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Longevity Meme Newsletter, May 25 2009

LONGEVITY MEME NEWSLETTER
May 25 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.

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CONTENTS

- Curing Cancer: Easy or Hard?
- Persuasion Beyond the Scientific Community
- Exercise Reduces Mitochondrial DNA Damage
- Discussion
- Latest Healthy Life Extension Headlines

CURING CANCER: EASY OR HARD?

Within the next few years, I expect to see much stronger indications from ongoing research as to just how hard it will be to defeat cancer. Defeating cancer is, of course, very necessary as a step along the road to greatly extending healthy life:

https://www.fightaging.org/archives/2009/05/do-broad-commonalities-exist-in-cancer.php

"Let me explain what I mean by 'easy.' This is an era in which we can order cells around, identify cells by tiny differences in their surface biochemistry, construct viruses to order, and in which researchers are rapidly deciphering and manipulating the most fundamental mechanisms of our biology. In this sort of background, 'easy' means that researchers find some common mechanism necessary to all (or even just most) cancers. Scientists will then pile in and develop a way of attacking cancer by disrupting or manipulating that mechanism.

"'Hard' on the other hand means that there is no common mechanism shared between more than a tiny fraction of cancers ... Right now, the dominant thinking in the cancer research community is that cancer is hard. Everyone would like to see a breakthrough that makes it easy, however. You can see some of this at work in cancer stem cell research in past years. Are these errant stem cells distinctive in any way across some or all cancers, and so a single type of therapy can be deployed for many cancers, or are they as varied as cancers are in all other ways? Are cancer stem cells a path to 'easy' or are they just another facet of 'hard?'"

PERSUASION BEYOND THE SCIENTIFIC COMMUNITY

I believe that growing public support for longevity research is very necessary if we are going to make significant progress in the decades ahead, as research and development follows public opinion on longer timescales. But let's play devil's advocate on this point for a change:

https://www.fightaging.org/archives/2009/05/to-what-extent-is-persuasion-required-beyond-the-scientific-community.php

"The people who will be performing the necessary work to repair and reverse aging are life scientists and the halo of technicians surrounding that core research community. Those scientists also set the stage for the range of projects likely to be approved by funding organizations through education (both direct and indirect), the nature of their grant proposals, and so forth: they are the arbiters of truth when it comes to what is possible. ... So, the argument goes, if you persuade a significant community of life scientists to talk about and be interested in working on aspects of engineered longevity, everyone outside the scientific community will come around to support that work. ... Start with the scientists and others will follow."

EXERCISE REDUCES MITOCHONDRIAL DNA DAMAGE

As you all no doubt know by now, damage to the vulnerable DNA contained within mitochondria, the power plants of your cells, is an important contribution to the degenerations of aging:

https://www.fightaging.org/archives/2006/10/how-age-damaged-mitochondria-cause-your-cells-to-damage-you.php

Here's a look at how exercise seems to somewhat improve the situation, in muscle tissue at least:

https://www.fightaging.org/archives/2009/05/exercise-versus-mitochondrial-dna-damage.php

"It has been shown that resistance-exercise training increases muscle strength and function in older adults, in association with a reduction in markers of oxidative stress and an improvement in mitochondrial function."

The level of mitochondrial DNA damage is reduced in the exercising folk, though the researchers are not sure as to the mechanism by which this happens. It may be that exercise stimulates less damaged satellite progenitor cells to clean house, or it may be that exercise stimulates the process of autophagy, causing the muscle cells themselves to recycle more of the damaged mitochondria they carry.

However it turns out, we can't exercise our way to agelessness, however. Studies suggest that an extra decade, give or take, is the plausible difference in life expectancy between regular exercise and a sedentary life style. While exercise and calorie restriction both appear to slow most (even near all) of the effects of aging, far better technologies aimed at repairing the damage rather than slowing its accumulation are both possible and needed.

DISCUSSION

The highlights and headlines from the past week follow below.

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

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LATEST HEALTHY LIFE EXTENSION HEADLINES

Early Stem Stem Cell Therapy for Kidney Disease (May 22 2009)
https://www.fightaging.org/archives/2009/05/early-stem-stem-cell-therapy-for-kidney-disease/
The Times of India reports on early results in using stem cells to repair nephritis: Indian researchers claim "to have pioneered stem cell therapy for the first time on patients suffering from acute and chronic nephritis which may end in kidney failure. Nephritis is an early kidney disease which in many cases is chronic and becomes resistant to drugs. The disease may lead to kidney failure. Since we are doing stem cell therapy for kidney transplant patients, we decided we should also try using it to prevent kidney failure as well ... The stem cell therapy for nephritis has been done in two patients. ... The bone marrow and mesenchymal stem cells were delivered directly into the kidneys through [an artery] so as to help the organ repair the damage. ... This treatment is at experimental stage as we are still working out the dose of stem cells per kg that a patient may need for best results." Both patients greatly improved, to be point of being able to claim a cure, but as noted this is very early stage work. Still, India is not the US; while its regulators are excessive, they are nowhere near as bad as the FDA. So expect to see medical tourism for this therapy within the next year or two.

Hypoxic Response and Calorie Restriction (May 22 2009)
https://www.fightaging.org/archives/2009/05/hypoxic-response-and-calorie-restriction/
The hypoxic response (the way in which cells respond to low oxygen levels) can be beneficially manipulated to produce a number of positive results, such as triggering cells to work harder to remove a buildup of damaging biochemicals. Now it seems that this signaling system is also involved in calorie restriction, and may be the cause of some fraction of the resulting health and longevity benefits: "HIF-1 (hypoxia-inducible factor 1) [helps] cells survive by 'turning on' when oxygen levels are low. ... [scientists] have shown that HIF-1 is also a key player in dietary restriction. HIF-1 is involved in a molecular pathway known to regulate cell growth and metabolism in response to nutrients and growth factors. ... the molecular mechanisms involved in how dietary restriction slows cancer and extends lifespan have been largely unknown. ... This study gets us closer to understanding that process and gives us better targets for both designing and testing drugs which could mimic the effects of dietary restriction in humans ... The research involved nematode worms that were genetically altered to both under and over-express HIF-1. The animals, which are the most-often used model to study aging, were fed different diets. Animals that were designed to over-express HIF-1 did not get the benefit of lifespan extension even though their diets were restricted. Animals that under-expressed HIF-1 lived longer, even when they had a nutrient-rich diet."

More on Parkinson's Disease as Autophagy Failure (May 21 2009)
https://www.fightaging.org/archives/2009/05/more-on-parkinsons-disease-as-autophagy-failure/
You might recall a comparatively recent synthesis of Parkinson's research into a complete view of how the condition kills vital neurons. Here's more along those lines: alpha-synuclein (ASYN) "is an abundant neuronal protein closely linked to Parkinson's Disease (PD) pathogenesis ... The mechanisms through which [ASYN] leads to neuronal death in Parkinson's disease (PD) are uncertain. In isolated liver lysosomes, mutant ASYNs impair Chaperone Mediated Autophagy (CMA), a targeted lysosomal degradation pathway; however, whether this occurs in a cellular context, and whether it mediates ASYN toxicity, is unknown." The authors go on to show that yes, alpha-synuclein does disrupt autophagy - which means that cells will eventually die due to accumulating waste they cannot remove. This is, in effect, an unfortunate and very localized acceleration of one of the known causes of aging: a build-up of unwanted biochemical detritus inside our cells. Whatever the outcome for Parkinson's disease, we would all benefit from therapies capable of removing biochemical junk that our cells cannot deal with themselves.

Making Sense of Gene Expression Patterns and Aging (May 21 2009)
https://www.fightaging.org/archives/2009/05/making-sense-of-gene-expression-patterns-and-aging/
Gene expression, the process by which the body manufactures the protein components of molecular machinery and control mechanisms, changes constantly. Some proteins are turned out in greater quantities, some less. This should be an ongoing record of the changes that happen with aging, and therefore also helpful on the path to slowing, preventing, and reversing aging. If we can make any sense of the complexity, that is: "To study how gene changes are related to individual longevity, we need another type of data in addition to gene expression profiles: the survival time of individual animals after their gene expression is measured. With this information, we could determine which transcriptional responses are associated with a longer lifespan, and in principle even develop a personalized medicine approach to aging: we could train a machine learning algorithm to peek at the expression levels of a handful of crucial genes and predict your physiological age - and the number of healthy years you have left. Previous [studies] of aging humans haven't included survival times because we live too long. Recently, some human survival data - together with matching gene expression data from lymphoblastoid cell lines - have become available from a long-range study that began in the early 1980s. In the first aging study to take advantage of this resource, [researchers] mine the data to identify gene changes associated with longevity."

More Data Pointing to the Importance of Mitochondria (May 20 2009)
https://www.fightaging.org/archives/2009/05/more-data-pointing-to-the-importance-of-mitochondria/
Here a research group digs into a common factor observed as a result of a number of different longevity mutations in nematode worms: lower mitochondrial membrane potential, implying increased mitochondrial uncoupling, a process by which mitochondria produce heat rather than chemical energy for the cells. As we already know, greater uncoupling is correlated with greater longevity. "[Mitochondrial] energy production via oxidative phosphorylation generates a mitochondrial membrane potential (DeltaPsim) across the inner membrane. In this work, we show that a lower DeltaPsim is associated with increased lifespan in [nematode worms]. The long-lived mutants daf-2, age-1, clk-1, isp-1 and eat-2 all have a lower DeltaPsim than wild type animals. ... We conclude that longevity pathways converge on the mitochondria and lead to a decreased DeltaPsim. Our results are consistent with the 'uncoupling to survive' hypothesis, which states that dissipation of the DeltaPsim will extend lifespan." Mitochondria are very important to longevity; all the signs point in that direction.

Stem Cells Targeting Cancer (May 20 2009)
https://www.fightaging.org/archives/2009/05/stem-cells-targeting-cancer/
Targeted therapies are the immediate future of cancer treatments: destroy only the cells that matter with few or no side-effects. Here, stem cells are used as the targeting mechanism: "Experiments in cell cultures and in mice showed the adult stem cells - a type known as mesenchymal stem cells - could home in on cancer cells and deliver a lethal protein that attacked only the cancer while sparing normal healthy tissue. ... We've developed cells which specifically target cancer through the body and deliver an anti-cancer protein to where it is needed in a seek-and-destroy approach ... [researchers] altered the cells to express or make the cancer-killing protein called TNF-related apoptosis-inducing ligand or TRAIL. ... This protein has the ability to cause the death only of cancer cells. By combining these two approaches, we have a cell which has the ability to go around the body and find and destroy tumors. ... An attractive property of these cells is that they are 'immunoprivileged,' meaning the body will not reject them as foreign invaders. That means they can be made in batches instead of having to make custom stem cell treatments for each patient ... the team hopes human trials could begin in two or three years."

Automation of Skin Tissue Engineering (May 19 2009)
https://www.fightaging.org/archives/2009/05/automation-of-skin-tissue-engineering/
Automation makes products and processes much less expensive, so it's only a matter of time and ingenuity before it's broadly applied to tissue engineering, as noted in this press release: "artificial skin is rare. [The] production is complex and involves a great deal of manual work. At this time, even the market's established international companies cannot produce more than 2,000 tiny skinpieces a month. ... In a multi-stage process, first small pieces of skin are sterilized. Then they are cut into small pieces, modified with specific enzymes, and isolated into two cell fractions, which are then propagated separately on cell culture surfaces. The next step in the process combines the two cell types into a two-layer model, with collagen added to the cells that are to form the flexible lower layer, or dermis. This gives the tissue natural elasticity. In a humid incubator kept at body temperature, it takes the cell fractions less than three weeks to grow together and form a finished skin model with a diameter of roughly one centimeter. The technique has already proven its use in practice, but until now it has been too expensive and complicated for mass production."

The Baltimore Longitudinal Study of Aging (May 19 2009)
https://www.fightaging.org/archives/2009/05/the-baltimore-longitudinal-study-of-aging/
A general interest article on one of the longest-running human studies from the Washington Post: "Every year hundreds of people travel to Baltimore for an unusual purpose. ... these folks, some of whom have made this journey for decades, believe the trip is worth their time and expense because how they live - calculated according to everything from the strength of their grip to how many apples they consume in a month - may offer clues to how the rest of us might live better, longer, healthier lives. These individuals [are] participants in the Baltimore Longitudinal Study of Aging (BLSA), the country's longest-running study of aging. Since 1958, a total of more than 1,400 volunteers have agreed to regularly undergo in-depth physicals and memory and other screenings conducted by the study's physicians. The resulting data span more than half a century and are a gold mine for researchers interested in the aging process. Because of the BLSA, scientists know that signs indicating that a person could be at risk for dementia and other cognitive diseases may appear 20 years before symptoms emerge. Findings that today are common knowledge (that exercise can help reduce high blood pressure, for one) can be traced back to BLSA's annual physicals and the data analysis done by the study's scientists. Think of it as a vast historical record."

Calorie Restriction in Primates (May 18 2009)
https://www.fightaging.org/archives/2009/05/calorie-restriction-in-primates/
An academic video from the University of Wisconsin: "Ricki Colman, PhD, reviews the long-term health benefits of caloric restriction (CR) using data from a 20 year study in non-human primates at the Wisconsin National Primate Research Center. She outlines positive health changes associated with longevity including lower diabetes incidence, less age-associated loss of muscle mass, altered energy expenditures, and lower rates of obesity." The human studies show much the same, aside from the longevity implications that have yet to be measured well. That said, there is at least some evidence from the analysis of past studies that calorie restriction contributes to human longevity - but it's nowhere near as solid as the results demonstrated in mice and other lesser species. The evidence for significant health benefits in humans through calorie restriction is, however, very solid. No presently available medical technology even comes close to generating the level of health benefits obtained through eating fewer calories while still obtaining optimal nutrition - which is a state of affairs we'd all like to change.

mTOR and Osteoporosis (May 18 2009)
https://www.fightaging.org/archives/2009/05/mtor-and-osteoporosis/
From EurekAlert!: "In osteoporosis, excessive bone resorption occurs. The bones lose their density and are therefore prone to breakage. Even minor falls can lead to serious bone fractures. The interplay between two cell types determines bone density: bone forming cells (osteoblasts) and bone resorbing cells (osteoclasts). The equilibrium between these two cell types is strictly regulated to prevent the formation of either too much or too little bone. ... LAP is the term researchers use to denote the full-length isoform of [the gene] C/EBPbeta, and LIP is the term for the short isoform. LAP activates another gene switch [which] suppresses the formation of bone resorbing osteoclasts. In contrast, LIP, suppresses this gene switch and thus enhances the proliferation and activity of the osteoclasts. As a result, the osteoclasts resorb more bone substance than is built by the osteoblasts. The researchers suspect that imbalance in the ratio between LAP and LIP plays a role in osteoporosis. The activity of a signaling molecule – mTOR – determines which of the two isoforms LAP and LIP is formed. ... it may be possible to develop new drugs that regulate the activity of mTOR and, thus, remedy the disturbance in osteoclast function." mTOR activity, you might recall, is altered by the practice of calorie restriction.

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