How to Deliver New Enzymes to Clean Up Aged Cells

Medical bioremediation is the name given to the SENS Foundation approach to removing one class of harmful waste chemicals that accumulate in our cells with advancing age:

Cells have a lot of reasons to break down big molecules and structures into their component parts, and a lot of ways to do so. Unfortunately, one of the main reasons to break things down is because they have been chemically modified so that they no longer work, and sometimes these chemical modifications create structures that are so weird that none of the cell's degradation machinery works on them. This situation is very rare, but in the long run these modified chemicals add up.

Ultimately the chemicals end up in the lysosome, a special vessel that contains the most powerful degradation machinery in the cell. If something can't be broken down there, it just stays there forever. This doesn't matter in cells that divide regularly, because division dilutes the junk enough that it remains at harmlessly low levels, but non-dividing cells gradually fill up with this stuff, making them dysfunctional. The heart, the back of the eye, some nerve cells (especially motor neurons) and, most of all, white blood cells trapped within the artery wall all suffer from this.

The development of therapies of biomedical remediation breaks down into two distinct lines of research: firstly, to identify naturally occurring bacterial enzymes that digest these unwanted junk chemicals. We know that bacteria containing these enzymes exist because we find no remnants of this chemical junk in graveyards, battlefields, slaughterhouse grounds, and so forth. The SENS Foundation funds a program aimed at discovering enzymes that will be safe to introduce into the human body, and have achieved some degree of success in recent years.

The second theme in biomedical remediation research is the delivery of suitable enzymes to where they are needed: the lysosomes within our cells. Fortunately, this is an area in which many researchers are already hard at work. There exists a category of genetic disorders, the lysosomal storage diseases, in which the lysosome is dysfunctional or lacks one or more vital enzymes. Advances in repairing these conditions by delivering the correct enzymes to a patient's lysosomes are also applicable to biomedical remediation aimed at rejuvenating the malfunctioning, clogged-up lysosomes of the elderly.

Here's a recent paper from the ahead of print queue at Rejuvenation Research:

New Strategies for Enzyme Replacement Therapy for Lysosomal Storage Diseases

Enzyme replacement therapy is an established means of treating lysosomal storage diseases. Infused enzymes are normally targeted to the lysosomes of affected cells by interactions with cell-surface receptors that recognize [portions of the] enzymes. Therefore, we have investigated alternative strategies ... These strategies for delivering lysosomal enzymes could also be used to target nonlysosomal proteins or enzymes identified for bioremediation of other conditions.

This is an age of barnstorming and hacking in biotechnology - there are lot of very clever and complex things that can be accomplished with the present day tools and knowledge of human biochemistry. The paper above also illustrates the wide application of many areas of life science research. Tools aimed at specific human conditions may in the future be adapted to serve as part of a technology capable of repairing some of the damage of aging.

ResearchBlogging.orgGrubb, J., Vogler, C., & Sly, W. (2010). New Strategies for Enzyme Replacement Therapy for Lysosomal Storage Diseases Rejuvenation Research DOI: 10.1089/rej.2009.0920

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