The Body Does Work to Break Down Damaging Aggregates

One of the causes of age-related degeneration and disease is the buildup of amyloid clumps and other forms of aggregated metabolic byproducts. A brief outline:

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.

Via the Gerontology Research Group mailing list, my attention was drawn to the recent discovery of a biological process that works to remove aggregates such as amyloid. Evidently our tissues are not doing this well enough, and it is plausible that the mechanism itself declines with aging due to the accumulation of other forms of biochemical damage. But where there is a mechanism, there is the opportunity to manipulate that mechanism - to either restore its operation to youthful levels, or greatly enhance its performance. This may form a useful strategy that could be developed in competion with the SENS approach of training the immune system to attack and destroy amyloid. But here is the paper:

Discovery and characterization of a mammalian amyloid disaggregation activity:

The formation of amyloid, a cross-beta-sheet fibrillar aggregate, is associated with a variety of aging-associated degenerative diseases. Herein, we report the existence of a mammalian amyloid disaggregase activity that is present in all tissues and cell types tested. Homogenates from mammalian tissues and cell lines are able to disaggregate amyloid fibrils ... Amyloid disaggregation and proteolysis activities are remarkably resistant to changes in temperature and pH. Identification and manipulation of the proteins responsible for the amyloid disaggregation/degradation activities offers the possibility of ameliorating aggregation-associated diseases.

There is clearly a lot of work to be done here to validate and expand upon this finding. Immune therapies aimed at training the immune system to destroy specific targets, on the other hand, are much more advanced - trials have taken place in recent years, and a growing and well funded research community exists.

ResearchBlogging.orgMurray AN, Solomon JP, Balch WE, & Kelly JW (2010). Discovery and characterization of a mammalian amyloid disaggregation activity. Protein science : a publication of the Protein Society PMID: 20162625


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