Rasen. 17 March with HOLLYWOOD TRASH “Sordid 'n' Immoral” tour. Golden Diamond, Sutton in Ashfield. 18 March with HOLLYWOOD TRASH “Sordid 'n' Immoral” tour. The Boileroom, Guildford. 21 March with RIOT UNDERGROUND supporting White Pigeon's album release of “Property of White Pigeon” with Rough Cut. The Star, Guildford. 22 March with HOLLYWOOD TRASH “Sordid 'n' Immoral” tour. The Duke, Neath (Wales). 23 March with HOLLYWOOD TRASH Dementia Awareness Festival, Scruffy Murphys, Birmingham. 24 March with HOLLYWOOD TRASH “Sordid 'n' Immoral” tour. The Crown, Littlehampton. 30 March with RIOT UNDERGROUND pub gig at The Great Western, Basingstoke. Website: adriennecowan.com Facebook: http://www.facebook.com Twitter: twitter.com Riot Underground: http://www.facebook.com Hollywood Trash: http://www.facebook.com

By: Adrienne Cowan<span style="color: #666666; font-size: 11px;"

Read more:
Hornet and Loads of Gigs (feat. Riot dudes) – Video

Source:
http://www.longevitymedicine.tv/hornet-and-loads-of-gigs-feat-riot-dudes-video/

http://www.youtube.com/watch?v=YzYBoBff7vU

#9733; Dead Space 3 Playthrough – Part 13 – Cradle Ops w/ iHamster
#9733; Dead Space 3 – Part 13 #9660; In this episode of Dead Space, I try to match up shapes, go for a ride in a lift and throw spiky arms at monsters. Later I run for my life. Oh dear. __________Director__________ Youtube: goo.gl Twitter: goo.gl __________________________ #9658; Dead Space 3 #9660; Dead Space 3 is a third-person shooter survival horror video game, developed by Visceral Games and published by Electronic Arts. Dead Space 3 pits player character Isaac Clarke against the Necromorphs, human corpses reanimated by the signal of an alien artefact known as the Marker. The Resource Integration Gear suit returns, using holographic displays projected from the players' suit and weapons to display health and ammo count, respectively. In vacuum areas a timer will appear on the player's right shoulder, indicating how much oxygen that character has left before they suffocate. Dead Space 3 has a drop-in/drop-out online co-op mode for its campaign. Sergeant John Carver is the playable co-op character. Each player will have alternate experiences as a result of their characters' dementia Release Date #10140; February 5, 2013 Genre #10140; Survival horror, third-person shooter Publisher #10140; Electronic Arts Developer #10140; Visceral Games Platforms #10140; Microsoft Windows, PlayStation 3, Xbox 360 #9658; Click “Like” and “Favorite” if you like this video. Helps us make more! Tell us what you think in the comments below #9660;

By: iHamsterGears<span style="color: #666666; font-size: 11px;"

Go here to see the original:
★ Dead Space 3 Playthrough – Part 13 – Cradle Ops w/ iHamster – Video

Source:
http://www.longevitymedicine.tv/a%CB%9C-dead-space-3-playthrough-part-13-cradle-ops-w-ihamster-video/