Amyloid: Junk That Builds Up Between the Cells
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As we get older, many different types of errant and unwanted proteins, the chemical byproducts of metabolism, build up and accumulate between our cells. Collectively these are known as forms of amyloid, a term that might be familiar to you in connection with Alzheimer's disease, but there are many other types of amyloid beyond that implicated in the destruction that Alzheimer's brings to the brain. For example, the work of the Supercentenarian Research Foundation implicates a different form of amyloid in the deaths of the oldest old. Those people who - though good genes, good lifestyle choices, and good luck - manage to evade heart disease, cancer, and all the other common forms of age-related death are done in by amyloid in the end.

In TTR Amyloidosis, the protein amasses in and clogs blood vessels, forcing the heart to work harder and eventually fail. "The same thing that happens in the pipes of an old house happens in your blood vessels," says Coles.

As one of the obvious and known forms of biochemical and structural change that occurs with aging, the buildup of amyloids is a target for the Strategies for Engineered Negligible Senescence (SENS):

Extracellular junk is aggregates of stuff that do not have any function and should ideally have been cleared out of the body, but have proven resistant to destruction. Extracellular junk is different from extracellular cross-linking - it refers only to substances that do not have any function, not even a biophysical one. Most of this junk is termed "amyloid" of one variety or another. You may have heard of one form of amyloid - Abeta, the stifling, web-like material that forms plaques in the brains of patients with Alzheimer's disease, and also (more slowly) in everyone else's.

...

A strategy for reversing the accumulation of such material is being pursued by several scientific teams, including researchers with Elan Pharmaceuticals: vaccination to stimulate the cells of the immune system to clear out the material. ... the cells may eventually encounter problems in fully digesting this material - but, if so, its degradation can still be engineered by [a bioremediation approach using enzymes discovered in bacteria].

As you might know, it is in fact not so clear-cut exactly how varying forms of amyloid cause their contributions to the damage and disease of aging. Under the SENS mindset, we should still proceed as rapidly as possible to establish ways to reduce amyloid buildup to youthful levels. It doesn't matter that we don't know all the details: the sum total of what we would like to achieve is to restore an aged biochemistry to the same state it was in when it was young. We know that increased amyloid is a change that occurs with aging, and we can see how to reverse it, so the most effective course of action is to build the necessary therapies as soon as we can, even if that means doing so in advance of a complete understanding of how amyloid damages us.

On the topic of the mechanisms by which amyloid is destructive to your cells, your metabolism, and ultimately your health and life, I noticed a recent paper I should point out, though you might prefer the popular science release format instead:

It was believed that amyloid fibrils - rope-like structures made up of proteins sometimes known as fibres - are inert, but that there may be toxic phases during their formation which can damage cells and cause disease. [But] scientists at the University of Leeds have shown that amyloid fibres are in fact toxic - and that the shorter the fibre, the more toxic it becomes.

"This is a major step forward in our understanding of amyloid fibrils which play a role in such a large number of diseases," said Professor Sheena Radford of the Astbury Centre for Structural Molecular Biology and the Faculty of Biological Sciences. "We've revisited an old suspect with very surprising results. Whilst we've only looked in detail at three of the 30 or so proteins that form amyloid in human disease, our results show that the fibres they produce are indeed toxic to cells especially when they are fragmented into shorter fibres."

Amyloid deposits can accumulate at many different sites in the body or can remain localised to one particular organ or tissue, causing a range of different diseases. Amyloid deposits can be seen in the brain, in diseases such as Parkinson's and Alzheimer's, whereas in other amyloid diseases deposits can be found elsewhere in the body, in the joints, liver and many other organs. Amyloid deposits are also closely linked to the development of Type II diabetes.

Which is not terribly surprising, but it is still good support for the SENS approach of forging ahead. The only path to rapid success in engineering ways to reverse the damage of aging is to start early.


ResearchBlogging.orgXue, W., Hellewell, A., Gosal, W., Homans, S., Hewitt, E., & Radford, S. (2009). Fibril Fragmentation Enhances Amyloid Cytotoxicity Journal of Biological Chemistry, 284 (49), 34272-34282 DOI: 10.1074/jbc.M109.049809

Comments

Why not just find the fountain of youth and be done with it

Posted by: buckfutz at February 22, 2012 11:56 AM

Turmeric dissolves Amyloid in the joints and the brain.

Posted by: Andy at March 11, 2012 7:10 AM

Please tell us more about systemic enzymes with the ability to dissolve amyloid.

Posted by: JP Abello at April 7, 2012 7:32 AM

There was no mention in this article about the work being done, to discover and utilize the supposed enzymes that destroy amyloids. I have read that cemeteries are devoid of these amyloid materials due to enzymes and bacteria that must be breaking them down. Furthermore no mention was made of so called chaperone chemicals that may help to carry the unwanted materials out of the body by chelation or other such mechanisms.

Posted by: Wm. James at August 12, 2012 3:16 AM

It is a pity to see that you are not even paying attention to this very important thing called NUTRITION, with respect to aging. I mean, do you think centenarians don't get enough nutrients and somehow avoid these effects when compared with the average Joe? Come on, wake up, I get that you're holding on for biotechnology in some transhumanist hope that you can switch the aging button off, but that just isn't how the body works. The body works with nature.

Posted by: Liam Jones at January 20, 2013 8:22 AM

a paper show that amyloid in the brain is beneficial.

Posted by: Hu Ling at April 15, 2013 8:04 AM
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