I first noticed the Russia 2045 initiative late last year, and remarked on it as a contrasting approach to achieving agelessness. A diversity of initiatives is a good thing in any field of human endeavor:

To my eyes, the most interesting aspect of this Russia 2045 initiative is that, unlike any other serious proposal I'm aware of, their focus is on getting out of biology and into machine bodies as rapidly as possible. ... In essence, this is a course to throw away as much of the body as possible as soon as possible - a path based on a different set of preconceptions about difficulty and efficiency on the road leading to an artificial brain hosting a once-biological human mind. If aiming for life spans of thousands of years, this is the exactly same place we'll get to in the end even if we start out by maintaining our biological bodies and brains for as long as possible through rejuvenation biotechnologies.

In essence the Russia 2045 strategy swaps most of the challenges and research goals of rejuvenation biotechnology for a different set of challenges and research goals regarding brain-machine interfaces, supporting the brain outside the body, and maintaining the brain against aging while doing it. Whether this makes for an easier problem space is very open to debate.

But on with the more recent news: there was a Global Future 2045 conference last month, organized by the same group:

"Global Future 2045" is a nonprofit organization with the goal of creating a network community with the world's leading scientists in the field of life extension and to support them as an investment hub, contributing to various projects.

You should peruse the presentation videos, as they give a fair idea as to the focus: to transcend biology as rapidly as possible, and outline the details of that path in much the same spirit as the SENS platform discusses how to retain one's biology in good working condition for as long as desired.

A Wired article provides a little more background on this organization and its backer:

Dmitry Itskov, a 31-year-old Russian media mogul, [has] a massive, sci-fi-esque venture of his own ... Itskov's plan: Construct robots that'll (within 10 years, he hopes) actually store a human's mind and keep that consciousness working. Forever. "This project is leading down the road to immortality," Itskov, who founded New Media Stars, a Russian company that runs several online news outlets, tells Danger Room. "A person with a perfect Avatar will be able to remain part of society. People don't want to die."

...

Until now, most of the work on Itskov's Avatar has taken place in Russia, where he claims to have hired 30 researchers - all of them paid out of his own deep pockets. Now, Itskov plans to take the mission global. "I want to collaborate with scientists from around the world," he says. "This is a new strategy for the future; for humanity."

As a technology program that requires a great deal of research, this project will succeed for the long term only if it expands out into the broader scientific community: relationships built, knowledge exchanged, interest spurred. Pointed, narrow-focus programs within well-funded small groups can achieve their milestones, but they cannot build enough to change the world without large numbers of other participants joining in, competing, filling in the gaps, and building on top of the foundations. This is true of all ventures that aim that high - if the first step is vision, and the second step obtaining resources, then the last is persuasion.

In any case, I look forward to seeing how this develops. The world needs more earnest, vocal people out to build their slice of the science fiction future and persuade as many others as will listen.

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

We are far from the first generation to have looked at the state of science and postulated that we can significantly extend human life span through some specific means - but we are the first generation to have possession of the necessary scientific knowledge to be correct in our evaluation. That we have this knowledge is why you can't just look at the long history of predictions of longevity and say "we're just another generation that will be disappointed - it's all more of the same." The past is a great place to look if you want to predict the future of politics, but a terrible resource for predicting the future of technology. There is an enormous difference between the state of life science of today and the nascent biotechnology of the 1970s and advocates like Timothy Leary - and not to mention the science of the early 20th century as is referenced in this article: "It might seem as if a magic [longevity-enhancing] pill isn't so far off. But before we get too cheery about the prospects for these discoveries, it's useful to be reminded of the many longevity 'breakthroughs' that have come and gone in the past. One such potential advance was hailed in the November 1929 issue of Technology Review, in an essay called 'Forestalling Death: The Cow's Contribution to Human Longevity' ... In the previous 125 years, Tobey observed, average life span had risen from the low 30s to the upper 50s. This was primarily due to reductions in infectious disease and in the infant death rate ... It wasn't enough to simply reduce a threat such as infectious disease - it was imperative that we find something we could add to our lives, or maybe simply increase our intake of something we were already consuming. He felt recent research might have uncovered just such a substance. ... He pointed to recent experiments at Columbia University, wherein one set of rats had been given an 'adequate diet' of one-sixth dried whole milk and five-sixths whole wheat. An 'optimal diet' group, meanwhile, received double the milk and less wheat. The average duration of life was almost exactly ten percent greater in those subjects receiving the optimal diet ... Is it possible that we have had the fountain of youth within our grasp throughout the ages that man has been seeking this liquid phantasm? Milk has always been recognized as the one most nearly perfect food ... but apparently it possesses hitherto undreamed of virtues." And so on: the end result is more of the oral fixation that seems to so dominate our culture - in the popular imagination everything of significance must be something that we put in our mouths and consume. Most important medicine, of course, is nothing of the sort.

Link: http://www.technologyreview.com/biomedicine/39630/

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

Another potential method to treat or minimize the progession of sarcopenia: researchers "report that a family of protein transcription factors, called 'Forkhead (Fox0)' plays a significant role in the regulation of skeletal muscle mass. Specifically, they found that interfering with the activity of these transcription factors prevents muscle wasting associated with cancer and sepsis, and even promotes muscle growth. This discovery is likely to be relevant to any disease, condition or lifestyle that leads to muscle wasting, including voluntary inactivity. [Researchers] genetically inhibited the activity of 'Forkhead boxO' proteins, or 'FoxO,' in the skeletal muscle of healthy control mice, septic mice, and mice with cancer. The loss of muscle mass in those with cancer and sepsis was significantly decreased by inhibition of FoxO activity. In healthy control animals inhibiting FoxO activity caused an increase in muscle cell size which occurred as a result of protein synthesis. ... FoxO proteins may provide a target for therapies aimed at reducing muscle wasting and thus improving the quality of life and survival rates for patients with many different diseases."

Link: http://www.eurekalert.org/pub_releases/2012-02/foas-nwn022912.php

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

A few years ago, researchers demonstrated a way to reverse some of the effects of Alzheimer's disease - a method that, interestingly, didn't involve targeting buildup of beta amyloid, presently the mainstream focus of the Alzheimer's research community.

HDAC2 regulates the expression of a plethora of genes implicated in plasticity - the brain's ability to change in response to experience - and memory formation. ... Several HDAC inhibitors are currently in clinical trials as novel anticancer agents and may enter the pipeline for other diseases in the coming two to four years. ... The researchers conducted learning and memory tasks using transgenic mice that were induced to lose a significant number of brain cells. ... after taking HDAC inhibitors, the mice regained their long-term memories and ability to learn new tasks. In addition, mice genetically engineered to produce no HDAC2 at all exhibited enhanced memory formation.

There are a few other studies out there to place question marks next to the primacy of amyloid in Alzheimer's disease - but you have to weigh them against the huge number of studies suggesting that it is important. But it's certainly the case that, given the ability, we would want to remove all such buildups of metabolic byproducts that appear with age. Young people don't have them, old people have them, ergo they may be part of the problem - and given limited information and large resources, why not work toward reversing all changes?

Here's a recent update on HDAC2 research. To my eyes, the most promising aspect of this work is not that it will necessarily lead to a viable therapy - the odds are always low for every research program - but that it shows Alzheimer's to be a reversible disease until quite late in the game.

The researchers found that in mice with Alzheimer's symptoms, HDAC2 (but not other HDACs) is overly abundant in the hippocampus, where new memories are formed. HDAC2 was most commonly found clinging to genes involved in synaptic plasticity - the brain's ability to strengthen and weaken connections between neurons in response to new information, which is critical to forming memories. In the affected mice, those genes also had much lower levels of acetylation and expression. .. The researchers then shut off HDAC2 in the hippocampi of mice with Alzheimer's symptoms, using a molecule called short hairpin RNA, which can be designed to bind to messenger RNA - the molecule that carries genetic instructions from DNA to the rest of the cell. With HDAC2 activity reduced [genes] required for synaptic plasticity and other learning and memory processes [were] expressed. In treated mice, synaptic density was greatly increased and the mice regained normal cognitive function.

...

The researchers also analyzed postmortem brains of Alzheimer's patients and found elevated levels of HDAC2 in the hippocampus and entorhinal cortex, which play important roles in memory storage.

...

The findings may explain why drugs that clear beta-amyloid proteins from the brains of Alzheimer's patients have offered only modest, if any, improvements in clinical trials ... The new study shows that beta amyloid also stimulates production of HDAC2, possibly initiating the blockade of learning and memory genes. ... We think that once this epigenetic blockade of gene expression is in place, clearing beta amyloid may not be sufficient to restore the active configuration of the chromatin.

Which all sounds to me very much like real progress in understanding the mechanics of Alzheimer's, if it's all validated by the research community - incremental, true, but progress nonetheless.

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

A few years ago, researchers demonstrated a way to reverse some of the effects of Alzheimer's disease - a method that, interestingly, didn't involve targeting buildup of beta amyloid, presently the mainstream focus of the Alzheimer's research community.

HDAC2 regulates the expression of a plethora of genes implicated in plasticity - the brain's ability to change in response to experience - and memory formation. ... Several HDAC inhibitors are currently in clinical trials as novel anticancer agents and may enter the pipeline for other diseases in the coming two to four years. ... The researchers conducted learning and memory tasks using transgenic mice that were induced to lose a significant number of brain cells. ... after taking HDAC inhibitors, the mice regained their long-term memories and ability to learn new tasks. In addition, mice genetically engineered to produce no HDAC2 at all exhibited enhanced memory formation.

There are a few other studies out there to place question marks next to the primacy of amyloid in Alzheimer's disease - but you have to weigh them against the huge number of studies suggesting that it is important. But it's certainly the case that, given the ability, we would want to remove all such buildups of metabolic byproducts that appear with age. Young people don't have them, old people have them, ergo they may be part of the problem - and given limited information and large resources, why not work toward reversing all changes?

Here's a recent update on HDAC2 research. To my eyes, the most promising aspect of this work is not that it will necessarily lead to a viable therapy - the odds are always low for every research program - but that it shows Alzheimer's to be a reversible disease until quite late in the game.

The researchers found that in mice with Alzheimer's symptoms, HDAC2 (but not other HDACs) is overly abundant in the hippocampus, where new memories are formed. HDAC2 was most commonly found clinging to genes involved in synaptic plasticity - the brain's ability to strengthen and weaken connections between neurons in response to new information, which is critical to forming memories. In the affected mice, those genes also had much lower levels of acetylation and expression. .. The researchers then shut off HDAC2 in the hippocampi of mice with Alzheimer's symptoms, using a molecule called short hairpin RNA, which can be designed to bind to messenger RNA - the molecule that carries genetic instructions from DNA to the rest of the cell. With HDAC2 activity reduced [genes] required for synaptic plasticity and other learning and memory processes [were] expressed. In treated mice, synaptic density was greatly increased and the mice regained normal cognitive function.

...

The researchers also analyzed postmortem brains of Alzheimer's patients and found elevated levels of HDAC2 in the hippocampus and entorhinal cortex, which play important roles in memory storage.

...

The findings may explain why drugs that clear beta-amyloid proteins from the brains of Alzheimer's patients have offered only modest, if any, improvements in clinical trials ... The new study shows that beta amyloid also stimulates production of HDAC2, possibly initiating the blockade of learning and memory genes. ... We think that once this epigenetic blockade of gene expression is in place, clearing beta amyloid may not be sufficient to restore the active configuration of the chromatin.

Which all sounds to me very much like real progress in understanding the mechanics of Alzheimer's, if it's all validated by the research community - incremental, true, but progress nonetheless.

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

A mere 40% extension of life span in nematode worms via a novel method is a part of the general background noise of aging research nowadays: "The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to [longevity-enhancing genes]. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor."

Link: http://dx.doi.org/10.1371/journal.pone.0032183

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

The core point of SENS, the Strategies for Engineered Negligible Senescence, is explained in this short interview: "Could you elaborate on the idea mentioned on SENS: that it isn't necessary to know, from an 'engineering' perspective, everything about the degenerative processes that occur at the cellular level in order to treat aging in the way you envision? ... The basic point we're making there is to contrast the regenerative approach with the more traditional idea of trying to make metabolism create molecular and cellular damage more slowly. In order to do the latter, we would need to understand our biology massively better than we do at present, so as to avoid creating unforeseen side-effects. By contrast, with the regenerative approach we don't need to know much about how damage comes about: it's enough just to characterize the damage itself, so as to figure out ways to repair it. We're effectively sidestepping our ignorance of metabolism. ... Rejuvenation biotechnologies are simply regenerative therapies that pre-empt the diseases and disabilities of old age. They consist of molecular, cellular or whole-organ interventions that restore the structure of the target to something like how it was in early adulthood. This includes a variety of stem cell therapies, and also tissue engineering to create artificial organs. At SENS Foundation we don't work much on those types of therapy, because they're being very capably pursued elsewhere; rather, we focus on the more neglected but equally vital components of this 'divide-and-conquer' approach to combating aging. For example, we have a large project aimed at eliminating 'molecular garbage' from cells - indigestible material whose accumulation leads to diseases like atherosclerosis and macular degeneration - by introducing non-human enzymes to augment the body's natural ability to break down unwanted by-products of metabolism."

Link: http://www.themanitoban.com/2012/02/live-longer-and-prosper/9213/

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

The INDY gene in fruit flies was one of the earlier discoveries in the genetics of longevity. The initials of the name stand for I'm Not Dead Yet, an allusion to a Monty Python scene and one of many unusual names given to fly genes. You'll find a range of posts on INDY back in the Fight Aging! archives, following the research highlights over the years.

Here is an open access review paper that provides an introduction the INDY and the present state of knowledge regarding its operation when mutated to extend fly life span:

Single gene mutations that extend life span are important tools for discovering pathways underlying aging. Of particular interest have been mutations in genes that are conserved across diverse species, since they suggest common mechanisms for aging regulation. For instance, mutations in insulin signaling genes affect the life span of yeast, worms, fruit flies, and mice ... Mutations in the Indy (I'm Not Dead Yet) gene dramatically extend the life span of the fruit fly, Drosophila melanogaster. Indy encodes the fly homolog of a mammalian di and tricarboxylate transporter involved in regulating plasma and liver levels of citrate and other Krebs cycle intermediates.

...

Reduced expression of fly Indy or two of the C. elegans Indy homologs leads to an increase in life span. Fly and worm tissues that play key roles in intermediary metabolism are also the places where Indy genes are expressed. One of the mouse homologs of Indy (mIndy) is mainly expressed in the liver. It has been hypothesized that decreased INDY activity creates a state similar to caloric restriction (CR). This hypothesis is supported by the physiological similarities between Indy mutant flies on high calorie food and control flies on CR.

...

Flies, worms, and mice show similar physiological changes when INDY expression is reduced, suggesting an evolutionarily conserved role for INDY in the regulation of metabolism. ... The studies on mice further suggest protection from metabolic syndrome and insulin resistance, whether the causative factors are diet or age. INDY is thus an attractive drug target for the amelioration of metabolic disorders associated with diet or advanced age, separate from any effects on longevity.

This is one amongst many longevity-related genes, with likely many more yet to come. There is no shortage of opportunity for research groups wanting to work on the slow and incremental side of the road to the future of human longevity - to produce old-style drugs that change the long term operation of metabolism. The opportunities are there, but this is far from the best path to extending healthy human life spans.

As regular readers know, there is another path forward - the SENS vision of biotechnologies based on repair of damage rather than slowing down the rate of damage. This is likely to be no more costly [and] yet will produce at the end of the day a true cure for aging, not just a marginal benefit and a couple of extra years of life.

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

The INDY gene in fruit flies was one of the earlier discoveries in the genetics of longevity. The initials of the name stand for I'm Not Dead Yet, an allusion to a Monty Python scene and one of many unusual names given to fly genes. You'll find a range of posts on INDY back in the Fight Aging! archives, following the research highlights over the years.

Here is an open access review paper that provides an introduction the INDY and the present state of knowledge regarding its operation when mutated to extend fly life span:

Single gene mutations that extend life span are important tools for discovering pathways underlying aging. Of particular interest have been mutations in genes that are conserved across diverse species, since they suggest common mechanisms for aging regulation. For instance, mutations in insulin signaling genes affect the life span of yeast, worms, fruit flies, and mice ... Mutations in the Indy (I'm Not Dead Yet) gene dramatically extend the life span of the fruit fly, Drosophila melanogaster. Indy encodes the fly homolog of a mammalian di and tricarboxylate transporter involved in regulating plasma and liver levels of citrate and other Krebs cycle intermediates.

...

Reduced expression of fly Indy or two of the C. elegans Indy homologs leads to an increase in life span. Fly and worm tissues that play key roles in intermediary metabolism are also the places where Indy genes are expressed. One of the mouse homologs of Indy (mIndy) is mainly expressed in the liver. It has been hypothesized that decreased INDY activity creates a state similar to caloric restriction (CR). This hypothesis is supported by the physiological similarities between Indy mutant flies on high calorie food and control flies on CR.

...

Flies, worms, and mice show similar physiological changes when INDY expression is reduced, suggesting an evolutionarily conserved role for INDY in the regulation of metabolism. ... The studies on mice further suggest protection from metabolic syndrome and insulin resistance, whether the causative factors are diet or age. INDY is thus an attractive drug target for the amelioration of metabolic disorders associated with diet or advanced age, separate from any effects on longevity.

This is one amongst many longevity-related genes, with likely many more yet to come. There is no shortage of opportunity for research groups wanting to work on the slow and incremental side of the road to the future of human longevity - to produce old-style drugs that change the long term operation of metabolism. The opportunities are there, but this is far from the best path to extending healthy human life spans.

As regular readers know, there is another path forward - the SENS vision of biotechnologies based on repair of damage rather than slowing down the rate of damage. This is likely to be no more costly [and] yet will produce at the end of the day a true cure for aging, not just a marginal benefit and a couple of extra years of life.

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