The Science for Life Extension Foundation helped organize the 2nd International conference on the Genetics of Aging and Longevity, held back in April in Moscow. Thanks to the Foundation staff, video from the conference is starting to make its way to a YouTube channel. Here are a couple of the videos already posted; you might want to keep an open eye for others as they arrive.

Dr. Bartke reported the first evidence that mutation of a single gene can significantly extend lifespan in a mammal, and [has] extensively characterized the phenotype of long-lived Ames dwarf mice, identifying several mechanisms that are likely to explain or contribute to their delayed aging and greatly prolonged longevity.

[The] research of Dr. Reis focuses on the molecular genetics of longevity and age-associated diseases, using both previously defined mutations and gene mapping. He managed to extend the lifespan of a nematode worm, C.elegans, 10-fold by only one mutation in the age-1 gene.

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

We accumulate random nuclear DNA damage - mutations - as we age. This is understood to increase the risk of cancer, as the more mutations that occur the greater the chance that one will be of the rare type that can spawn a cancer, but there is some debate over the degree to which nuclear DNA damage contributes to aging itself. Here researchers add some more data to the picture: "Hundreds of mutations exist in leukemia cells at the time of diagnosis, but nearly all occur randomly as a part of normal aging and are not related to cancer, new research shows. [Researchers] have found that even in healthy people, stem cells in the blood routinely accumulate new mutations over the course of a person's lifetime. And their research shows that in many cases only two or three additional genetic changes are required to transform a normal blood cell already dotted with mutations into acute myeloid leukemia (AML). ... The study is the first to investigate how often mutations typically develop in healthy stem cells in the blood. ... In recent years, [researchers] have sequenced the genomes of 200 patients with AML to try to understand the mutations at the root of the disease. Without fail, each patient's leukemia cells held hundreds of mutations, posing a conundrum for scientists, who have long believed that all the mutations in a cancer cell are likely to be important for the disease to progress. ... But we knew all of these mutations couldn't be important. It didn't make any sense to us that so many mutations were present in all the cells in the tumor. ... Every person has about 10,000 blood stem cells in their bone marrow, and the researchers found that each stem cell acquires about 10 mutations over the course of a year. By age 50, a person has accumulated nearly 500 mutations in every blood stem cell. ... Mutations are known to develop in cells as we age, but no one had any idea how many mutations occur in blood stem cells and how frequently they develop. These random, background mutations occur during cell division and are unrelated to cancer. Our DNA can tolerate a huge number of these hits without any negative consequences. But if a cancer-initiating event occurs in one of these stem cells, it captures the genetic history of that cell, including the earlier mutations, and drives leukemia to develop. ... scientists were surprised to see that the total number of mutations varied by age, not by whether a patient had leukemia. Thus, a healthy person in his 40s had just about the same number of mutations in his blood stem cells as a leukemia patient of the same age had in his cancer cells."

Link: http://www.sciencedaily.com/releases/2012/07/120719132606.htm

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

From the MIT Technology Review: "Alzheimer's patients given a drug that is already used to treat immune disorders saw their condition stabilize in a small study presented at a conference this week. Study participants were given the compound - known as intravenous Ig, or IVIg - for three years. During this period, they showed no signs of further cognitive decline or memory loss. ... All participants in the study had mild to moderate Alzheimer's disease. Only four received the optimal dose of IVIg over three years. These patients showed no decline from their baseline state in cognition, memory, daily functioning, or mood - all expected effects of the disease. Patients who initially received a placebo but were later switched to IVIg treatment declined more slowly while receiving the drug. IVIg [contains] a mixture of antibodies isolated from the pooled plasma of blood donated by healthy people. The assumption is that this blood by-product contains antibodies from the healthy donors that attack the damaged proteins in Alzheimer's patients. ... such results [should] inspire a large number of scientific studies aimed at identifying the functional ingredients in the immune mixture, so that others could potentially develop a synthetic form. ... I really do hope that it turns out to work, because then it gives a good platform to start finding out what components are in there, What is it in the IVIg - is it selective antibodies against beta-amyloid, against tau, or something else?"

Link: http://www.technologyreview.com/news/428546/study-suggests-alzheimers-disease-can-be/

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

From the MIT Technology Review: "Alzheimer's patients given a drug that is already used to treat immune disorders saw their condition stabilize in a small study presented at a conference this week. Study participants were given the compound - known as intravenous Ig, or IVIg - for three years. During this period, they showed no signs of further cognitive decline or memory loss. ... All participants in the study had mild to moderate Alzheimer's disease. Only four received the optimal dose of IVIg over three years. These patients showed no decline from their baseline state in cognition, memory, daily functioning, or mood - all expected effects of the disease. Patients who initially received a placebo but were later switched to IVIg treatment declined more slowly while receiving the drug. IVIg [contains] a mixture of antibodies isolated from the pooled plasma of blood donated by healthy people. The assumption is that this blood by-product contains antibodies from the healthy donors that attack the damaged proteins in Alzheimer's patients. ... such results [should] inspire a large number of scientific studies aimed at identifying the functional ingredients in the immune mixture, so that others could potentially develop a synthetic form. ... I really do hope that it turns out to work, because then it gives a good platform to start finding out what components are in there, What is it in the IVIg - is it selective antibodies against beta-amyloid, against tau, or something else?"

Link: http://www.technologyreview.com/news/428546/study-suggests-alzheimers-disease-can-be/

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

You'll no doubt recall the 2045 initiative backed by an enthusiastic high net worth Russian individual, which appears so far to be the opening stages of a serious long-term effort to convert a fraction of that net worth into the technologies needed for artificial, non-biological bodies capable of indefinitely supporting a human brain - and after that to move on to brain emulation and mind uploading.

I commented on this vision last year:

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.

I'm of the opinion that this is not the most optimal path towards the defeat of aging, based on my understanding of the relative difficulty of building a full-featured neural interface and life support system for the brain versus realizing rejuvenation biotechnology that can repair the biological chassis we have now - even leaving aside the issue that an uploaded or emulated copy of your mind is just a copy of you, not you. In the long run we will all be wholly artificial, of course, but it seems premature to be aiming for that now versus after the advent of molecular nanotechnology and the capacity to build functional replacements for biological components (e.g. blood cells, brain cells, and so forth) that are better than the original. It is, however, very important for the general future of engineered longevity to have a diversity of approaches, disagreement, and enthusiastic people with resources and vision. At the very least, in a world in which artificial bodies are being developed with the stated goal of preventing people from aging to death, it becomes that much easier to gather support for work on the biotechnologies that can repair the damage of aging.

In any case, the 2045 Initiative is back in the press again, and here are a couple of items:

Russian Mogul to 'Forbes' Billionaires: Limitless Lifespans Can Be Yours

First up is the development of robots that can be controlled by the human mind. After that, and ideally within 10 years, Itskov wants to develop robots that can actually host a flesh-and-blood human brain, via surgical transplant. In twenty years time, things get even more interesting: Itskov anticipates "uploading" the contents of the human brain into a robot, yielding eternal life via artificial body. By 2045, he'd like to replace those 'bots entirely - with holograms. Since February, Itskov has stayed plenty busy working on his "Avatar" plan ... With a lab of scientists reportedly already working on the program in Russia, Itskov has now branched out to the U.S, with plans to open a San Francisco office this summer and host a futurity conference - called Global Future Congress - in New York later this year.

His next step: Itskov has published an open letter to the world's richest people, urging them to back the initiative - and consider volunteering themselves as potential avatars. "I urge you to take note of the vital importance of funding scientific development in the field of cybernetic immortality and the artificial body. Such research has the potential to free you, as well as the majority of all people on our planet, from disease, old age and even death."

Billionaires: Russian Mogul Wants to Upload Your Brains Into Immortality

Earlier this year, a Russian media mogul named Dmitry Itskov formally announced his intention to disembody our conscious minds and upload them to a hologram - an avatar - by 2045. In other words he outlined a plan to achieve immortality, removing the human mind from the physical constraints presented by the biological human body. He was serious. And now, in a letter to the members of the Forbes World's Billionaire's List, he's offering up that immortality to the world's 1,266 richest people.

...

"Currently you invest in business projects that will bring you yet another billion," Itskov writes. "You also have the ability to finance the extension of your own life up to immortality. Our civilization has come very close to the creation of such technologies: it's not a science fiction fantasy. It is in your power to make sure that this goal will be achieved in your lifetime."

This last note is absolutely true with regard to the SENS vision of rejuvenation biotechnologies as well: the wealthiest people in the world have it in their grasp to build a way out of aging for everyone, given that the baseline medical technologies would probably cost in the ballpark of a billion dollars and ten years to demonstrate in laboratory animals. Yet so far, they are not showing much interest - wealth doesn't grant vision, sadly, so we should all be pleased when a high net worth visionary does turn up, even if he's not working to our own favored plan of action.

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

A commentary on testing rapamycin as a therapy for age-related macular degeneration (AMD): "Although neovascular AMD only accounts for less than 15% of the overall age-related macular degeneration, it is responsible for over 80 percent of the severe vision loss cases. ... It was reported in 2004 that rapamycin (trade name sirolimus) treatment significantly reduced the extent of neovascularization [induced] in adult mice ... In an advance online publication this year [Kolosova et al] presented exciting results that rapamycin could actually prevent AMD-like retinopathy in an aging rat model that more closely resembles human AMD pathology. They investigated the effect of rapamycin on spontaneous retinopathy in senescence- accelerated OXYS rats. OXYS rats were treated orally with either 0.1 or 0.5 mg/kg rapamycin, which was given together with food. Rapamycin was found in a dose-dependent manner to reduce the incidence and severity of retinopathy, and attenuated AMD disease progression. Some histological abnormalities associated with retinopathy were notably reduced ... significantly, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats, suggesting that it is safe."

Link: http://impactaging.com/papers/v4/n6/full/100469.html

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

Trehelose is known to be involved in yeast life span, and given in the diet can extend life in nematode worms. In animals closer to we humans, it has been show to stimulate autophagy, the collection of processes by which cells recycle damaged components and remove the unwanted build-up of metabolic byproducts. More autophagy seems to be an unqualified good, and shows up as a mechanism of action by which healthy life span is extended via calorie restriction (CR), exercise, and drugs that aim to mimic some of the biochemical changes caused by CR and exercise. This all makes sense: if damaged components are removed from cells more rapidly, they have less time to cause further damage themselves. The system as a whole is better maintained. So there is some impetus in the research community to develop the means to enhance autophagy in humans.

I noticed one small portion of that line of work today - an open access study in mice that used trehalose to stimulate greater levels of autophagy, and showed a reduction in the level of degeneration expected in their brains. Like many animal studies, the mice here were engineered to develop a form of neurodegeneration comparatively rapidly, so as to provide a model for assessment of possible treatments at a lower cost:

The accumulation of insoluble proteins is a pathological hallmark of several neurodegenerative disorders. Tauopathies are caused by the dysfunction and aggregation of tau protein and an impairment of cellular protein degradation pathways may contribute to their pathogenesis. Thus, a deficiency in autophagy can cause neurodegeneration, while activation of autophagy is protective against some proteinopathies. Little is known about the role of autophagy in animal models of human tauopathy.

In the present report, we assessed the effects of autophagy stimulation by trehalose in a transgenic mouse model of tauopathy, the human mutant P301S tau mouse ... Autophagy was activated in the brain, where the number of neurons containing tau inclusions was significantly reduced, as was the amount of insoluble tau protein. This reduction in tau aggregates was associated with improved neuronal survival in the cerebral cortex and the brainstem. We also observed a decrease of p62 protein, suggesting that it may contribute to the removal of tau inclusions. ... Our findings provide direct evidence in favour of the degradation of tau aggregates by autophagy. Activation of autophagy may be worth investigating in the context of therapies for human tauopathies.

Pleasantly, the authors paid some attention as to whether providing mice with trehalose causes inadvertent calorie restriction, something that plagues the studies of incautious researchers. The effects of calorie restriction are very strong, and if your prospective treatment happens to make the mice in your study eat less - well, those mice will usually do better than their counterparts, all other things being equal. But here:

Water consumption of the three groups (no treatment, sucrose-treated and trehalose-treated) was similar. Sucrose and trehalose had no impact on the animals' weights or coat aspects, suggesting that the health of the mice was similar among the three groups.

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

You might recall that a few years ago, researchers extended life in nematode worms by feeding them trehalose. Here, scientists link normal abundances of trehalose in yeast cells with the longevity induced by calorie restriction: "Our recent investigation of how a lifespan-extending caloric restriction (CR) diet alters the metabolic history of chronologically aging yeast suggested that their longevity is programmed by the level of metabolic capacity - including trehalose biosynthesis and degradation - that yeast cells developed prior to entry into quiescence. To investigate whether trehalose homeostasis in chronologically aging yeast may play a role in longevity extension by CR, in this study we examined how single-gene-deletion mutations affecting trehalose biosynthesis and degradation impact (1) the age-related dynamics of changes in trehalose concentration; (2) yeast chronological lifespan under CR conditions; (3) the chronology of oxidative protein damage, intracellular ROS level and protein aggregation; and (4) the timeline of thermal inactivation of a protein in heat-shocked yeast cells and its subsequent reactivation in yeast returned to low temperature. Our data imply that CR extends yeast chronological lifespan in part by altering a pattern of age-related changes in trehalose concentration. We outline a model for molecular mechanisms underlying the essential role of trehalose in defining yeast longevity by modulating protein folding, misfolding, unfolding, refolding, oxidative damage, solubility, and aggregation throughout lifespan." Trehelose stimulates autophagy in higher animals, the all-important set of mechanisms that recycle damaged cell components, so one would expect it to be beneficial there as well.

Link: http://www.frontiersin.org/Integrative_Physiology/10.3389/fphys.2012.00256/full

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

Some mitochondrial DNA lineages are objectively better than others, as demonstrated by correlations with longevity in humans. Here is a correlation with dementia risk, which might be superficially explained by a greater ability to power fuel-hungry neurons, or greater resistance to mitochondrial damage over time: "Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increase neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10-12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia and haplogroup J participants experienced a statistically significant 8-year decline in 3MS, both compared with common haplogroup H. [Other variants were] associated with a significant decline in DSST score [or] 3MS score."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22785396

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

The Methuselah Foundation formally launched the New Organ initiative earlier this year: a research and technology prize aimed at speeding up tissue engineering of replacement organs. Today the Foundation announced the New Organ 100:

Today, 3,000 people will die from organ failure, many due to the lack of replacement organs. In the U.S. alone, over 100,000 are stuck on a waiting list, and many more can't even get on a list.

We need a revolution in medicine, and we need it as soon as possible.

Regenerative medicine is coming of aging. Significant breakthroughs are beginning to happen, but the funding to move the science and technology forward remains woefully inadequate.

The Methuselah Foundation is announcing today the New Organ 100 to kickstart a visible, popular movement with a singular purpose: make regenerative medicine famous to achieve whole organ manufacturing within 10 years.

We invite you to be among the initial 100 New Organizers, the seeds of the movement who each make the same pledge: give $10 a month toward raising the New Organ Prize, and ask 10 friends and family to do the same.

The goal of the New Organ Prize is simple: to stimulate progress while demonstrating the rising demand for greater R&D funding. 100% of gifts go toward growing the prize. Every gift is matched by donors to support the New Organ Fund, which funds our operations and investments in startups advancing critical technologies, such as Organovo's 3D bioprinter and Silverstone Solutions' kidney-matching software.

Lee Downing was one of the lucky ones. When he got on the waiting list for a liver transplant, it was only 4,000 people long. After his transplant in 1988, he regained his health completely. He's been actively promoting organ donation ever since, working hard to enable others to receive the git of life that he was blessed with.

And after 24 years in the trenches, he's never felt as optimistic as he does now:

"It's pretty simple. We've tried everything, and we still haven't succeeded. I believe we need a revolutionary change in our approach to transplantation, and New Organ is it. Without it, more people are going to die, and even more people are to be added to the waiting list. The New Organ Prize, where modern medicine and state-of-the-art technology merge, may be the most significant impact we can make on the current paradigm of transplantation. It's going to safe lives."

No one has ever used a prize to build a movement for social change ... until now.

Will you join us?

The Methuselah Foundation has been steadily gearing up to focus attention on the big goals in tissue engineering for some years now. It's is worth remembering that the Foundation was one of the early investors in organ printing development company Organovo, for example - and the leaders of Organovo are prominently featured as sponsors and advocates in the New Organ 100 campaign.

If you agree with the New Organ goals - tissue engineered organs in the clinic, as fast as possible - then join in, spread the word, and donate.

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

A piece by author David Stipp gives an overview of the past few years of research into the effects of rapamycin: "The first strong evidence that a drug could slow aging in mammals came out in 2009 when scientists reported that chronically feeding doses of rapamycin to mice significantly extended their average and maximum lifespans. Yet rapamycin, a drug used to help prevent rejection of transplanted organs, causes multiple side effects in people, including elevated triglycerides and cholesterol, increasing the risk of heart disease; moderate immune suppression, perhaps increasing infection risks; and low blood platelet levels, which raises the specter of dangerous bleeding. In recent years another especially surprising and troubling side effect has come to the fore: Chronically taking large doses of rapamycin induces 'insulin insensitivity' in both rodents and humans, leading to rising blood sugar and potentially to type 2 diabetes. How do we reconcile such adverse effects with the drug's unprecedented ability to boost healthy aging and longevity, at least in mice? Some telling insights on this burning issue were recently published in two reports on rapamycin's effect on insulin and blood sugar: a mouse study that revealed a probable mechanism behind the effect and a theory paper suggesting that the purported diabetes risk has been overblown."

Link: http://www.davidstipp.com/rapamycins-anti-aging-promise-mirage-or-not/

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