Better maintenance means a longer life, as illustrated by the importance of autophagy in calorie restriction (CR). Researchers are now branching out beyond CR to find other ways of influencing metabolism to better maintain cells: "The conserved insulin-signaling pathway has drawn a significant amount of attention over the past few years as a major lifespan determining signaling network. In many systems, impairing this pathway impedes the ability of caloric restriction (CR) to enhance lifespan, suggesting that nutrient sensing is key to CR. ... the Titorenko laboratory [tested] the hypothesis that networks exist within cells that are not inducible, but act constitutively to extend the lifespan of cells regardless of nutrient availability ... [the study] presents an original screen designed to isolate molecules that further lengthen the life span of yeast under calorie restriction rather than imitating this effect. ... Among the chemical compounds identified, the authors focus on one group representing 6 bile acids compounds, the most efficient of them being lithocholic acid (LCA). Bile acids are mildly toxic oxidized derivatives of cholesterol that play important roles in lipid uptake by the intestine."

View the Article Under Discussion: http://www.impactaging.com/papers/v2/n7/full/100173.html

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

A long post from MSNBC's Cosmic Log: "The quest for immortality goes back to Adam and Eve, but now some smart people are getting serious about actually bringing it within their grasp. And they're getting more attention as well. Let's take Aubrey de Grey, for example: The British gerontologist has been beating the drum for anti-aging therapies for years. He plays a prominent role in a recently published book on the immortality quest titled 'Long for this World,' a new documentary called 'To Age or Not to Age' and a just-published commentary on the science of aging. In this week's issue of Science Translational Medicine, de Grey and nine other co-authors urge the United States and other nations to set up a Project Apollo-scale initiative to avert the coming 'global aging crisis.' The experts' prescription includes a campaign to raise the general public's awareness about lifestyle changes that can lead to longer and healthier lives; a lab-based effort to develop anti-aging medicines; and a push for new techniques to repair, restore or replace the cellular and molecular damage done by age. ... There is this misunderstanding that aging is something that just happens to you, like the weather, and cannot be influenced. The big surprise of the last decades is that, in many different animals, we can increase healthy life span in various ways."

View the Article Under Discussion: http://cosmiclog.msnbc.msn.com/_news/2010/07/15/4685717-reaching-for-immortality

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

LONGEVITY MEME NEWSLETTER
July 19 2010

The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.

To subscribe or unsubscribe from the Longevity Meme Newsletter, please visit http://www.longevitymeme.org/newsletter/

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CONTENTS

- Immortality Institute International Conference in October
- LifeStar Institute Launches New Website
- Research Forges Ahead
- Discussion
- Latest Healthy Life Extension Headlines

IMMORTALITY INSTITUTE INTERNATIONAL CONFERENCE IN OCTOBER

The Immortality Institute volunteers have put together a great line-up of speakers for their forthcoming conference in Brussels, Belgium on October 9th, including researchers Leonid Gavrilov, Michael Rose, Aubrey de Grey (of course), some of the Russians from the Science Against Aging initiative, and a range of others:

http://www.fightaging.org/archives/2010/07/immortality-institute-international-conference-october-2010-in-brussels.php

“It’s a great chance for Eurozone folk to gather and meet like-minded supporters of longevity science: there are far too few such gatherings held on that side of the pond, so make the most of this one. Many of the usual suspects from the longevity science community will be speaking or presenting, as well as a fair few faces you might not be so familiar with. Not too many of the European advocates for extended healthy life spans make it out to the US-based conferences on a regular basis, so it should be a different crowd from the circuit of the past few years.”

LIFESTAR INSTITUTE LAUNCHES NEW WEBSITE

The LifeStar Institute is a project of the Millard Foundation, a family organization whose principals decided a few years ago to throw their weight behind making rejuvenation medicine a reality.

http://www.fightaging.org/archives/2010/07/lifestar-institute-launches-new-website.php

“The Institute volunteers recently launched a new website to coincide with their call for global collaboration in longevity science … Leaders in the biology and polices of aging research at the first LifeStar Institute Global Aging Science Summit conclude the time has come to launch an ambitious global effort to keep aging generations youthful, productive, and engaged to unprecedented ages. In laboratories all over the world, using genome sciences, diets including calorie restriction, and techniques of cell science and regenerative medicine, scientists are now keeping living organisms alive and healthy for increasing lengths of time never before thought possible. The obvious question: When will medical science do the same for us?”

RESEARCH FORGES AHEAD

There is always something new and interesting happening in the life science laboratories of the world. For example, from this past week:

http://www.fightaging.org/archives/2010/07/cancer-immunotherapy-in-action.php

“Researchers at UCLA’s Jonsson Comprehensive Cancer Center created a large, well armed battalion of tumor-seeking immune system cells and watched, in real time using Positron Emission Tomography (PET), as the special forces traveled throughout the body to locate and attack dangerous melanomas. … The novelty of our work is that we were able to pack together the cancer specific T cell receptor and the PET reporter genes in a single vector and use it in mice with an intact immune system that closely resembles what we would see in real patients. We were also gladly surprised to see the targeted tumors literally melt away and disappear, underscoring the power of the combined approach of immune and gene therapy to control cancer.”

http://www.fightaging.org/archives/2010/07/analysis-of-gene-expression-and-longevity-is-forging-ahead.php

“The process of gene expression, in which a gene is used as a blueprint to construct a protein, is anything but static. Levels of gene expression for individual genes rise and fall with environmental circumstances, health, injury, and over the course of aging. It’s a tremendously complex system, with a lot of feedback loops and switches, but fortunately the cost of analyzing gene expression profiles over a whole genome is falling rapidly. It is now feasible to run hundreds of such profiles over the course of a study. At the same time the tools of analysis are starting to catch up with the amount of data being generated: researchers are able to more rapidly and effectively draw conclusions from the mountainous databases they construct. So, for example, see this study on flies, which compares groups of flies selected for their longevity versus a control group of average length lives. It demonstrates that systematically sweeping the whole genome for changes in gene expression with age is a viable way to evaluate the importance of other lines of research and find new avenues for future study.”

DISCUSSION

The highlights and headlines from the past week follow below. If you have comments for us, please do send e-mail to newsletter@longevitymeme.org

Remember – if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

Reason
reason@longevitymeme.org

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LATEST HEALTHY LIFE EXTENSION HEADLINES

THE CASE FOR LATE-LIFE INTERVENTIONS IN AGING (July 16 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4815
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.

BRAIN SIZE CORRELATES WITH SPECIES LONGEVITY (July 16 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4814
Via ScienceDaily: “Mammals with larger brains in relation to body size tend to live longer. This is the conclusion reached by researchers [after] having analysed almost 500 mammal species and obtaining new data on the relation between brain size and lifespan. … The brain size of some mammals is larger than expected for their body size. This is the case of large primates, such as chimpanzees and gorilla, and of whales, dolphins and elephants. Scientists have spent years investigating why sometimes nature favours the development of large brains given that they require much more time to reach functional maturity and use up so much energy. … the size of the brain affects lifespan regardless of the size of the body. Hyenas, for example, have a larger brain than giraffes in proportion to body size and on average live longer, although they are smaller than these herbivores. … it is possible that a longer life works in favour of a delay in reproductive cycles and this would in turn allow progenitors to invest more resources and time in caring for their offspring. This also leads to the formation of stable social groups whose members, according to the Social Intelligence Hypothesis (SIH), must deal with more cognitive demands than animals living alone, and this would be the reason for larger brains.”

A CONSERVATIVE VIEW OF LONGEVITY SCIENCE (July 15 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4813
This opinion piece is an example of the sort of viewpoint held by those who believe that metabolic manipulation to modestly slow aging is the only viable way forward in longevity science: “When I tell people that anti-aging drugs are no longer a distant prospect, they often assume I’m talking about the quest for immortality. That’s not surprising, given the buzz generated in recent years by visionaries who speculate about re-engineering the human body to last thousands of years. But actually I don’t find that far-out prospect very interesting – it bears the same relationship to serious aging science that warp-drive spaceships do to aeronautical engineering. What really grabs me are experimental advances that may impinge on the lives of people I know, maybe even mine. … the only practical, near-term way to substantially increase healthy life span today is to simultaneously lower the risk of all diseases of aging. The way we now mainly buy time – administering therapies for one progressive, old-age disease at a time when it’s too late to do much good – can’t do that. Anti-aging drugs could, and at the same time they would go a long way toward ending the ruinously costly game of diminishing returns we’re playing in geriatric medicine, as we eke out incremental gains with ever pricier palliatives. In effect, they would be preventive medicines of unprecedented scope and efficacy, drastically lowering the risk of everything from Alzheimer’s to osteoporosis to wrinkles in the way that hypertension drugs now cut heart-attack risk.”

URGING A GLOBAL COLLABORATION AGAINST AGING (July 15 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4812
From the LifeStar Institute: “Leaders in the biology and polices of aging research at the first LifeStar Institute Global Aging Science Summit conclude the time has come to launch an ambitious global effort to keep aging generations youthful, productive, and engaged to unprecedented ages. In laboratories all over the world, using genome sciences, diets including calorie restriction, and techniques of cell science and regenerative medicine, scientists are now keeping living organisms alive and healthy for increasing lengths of time never before thought possible. The obvious question: When will medical science do the same for us? … The scientific panel proposes that the United States and nations across the world create a global collaboration and launch an Apollo-like Project with the following goal: translate laboratory knowledge about the degenerative changes of aging into new kinds of medicines for humans that can prevent and repair those changes. The panel urges governments and the biomedical industry to fund three key initiatives: (1) Use public health agencies to inform citizens on how they can improve their lifestyles. (2) Develop the first genuine anti-aging medicines that are able to boost the body’s ability to maintain health (3) Develop and apply regenerative methods that can remove, replace, repair, and neutralize the cellular and molecular damage that accumulate in aging bodies and restore youthful structure and function.”

USING STEM CELLS TO BUILD TEST PLATFORMS (July 14 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4811
Here is an example of the other use for stem cells: to grow tissue that can be used to test and understand specific diseases. “Researchers are applying new stem cell technology to use skin samples to grow the brain cells thought to be responsible for the onset of Parkinson’s disease … [the] team will be gathering data from over 1,000 patients with early stage Parkinson’s disease and taking small samples of skin tissue to grow special stem cells – induced pluripotent stem cells (iPS cells). iPS cells can be generated from accessible tissue such as the skin and then used to generate specific types of cell. The researchers will use the iPS cells to grow dopamine neurons – the brain cells responsible for the production of dopamine, as it is these cells which die in patients with Parkinson’s, leading to the onset of the disease. … iPS cells provide new and exciting opportunities to grow and study dopamine neurons from patients for the first time. This technology will prove to be extremely important in diseases which affect the brain because of its relative inaccessibility – it’s far easier to get a skin sample than a brain biopsy. Once we have neurons from patients we can compare the functioning of cells taken from patients with the disease and those without to better understand why dopamine neurons die in patients with Parkinson’s.”

LEF FUNDS GRANULOCYTE CANCER THERAPY (July 14 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4810
A press release: “In a discovery that made headline news around the world, Dr. Zheng Cui, of the Wake Forest University School of Medicine, developed a colony of mice with super-charged granulocytes that successfully fight off many forms of virulent cancer. … In a surprising turn of events Dr. Cui also found that a similar cancer-killing activity is present in the granulocytes of some healthy humans. … When the Life Extension Foundation learned that this potential cancer cure was not being funded, it immediately made a $200,000 grant to fund the study at the South Florida Bone Marrow/Stem Cell Transplant Institute … This new clinical trial will test this approach in humans with advanced cancer, including metastases, who have not been helped by conventional cancer therapies. The trial has received an IND (investigational new drug) status from the Food and Drug Administration (FDA) and Institutional Review Board approval. … In January of this year, Dr. Maharaj notified the Life Extension Foundation that progress was being slowed because expected funding sources had dried up. Life Extension responded with another grant of $600,000 to further advance what could be a cure for cancer.”

THE GENETICS OF HORMESIS-INDUCED LONGEVITY (July 13 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4809
Hormesis is the process whereby suffering a little biochemical damage switches metabolism into a high-repair, damage-resistant mode, thereby extending life. Here, researchers examine changes in gene expression associated with hormesis: “Ionizing radiation generates oxidative stress, which is thought to be a major cause of aging. Although living organisms are constantly exposed to low levels of radiation, most studies examining the effect of radiation have focused on accelerated aging and diminished life span that result from high-dose radiation. On the other hand, several studies have suggested that low-dose radiation enhances the longevity of Drosophila melanogaster. Therefore, investigation of the biological effects of low-dose radiation could contribute to a more comprehensive understanding of the aging process. In this study, microarray and quantitative real time-PCR were used to measure genome-wide changes in transcript levels in low-dose irradiated fruit flies that showed enhanced longevity. In response to radiation, approximately 13% of the genome exhibited changes in gene expression, and a number of aging-related genes were significantly regulated. These data were compared with quantitative trait loci affecting life-span to identify candidate genes involved in enhanced longevity induced by low-dose radiation. This genome-wide survey revealed novel information about changes in transcript levels in low-dose irradiated flies and identified 39 new candidate genes for molecular markers of extended longevity induced by ionizing radiation. In addition, this study also suggests a mechanism by which low-dose radiation extends longevity.”

THE COST OF OBESITY (July 13 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4808
A good example of what obesity does to your long term health: “Men who enter adult life obese face a life-long doubling of the risk of dying prematurely, new research has found. In a study presented today (Tuesday) at the International Congress on Obesity in Stockholm, researchers tracked more than 5,000 military conscripts starting at the age of 20 until up to the age of 80. They found that at any given age, an obese man was twice as likely to die as a man who was not obese and that obesity at age 20 years had a constant effect on death up to 60 years later. They also found that the chance of dying early increased by 10% for each BMI point above the threshold for a healthy weight and that this persisted throughout life, with the obese dying about eight years earlier than the non-obese. … Body mass index (BMI) was measured at the average ages of 20, 35 and 46 years, and the researchers investigated that in relation to death in the next follow-up period. A total of 1,191 men had died during the follow-up period of up to 60 years. The results were adjusted to eliminate any influence on the findings from year of birth, education and smoking. … At age 70 years, 70% of the men in the comparison group and 50% of those in the obese group were still alive and we estimated that from middle age, the obese were likely to die eight years earlier than those in the comparison group.”

ON CALORIE RESTRICTION (July 12 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4807
Christopher Westphal of Sirtris is writing a series of guest columns in the Boston Globe: “Last week, I wrote that the best way to live healthier longer was to eat less and exercise more. Meticulous readers asked which of these two approaches, precisely, had more scientific support. Such questions may reflect wishful thinking: Those who exercise a lot might wonder if they can eat the equivalent of steak and fries every night. And for those who don’t want too much exercise, might they focus instead on eating less? Unfortunately for those who, like me, have modest will power at the table, the data are clear. The most robust way to increase healthy lifespan in a broad variety of organisms is in fact calorie restriction. In other words, it behooves us to cut our calorie intake markedly, while still maintaining a balanced diet that includes essential vitamins and minerals. Whether we can bring ourselves to do so is another question entirely. … Who among us, you might ask, would have the fortitude to emulate the calorie restriction studies conducted on animals? It turns out that there are at least hundreds of Americans, and many more individuals worldwide, who are severely restricting their calorie intake in the hopes of extending their healthy lifespans. Studies have indeed found that key cardiovascular measurements, such as blood pressure and heart rate, are much improved in individuals who significantly restrict their calorie intake.”

PTEN AND NERVE REGENERATION (July 12 2010)
http://www.longevitymeme.org/news/vnl.cfm?id=4806
Via EurekAlert!: “Scientists have discovered a way to enhance nerve regeneration in the peripheral nervous system. This important discovery could lead to new treatments for nerve damage caused by diabetes or traumatic injuries. Peripheral nerves connect the brain and spinal cord to the body, and without them, there is no movement or sensation. Peripheral nerve damage is common and often irreversible. … [Researchers] used a rat model to examine a pathway that helps nerves to grow and survive. Within this pathway is a molecular brake, called PTEN, that helps to prevent excessive cell growth under normal conditions. In addition to discovering for the first time that PTEN is found in the peripheral nervous system, [the team] demonstrated that following nerve injury, PTEN prevents peripheral nerves from regenerating. The team was able to block PTEN, an approach that dramatically increased nerve outgrowth. … We were amazed to see such a dramatic effect over such a short time period. No one knew that nerves in the peripheral system could regenerate in this way, nerves that can be damaged if someone has diabetes for example. This finding could eventually help people who have lost feeling or motor skills recover and live with less pain.”

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If you have comments for us, please do send email to newsletter@longevitymeme.org.

New mission for salinomycin in cancer by Cord Naujokat, SciTopics, July 15, 2010. Excerpt (in the “continue reading” section):

In addition, a very recent study demonstrates that salinomycin overcomes ATP-binding cassette (ABC) transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like cells (3).

Reference #3: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells, by Dominik Fuchs and 4 co-authors, including Cord Naujokat, Biochem Biophys Res Commun 2010(Apr 16);394(4): 1098-104 [Epub 2010(Mar 27)][PubMed citation].

Comments: Near the end of this article about salinomycin is the comment that “the investigation of its safety, toxicity, pharmacology and anticancer activity in humans will be a challenge.” The author then mentions a preliminary study of “a small cohort of patients with metastatic breast cancer or metastatic head and neck cancers“. The results of this preliminary study of the toxicity of salinomycin are summarized. They have not yet been published in the peer-reviewed literature, although a manuscript has been submitted [see reference #4 in the article]. The implication of these preliminary results is that there may be a “therapeutic window” for salinomycin, that is, a drug dosage that yields clinically significant benefits in the absence of excessive toxicity.

For a previous commentary on salinomycin, see: Cancer stem cell breakthrough by Kat Arney, Science Update blog, Cancer Research UK, August 14, 2009. Excerpt:

We need to stress that these were laboratory experiments, and there is no evidence yet that salinomycin can treat cancer in humans. Salinomycin is currently used as an antibiotic for chickens and cows, and it can be toxic or even fatal to humans, causing serious muscle and heart problems.

If there is a “therapeutic window” for salinomycin, it could be a small one, and is likely to vary from one tumor to another.

For a previous post to this blog about salinomycin, see: Identification of selective inhibitors of breast CSCs in mice, August 14, 2009.