Longevity Meme Newsletter, May 11 2009
LONGEVITY MEME NEWSLETTER
May 11 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
- Bypassing Age-Related Mitochondrial Damage
- Microfunding of Early Stage Scientific Research
- Preventing New Medicine
- Discussion
- Latest Healthy Life Extension Headlines
BYPASSING AGE-RELATED MITOCHONDRIAL DAMAGE
Mitochondria are your power plants, toiling away inside your cells to turn food into the chemical ATP that is used as fuel to power cellular processes. As the years pass, however, mitochondria accumulate damage in ways that harm their cell, eventually causing it to spew forth biochemical pollution into the surrounding tissue. The growing number of these polluting cells and the harm they cause is one of the root causes of aging. See here for a more detailed explanation:
A number of groups have worked on ways to solve this problem in past years, such as by replacing mitochondria entirely, replacing the critical damaged portions, or moving the most important biochemical machinery of mitochondria into a backup location where it can't be damaged. You'll find a summary of some of that work in progress in the following post from the archives:
https://www.fightaging.org/archives/2008/01/targeting-mitochondria.php
My attention was recently drawn to another potential method to at least partially address age-related mitochondrial damage and dysfunction, this time by importing a gene present in some species but lacking in insects and mammals:
https://www.fightaging.org/archives/2009/05/bypassing-oxphos-damage.php
"Mitochondria [have] several methods of turning food into ATP, the chemical used as fuel by your cells. The primary method is OXPHOS, but this generates free radicals that can sometimes so damage a mitochondrion that it can no longer run the OXPHOS process. It then switches to a secondary (and less efficient) process that has two effects: a) the mitochondrion becomes far less likely to be recycled along with other worn cellular components, so eventually only damaged mitochondria are left in a cell, and b) enough of these damaged mitochondria bring their cell into a state of imbalance that can only be solved by dumping large quantities of free radicals into the surrounding tissue. That in turn causes all sorts of wide-ranging damage to the body's biochemistry, building up over time.
"The key gene [in essence] acts as a bypass for blockages in the so-called oxidative phosphorylation (OXPHOS) [process] in mitochondria. [Researchers liken OXPHOS] to a series of waterfalls in a hydroelectric power station. Only, in the case of mitochondria, it is electrons that flow to release energy that is captured in molecular form [as ATP].
"This is the first [test] for the idea that you can take a gene that encodes a single polypeptide and bypass OXPHOS where it is blocked [due to damage]. You may lose power from one [of the waterfalls in the OXPHOS system] but power from the others can be restored. With a single peptide, you can bypass two-thirds of the system. That's the beauty of the idea."
MICROFUNDING OF EARLY-STAGE SCIENTIFIC RESEARCH
A few thoughts on funding of important research:
https://www.fightaging.org/archives/2009/05/microfunding-of-earlystage-scientific-research.php
"Why do people give five figure charitable contributions to cause-focused intermediaries (e.g. a cancer non-profit, or the SENS Foundation) rather than find early stage, important projects they would like to fund themselves? I don't think we can blame that on complexity or lack of knowledge, given that angel investors looking at for-profit startups are in exactly the same position of ignorance regarding the vast range of potential projects to invest in and the huge complexities of their industries.
"No. I think it's the infrastructure - or rather the lack of infrastructure surrounding early stage scientific research. The web of relationships, technology, and eager passage of information that enables a dynamic start-up culture is lacking for early stage research. A yawning gulf separates research communities from the many purses that might be opened were the connection made. People donate to research via intermediary organizations with broad goals because there is no readily available, widely understood way to do anything else.
"As we move into the second decade of this most interesting century, the cost of answering questions and producing important new results in scientific research will continue to fall. The breadth of important, game-changing work that could be accomplished by a post-grad in a few months - already much larger than people think - will increase. There is a tremendous, growing incentive to open up the whole early stage funding situation for far greater transparency and outreach. The more that people can see exactly what they are funding, the more they will become involved."
PREVENTING NEW MEDICINE
We live in an age of tremendous potential to generate benefits through biotechnology - yet are stuck with regulatory environments that seem designed to do everything possible to stop that potential dead in its tracks:
"Regulatory bodies like the FDA have every incentive to stop the release of new medicine: the government employees involved suffer far more from bad press for an approved medical technology than they do from the largely unexamined consequences of heavy regulation. These consequences go far beyond the obvious and announced disapproval of specific medical technologies: the far greater cost lies in all the research, innovation and development that was never undertaken because regulatory burdens ensure there would be no profit for the developer. Personal gain for the regulator is thus to destroy the gains of people they will never meet, the exact opposite of what occurs in an open marketplace.
"A good example of this downward spiral in action is formed by the FDA and pharmaceutical industry in the US. The FDA continues to ratchet up the cost of producing new medical technology to the point at which progress is slowed to a crawl. The short term cost incurred by a politician in blocking advances is far less than that accrued by allowing advances to proceed. The pharmaceutical industry uses the FDA as a weapon to protect itself from progress in the form of competition, disruptive new technologies, and other endeavors that will greatly help health and longevity."
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
Harming Yourself Bad For Longevity (May 08 2009)
https://www.fightaging.org/archives/2009/05/harming-yourself-bad-for-longevity/
We can all knowingly look at the smokers, but how often have you thought about what else you might be doing or failing to do that is known to greatly impact life expectancy? From EurekAlert!: "Non-smokers live longer and have less cardiovascular disease than those who smoke, according to a 30-year follow-up study of 54,000 men and women in Norway. ... deaths were recorded by linkage to the Norwegian population registry and, between 2006 and 2008, those surviving responded to a follow-up questionnaire. This allowed division of the participants according to their smoking status - never-smokers, ex-smokers, current smokers of 1-9 cigarettes a day, 10-19 cigarettes a day and more than 20 cigarettes a day (the last group referred to as 'heavy smokers'). Results showed that, from the original 54,075 participants, 13,103 had died by the time of follow-up. But it was a significant finding that, of these, 45% of the heavy-smoking men had died during the 30 years, compared to just 18% of the never-smokers. Similarly, 33% of the heavy-smoking women had died, but only 13% of the never-smokers. ... These results show what a tremendous impact smoking has on mortality. We are talking about very high numbers of people." Now recall that failing to exercise has roughly the same impact on life expectancy as smoking.
Dietary Substitution and Longevity (May 08 2009)
https://www.fightaging.org/archives/2009/05/dietary-substitution-and-longevity/
This is interesting, though I have to wonder how it will interact with the findings relating to methionine and calorie restriction in higher animals. Researchers have shown "that yeast cells maintained on a glycerol [rather than glucose] diet live twice as long as normal - as long as yeast cells on a severe caloric-restriction diet. They are also more resistant to cell damage. ... genetically engineered long-lived yeast cells that survive up to 5-fold longer than normal have increased levels of the genes that produce glycerol. In fact, they convert virtually all the glucose and ethanol into glycerol. ... When the researchers blocked the genes that produce glycerol, the cells lost most of their life span advantage. ... [Researchers] believe that the 'glucose to glycerol' switch represents only a component of the protective systems required for the extended survival. ... This is a fundamental observation in a very simple system, that at least introduces the possibility that you don't have to be calorie-restricted to achieve some of the remarkable protective effects of the hypocaloric diet observed in many organisms, including humans. It may be sufficient to substitute the carbon source and possibly other macronutrients with nutrients that do not promote the 'pro-aging' changes induced by sugars."
Methionine Restriction Differs From Calorie Restriction (May 07 2009)
https://www.fightaging.org/archives/2009/05/methionine-restriction-differs-from-calorie-restriction/
While methionine restriction brings similar longevity and health benefits to calorie restriction where it has been tested, it doesn't appear to be quite the same thing under the hood - probably meaning the calorie restriction operates through additional mechanisms beyond a reduction in methionine intake: "Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver [biochemistry, including gene expression patterns] that are not observed in liver from age-matched Meth-R mice. These results [suggest] that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways." This is also a helpful reminder that starting calorie restriction later in life isn't a waste, and can still provide significant health benefits.
A Snapshot of Work in Targeted Nanoparticles (May 07 2009)
https://www.fightaging.org/archives/2009/05/a-snapshot-of-work-in-targeted-nanoparticles/
Being able to safely destroy or reprogram very specific cell populations will enable a wide range of very useful therapies. Here's an example of what's going on in the labs these days: researchers "have developed the basis for a four-in-one agent that can detect, target, and disable tumor cells while also making them [visible]. ... their work involves magnetic iron oxide particles with a fluorescence dye, RNA fragments, and a special peptide attached. The peptide is present to specifically identify the cancer cells; the RNA fragments suppress the special cancer-cell genes, killing the cells. The magnetic particles act as a contrast agent for magnetic resonance imaging, and the fluorescence dye allows for microscopic imaging of the target cells. ... mRNA is a good point of attack to stop the synthesis of proteins required for tumor growth. To achieve this, siRNAs (small interfering RNAs) are introduced into the cell. ... When bound to nanoparticles, the siRNAs are easier to slip into cells. In order to specifically target cancer cells, the particles carry a short peptide, called RGD, which points the way: RGD strongly binds to an integrin, a membrane protein that is anchored to metastasizing tumor cells in much higher amounts than in healthy tissue. The integrins with RGD-equipped nanoparticles are actively brought into the cell interior with their cargo intact."
How Reversible is Alzheimer's? (May 06 2009)
https://www.fightaging.org/archives/2009/05/how-reversible-is-alzheimers/
Some evidence suggests that the worst effects of Alzheimer's disease can be repaired - that memories are not destroyed, but rather become inaccessible. Researchers have "pinpointed the exact gene responsible for a 2007 breakthrough in which mice with symptoms of Alzheimer's disease regained long-term memories and the ability to learn. ... 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. The fact that long-term memories can be recovered by elevated histone acetylation supports the idea that apparent memory 'loss' is really a reflection of inaccessible memories ... These findings are in line with a phenomenon known as 'fluctuating memories,' in which demented patients experience temporary periods of apparent clarity."
A Little Methuselah Foundation Coverage (May 06 2009)
https://www.fightaging.org/archives/2009/05/a-little-methuselah-foundation-coverage/
Video at KTLA: "There's no escaping the inevitable...all of us and our loved ones will grow old. But now a cutting edge group is doing something about aging. At the southern California offices of Methuselah Foundation, KTLA has met a man who says we can live as long as our scientific imaginations allow. Methuselah Foundation creative director Roger Holzberg says it's simple: together let's aggressively attack the diseases of aging! ... Over the last century, the extent of a healthy life span has increased dramatically as we started to conquer illnesses like polio. and there is no reason why the diseases of aging can't fall like polio did, over the next decade," Holzberg says. The work of the Foundation operates on several levels: first, there's short-term care through their web site, offering 'tips for life.' Another level in the battle against aging is the 'M Prize' - it's a huge cash prize the Foundation is offering, to anyone who can best prolong life in lab animals. The 'prize strategy' is working. Already one of the entrants has helped lab mice live well beyond their years."
On Atherosclerotic Plaques (May 05 2009)
https://www.fightaging.org/archives/2009/05/on-atherosclerotic-plaques/
One important contribution to the buildup of atherosclerotic plaques and eventually atheromas is the damaged lipids generated by age-related damage to your mitochondria. Here, researchers look at what happens further down the line when the plaques become dangerous: "some 2 percent of all plaques [will] eventually lead to the development of an acute blood clot and to heart attack, sudden death, or stroke. ... The billion dollar question is why 98 percent cause no problem, and 2 percent do. ... Their report adds support to the notion that so-called endoplasmic reticulum (ER) stress together with the body's natural way of coping with that stress is one answer. ... In the case of atherosclerosis, ER stress within plaques could lead to the massive death of cells - and of macrophages in particular - leading to the generation of a structure called the 'necrotic core.' Those necrotic cores are known to be a defining feature of plaques that are vulnerable to rupture and blood clot formation." The researchers show that mice lacking the cell death response to ER stress suffer half the number of blood clots. As always, however, a much better solution would be to regularly clear the plaques rather than tinker with fundamental cell mechanisms to try and make the plaques less dangerous.
Growing More Natural Killer Cells (May 05 2009)
https://www.fightaging.org/archives/2009/05/growing-more-natural-killer-cells/
If we could introduce a very large number of active immune cells into the body for a short while, far more than the body generates by itself, we could solve a lot of problems - such as cancer. Here, a research team "demonstrated natural killer cells [derived] from human embryonic stem cells are better at killing human leukemia in mice, preventing the cancer from metastasizing in any of the animal's organs. The study has also shown stem cell-derived tumor-killing cells are highly effective in killing breast cancer, prostate cancer, testicular cancer and brain tumor cells. ... We've now proven that these cells are much more potent and effective at killing tumor cells than those coming from other sources like human umbilical cord blood, and we've been able to identify some of the reasons why. ... the next goal is to produce enough of the cells to treat humans, rather than mice. ... Based on the history of cell-based therapies at the university, I see this as very feasible. But it will take time based on the resources available to get to the scale of human treatments." You might also recall the similar GIFT immune therapy that produced very impressive results, but is presently buried beneath FDA regulatory requirements - as is all the most promising new biomedical technology.
Longevity Begets Longevity (To Some Degree) (May 04 2009)
https://www.fightaging.org/archives/2009/05/longevity-begets-longevity-to-some-degree/
Unsuprisingly, women who can give birth later in life tend to live longer - unsurprising at least from a reliability theory viewpoint of aging as accumulated damage. If you can have a child later in life, you are most likely less damaged than your peers, and therefore more likely to live longer. "Women who have babies naturally in their 40s or 50s tend to live longer than other women. Now, a new study shows their brothers also live longer, but the brothers' wives do not, suggesting the same genes prolong lifespan and female fertility, and may be more important than social and environmental factors. ... Women who had 'late fertility' - a birth at age 45 or older - were 14 percent to 17 percent less likely to die during any year after age 50 than women who did not deliver a child after age 40. That confirmed earlier studies. But those studies did not determine if the women gave birth later and lived longer because of genes or because of social and environmental factors such as good nutrition or healthy living. ... The study didn't address how much longevity is due to genetics, [but] scientists believe genes account for up to 25 percent of differences in longevity." The real lesson to take away from this is that the majority of factors influencing your longevity are not genetic and therefore under your control.
Gold Nanorods Versus Cancer (May 04 2009)
https://www.fightaging.org/archives/2009/05/gold-nanorods-versus-cancer/
A good example of more straightforward nanoengineering taking place in cancer research laboratories from ScienceDaily: "tumors in mice that received an intravenous injection of nanorods plus near-infrared laser treatment disappeared within 15 days. Those mice survived for three months with no evidence of reoccurrence, until the end of the study, while mice that received no treatment or only the nanorods or laser, did not. Once the nanorods are injected, they disperse uniformly throughout the bloodstream. Bhatia's team developed a polymer coating for the particles that allows them to survive in the bloodstream longer than any other gold nanoparticles (the half-life is greater than 17 hours). In designing the particles, the researchers took advantage of the fact that blood vessels located near tumors have tiny pores just large enough for the nanorods to enter. Nanorods accumulate in the tumors, and within three days, the liver and spleen clear any that don't reach the tumor. During a single exposure to a near-infrared laser, the nanorods heat up to 70 degree Celsius, hot enough to kill tumor cells. Additionally, heating them to a lower temperature weakens tumor cells enough to enhance the effectiveness of existing chemotherapy treatments, raising the possibility of using the nanorods as a supplement to those treatments."
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