Fight Aging!

LONGEVITY MEME NEWSLETTER
April 06 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

- Dwelling in the Past
- Amyloidosis, Killer of Centenarians
- Another Strategy for Waste Chemical Clearance
- Discussion
- Latest Healthy Life Extension Headlines

DWELLING IN THE PAST

Living with a mind focused on the recent past, looking back rather than ahead, is the natural human mode of operation. This evolved mindset served our ancestors well, but it's not so useful now that rapid change is upon us:

https://www.fightaging.org/archives/001710.php

"In the world of last week, in which nothing really changes but your age, you won't make it to 100. That's a safe bet no matter how well you take care of your health. The only thing that will enable many of us to live in good health past a century of life is the advance of medical technology - in other words, new science and new therapies that don't exist in the here and now.

"The speed with which medicine advances is predicated upon just how many of us support that advance. If you live your life in the land of last week, or the land of how your parents lived, or any of the other seductive places that your evolved nature causes you to be predisposed to enjoy, then I'm sorry to say that you're not helping. The coming decades could see some of the most transformative advances in medical technology yet, and it is possible to envisage with some precision the tools and therapies that could rejuvenate the old by repairing the damage of aging. This will only happen rapidly enough to help those of us reading this now if many more people get behind the wheel and push."

You can help push at the Methuselah Foundation:

http://www.mfoundation.org

AMLYOIDOSIS, KILLER OF CENTENARIANS

Centenarians get to be centenarians by surviving or avoiding the age-related conditions that kill the rest of us before we see our hundredth year of life. Based on present data, it seems that what eventually catches up with them is a buildup of metabolic byproducts ("amyloid") to a level that causes organ failure - a condition called amyloidosis.

We all go through life under an ever-increasing burden of amyloid and other metabolic byproducts that damage the ability of our cells, and later our organs, to do their jobs. Some fraction of aging itself results from this damage. A few well-known age-related diseases are clearly the consequences of an accelerated increase in amyloid deposits, possibly occurring because mechanisms that clean up the amyloid start to fail: Alzheimer's, for example.

Some unfortunate folk are stricken with amyloidosis comparatively early in life, possibly as a result of genetic mutation. A few research groups are progressing towards therapies that can remove the buildup of amyloid, maintaining it at non-toxic levels:

https://www.fightaging.org/archives/001712.php

"Prof Pepys has long believed that the key to understanding [amyloidosis] is a related blood protein called SAP, which sticks to amyloid fibres and stops enzymes removing them. ... a drug called CPHPC [aimed] to clear the destructive amyloid deposits from patients by removing the protective SAP from their blood. Prof Pepys was working then in collaboration with Roche. But the Swiss pharmaceutical giant eventually pulled out. ... Prof Pepys has reached an agreement with another big pharmaceutical group, UK-based GlaxoSmithKline, to collaborate on producing a treatment for amyloidosis based on the CPHPC-antibody combination."

Those of us interested in progress towards engineered longevity should follow amyloidosis research with interest. Strategies under development for dealing with specific types of amyloid deposit may turn out be more broadly applicable to future longevity therapies.

ANOTHER STRATEGY FOR WASTE CHEMICAL CLEARANCE

Along the same lines, here is another example of a strategy worth watching. For many types of damaging metabolic byproducts, biological processes already exist in our bodies that can, in theory, clear out the unwanted biochemicals that build up with age. Some researchers are working to identify ways to provoke these mechanisms into more energetic action, identify why they fail with age, or otherwise extend their capabilities:

https://www.fightaging.org/archives/001711.php

"A new study has identified a potential strategy for removing the abnormal protein that causes Huntington's disease (HD) from brain cells, which could slow the progression of the devastating neurological disorder ... One of the major challenges of research into neurodegenerative disorders like Huntington's, Alzheimer's and Parkinson's diseases - all of which involve accumulation of proteins within the brain - has been how to activate degradation machinery that only removes the disease-causing proteins and leaves normal proteins untouched."

Broad progress in strategies to clear specific damaging biochemicals from the body will benefit longevity science in the long run. Some of the resulting technologies and therapies will be repurposed in years ahead to remove metabolic byproducts that contribute to aging.

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

Why Does Calorie Restriction Improve Insulin Sensitivity? (April 03 2009)
https://www.fightaging.org/archives/2009/04/why-does-calorie-restriction-improve-insulin-sensitivity/
We know that calorie restriction (CR) greatly improves insulin sensitivity - which seems to be one of the ways in which it increases life span - just as eating too much and getting fat tends to lead to insulin resistance and the diabetes that follows. Here, researchers are making slow inroads into understanding why CR does this: "Caloric restriction (CR) has been shown to retard aging processes, extend maximal life span, and consistently increase insulin action in experimental animals. The mechanism by which CR enhances insulin action, specifically in higher species, is not precisely known. We sought to examine insulin receptor signaling and transcriptional alterations in skeletal muscle of nonhuman primates subjected to caloric restriction over a 4 year period. ... CR increases insulin sensitivity on a whole body level and enhances insulin receptor signaling in this higher species. CR in cynomolgus monkeys may alter insulin signaling in vivo by modulating protein content of insulin receptor signaling proteins."

More Regeneration Than Thought (April 03 2009)
https://www.fightaging.org/archives/2009/04/more-regeneration-than-thought/
It's been a recurring theme in recent years that cell populations once thought to be static throughout much of life do in fact generate new cells at a slow rate or after injury. That such a process exists opens the door to efforts to speed it up as an alternative to other forms of regenerative medicine. For example, scientists have "shown the human body regenerates heart cells at a rate of about one percent a year, a discovery that could one day reduce the need for transplants. The study of 50 volunteers, using a dating method that detects traces of a carbon isotope left by Cold War nuclear bomb tests, raises the prospect of artificially stimulating the renewal process some day. ... Heart cells are unusual in that they stop dividing early in life. Doctors knew there were master cells called stem cells in the heart, but heart muscle usually simply forms scar tissue after damage and never fully regenerates. ... the rate at which the new cells are produced slows as we get older, with a young adult in their twenties renewing cells at a rate of about 1 percent a year, falling to half a percent a year by the age of 75. If you exchange cells at this rate it means that even if you live a very long life you will not have exchanged more than 50 percent of your cells. So at any given time your heart is a mosaic of cells you carry with you from birth and cells that that have been added later to replace cells that have been lost during life."

Imminst TV (April 02 2009)
https://www.fightaging.org/archives/2009/04/imminst-tv/
The TV section of the Immortality Institute site is central repository and chatroom for much of the video resulting from the work of volunteers there, running on ustream. "Our Executive Director, Mind, has compiled a list of the videos that he plays in there that are posted there. He has also compiled a list of some of the main guests and links to the interviews that he conducts for imminst.org/tv's main feature, the Sunday Evening Update show ... Sunday Evening Update is held most Sunday afternoons and provides news, views, and people from the world of life extension. Hosted by Immortality Institute Executive Director Mind (Justin Loew), past special guest speaker have included [Aubrey de Grey
and S. Jay Olshansky]. ... Our channel makes use of video and audio technology, as well as a traditional text chat interface. Come by to listen to and participate in the discussion, and type your questions for the guest speakers. During the rest of the week, stop by to watch rotating documentaries or our archived chats, and participate in various meetings held by active Immortality Institute members." It's a pretty active community of pro-longevity folk, so you should make a point of passing by to see if you fit in.

How Beta-Amyloid Kills Cells in Alzheimer's (April 02 2009)
https://www.fightaging.org/archives/2009/04/how-beta-amyloid-kills-cells-in-alzheimers/
A mechanism by which beta-amyloid buildup kills brain cells is proposed over at EurekAlert!: "attacks on the mitochondrial protein Drp1 by the free radical nitric oxide - which causes a chemical reaction called S-nitrosylation - mediates neurodegeneration associated with Alzheimer's disease. Prior to this study, the mechanism by which beta-amyloid protein caused synaptic damage to neurons in Alzheimer's disease was unknown. These findings suggest that preventing S-nitrosylation of Drp1 may reduce or even prevent neurodegeneration in Alzheimer's patients. ... found that beta-amyloid can generate nitric oxide that reacts with Drp1. By identifying Drp1 as the protein responsible for synaptic injury, we now have a new target for developing drugs that may slow or stop the progression of Alzheimer's." Mitochondria are the power plants of cells; all sorts of things start to go wrong when they are systematically damaged. While its true that we've seen mice packed to the gills with beta-amyloid and suffering no harm due to it, indicating that there might be something to blocking the way in which beta-amyloid damages cells, I'd prefer to see clearance or identification and removal of the root cause of the build-up of aggregates rather than a strategy of dealing with them after the fact.

Speculating on Mitochondria and Accelerated Aging (April 01 2009)
https://www.fightaging.org/archives/2009/04/speculating-on-mitochondria-and-accelerated-aging/
Over at Ouroboros, some scientific speculation on the relationships between mitochondrial DNA (mtDNA) damage and aging that might - or might not - be illustrated by accelerated aging (or progeroid) conditions. Progeroid conditions are associated with failures of the repair processes for nuclear DNA, but how does the separate DNA in mitochondria figure in to this? "Repair mechanisms also exist for mitochondrial DNA, [but] do deficiencies in mtDNA repair play a similar role in aging? We've already seen that mitochondrial DNA damage accumulates with age. And calorie restriction, the gold standard of lifespan extension, prevents this increase in damage. ... The authors argue that the increased level of chromosomal breakage and the replicative pausing in the mutant mouse are responsible for the progeroid symptoms ... In their view, mitochondrial DNA replication is actually upregulated [so as to provide more energy] to compensate for the reduction in replication capacity. ... The phenotype of DNA repair mutants could be caused not by mutations themselves, but by the effort it takes to prevent DNA mutation from occurring past some threshold which would cause cellular catastrophe. ... Is it possible that the problem in progeroid models is not due to the DNA damage itself, but to [the energy-generation demands placed upon mitochondria in order] to prevent a catastrophic collapse of DNA integrity?"

Magnetic Cell Assembly (April 01 2009)
https://www.fightaging.org/archives/2009/04/magnetic-cell-assembly/
Researchers are presently working on a very diverse array of methodologies for tissue engineering, seeking the technology base of tomorrow that will enable cost-effective growth of replacement tissues and organs. Here is another in its early stages: "The power of magnetism may address a major problem facing bioengineers as they try to create new tissue - getting human cells to not only form structures, but to stimulate the growth of blood vessels to nourish that growth. ... magnetic particles suspended within a specialized solution act like molecular sheep dogs. In response to external magnetic fields, the shepherds nudge free-floating human cells to form chains which could potentially be integrated into approaches for creating human tissues and organs. ... The next step is to see if the spatial arrangement of these cells in three dimensions will promote vascular formation. A major hurdle in tissue engineering has been vascularization, and we hope that this technology may help to address the problem."

Taming Microglia (March 31 2009)
https://www.fightaging.org/archives/2009/03/taming-microglia/
You might recall that microglia immune cells in the brain and nervous system are implicated in the damage of aging. Evolutionary adaptations beneficial in youth come back to bite you in later life, in this case via excessive release of inflammatory cytokines. Researchers are working on ways to deal with that, however: CHPG, an activator of a type of glutamate receptor, "shuts down activation of key immune cells in the brain known as microglia, which sense pathogens or damage in the spinal cord and brain. They helpfully foster the destruction of microbial invaders and clean up biological detritus that occurs after an injury, but researchers say they have a dark side as well ... Under certain conditions, like spinal cord injury and brain trauma, microglia [release] toxic chemicals that can kill healthy adjacent tissue, and this process can continue for months. ... The team had previously found that microglial cells express a certain receptor, the group I metabotropic glutamate receptor 5 (mGluR5), on their surface. Further work showed that if these receptors were specifically activated on microglia, these immune cells would not produce the neurotoxins that led to cell death near the site of injury. CHPG serves to selectively activate the receptor, reducing microglial toxicity."

Bacterial Roots of Arthritis (March 31 2009)
https://www.fightaging.org/archives/2009/03/bacterial-roots-of-arthritis/
What triggers some immune systems to run amok, causing conditions like some types of arthritis? Here, researchers have a lead on one possible root cause: "a specific gene called NOD2 triggers arthritis or makes it worse when leftover remnants of bacteria cell walls, called muramyl dipeptide or MDP, are present. ... Despite recent advances in the treatment of arthritis, none target its cause. Our work with MDP and NOD2 is a step toward understanding the root cause of arthritis which one day may allow certain forms of arthritis to be prevented altogether. ...[Researchers] made this discovery through experiments using two groups of mice, one group was normal and the other had been genetically modified so that their NOD2 gene was deactivated (commonly referred to as 'knocked out'). Then they administered MDP to the joints of mice in each group, and unlike the normal group of mice, the mice with the deactivated NOD2 gene did not experience signs of arthritis. ... Now that we know that bacterial products can activate this NOD2 pathway and that this signal contributes to arthritis, the next step is to find treatments that either rid the body of this inflammatory signal or mask it. Either way, the net effect would be the same: people would be spared from a very crippling disease."

Looking at Stem Cell Research (March 30 2009)
https://www.fightaging.org/archives/2009/03/looking-at-stem-cell-research/
A broad, popular science look at stem cell research from the John Hopkins Magazine: "Stem cells have been regarded as the best - perhaps the last - hope for patients with certain diseases such as diabetes; if stem cells could be used inside the body to grow the pancreatic islet cells that produce insulin - cells that are ravaged by an immune response in diabetics - then, one day, injecting them into patients might reverse the disorder. The same might be true for Parkinson's disease, which afflicts 2 percent of people over age 65, and thousands of younger people. If stem cell therapies could be developed that would repair or replace damaged or dead dopamine neurons in the brain, sufferers would no longer lose control of their movements. Stem cell research affords scientists the chance to see if they can develop personalized 'drugs' that would work throughout the body, or to uncover the secrets behind the development of human tissues and the origins of disease. No other therapy or group of therapies comes close to its potential impact."

Acetylation, NuA4, and Yeast Lifespan (March 30 2009)
https://www.fightaging.org/archives/2009/03/acetylation-nua4-and-yeast-lifespan/
It's a little early to tell whether this will actually shed any light upon the metabolic processes of human longevity, even though Sir2 is involved, but it is interesting nonetheless: "making glucose is highly influenced by a large enzyme complex already known to fix damaged DNA, and which apparently affects yeast life span through a common chemical process - acetylation. ... when continuously acetylated, the so-called NuA4 enzyme complex causes yeast cells to live longer than they would under normal conditions. ... the constantly acetylated form of yeast cell can outlive the unaltered cell by 20 percent and that the constantly de-acetylated form had an 80 percent reduction in its lifespan compared to the unaltered cell. ... Because the NuA4 complex is highly conserved among species, what we've found in yeast translates to humans as well. What we've revealed about longevity in yeast perhaps someday can translate to human health. ... the team provided the first evidence that acetylation controls the activity of an enzyme called Pck1p, critical to sugar production in yeast and probably human cells. This enzyme is also controlled by the enzyme Sir2, which removes the acetyl group. Sir2 is heavily implicated in aging and a number of diseases by recent studies in mammals."

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