LysoSENS

LysoSENS is the first and primary beneficiary of the funds raised by The Longevity Medical Research Fund.

LysoSENS is a SENS initiative tackling atherosclerosis and other diseases caused by the accumulation of normally benign material in the body. Their first and most urgent target is atherosclerosis, since, with its role in stroke and heart disease, it kills more Americans each year than all cancers combined.

The first stages of the work are being carried out at Arizona State. The strategy is based on work done by John Archer (Cambridge), Jay Jerome (Vanderbilt), Ana Marie Cuervo (Albert Einstein), Roscoe Brady (NINDS), Perry McCarty (Stanford), Pedro Alvarez (Rice), and Bruce Rittman (Arizona State).

Their strategy is to target build-up of usually-benign metabolic by-products that in sufficient quantity become precursors to age-related disease. LysoSENS currently focuses on the subset of these molecules that accumulate in lysosomes, the cell's garbage can and degredation site of last resort.

   Lysosomal Enhancement Strategy

   Target Diseases of LysoSENS

   FAQ

For more on LysoSENS's work:

   LysoSENS site

   How you can contribute more directly to this effort

   More on how you can contribute directly to this effort

   How to make a recurring pledge, more directly to SENS research, for the price of a cup of coffee a day

   A Technical Talk on Atherosclerotic Pathogenesis

   A Technical Talk on Lysosomal Enhancement/Bioremediation in General

   A Technical Paper on Lysosomal Enhancement/Bioremediation in General

Most molecules absorbed by lysosomes are decomposed by powerful enzymes and rereleased. There are, of course, macromolecules that our lysosomes can't degrade. Lysosomes try to do us a favor by just containing such molecules, instead of rereleasing them. In certain cases this eventually backfires, the lysosomes bloating enough to create a cascade of cellular malfunction and damage to surrounding tissue. The lysosomes therefore need some help, some sort of enhancement, to enable them to degrade what they normally can't.

The solution is similar to that currently used for people born without the normal range of lysosomal enzymes: periodic enzyme injections. The twist for LysoSENS is to develop enzymes that don't normally occur in humans.

In the case of atherosclerosis, the undegradable culprit building up in lysosomes is called 7-ketocholesterol. The particular lysosomes accumulating this molecule live in phagocytes in the inner lining of artery walls. Phagocytes are cells which let in a greater variety of molecules than the average cell, since their purpose is to scavenge. This is why other cells don't have the same problem with 7-ketocholesterol: they don't let it in in the first place.

Eventually, up to 80% of cell volume is lysosomal (<5% is normal). The phagocytes bloat enough to create lesions in the inner artery lining. Plaques develop, attracting white blood cells (inflammatory immune response), cholesterol, and other debris. Artery blockage and stroke result. Ironically, cholesterol is both the cause and the effect of atherosclerosis. Building up first inside arterial cells then on the arterial wall, cholesterol arises at both the start and end of the atherogenic process. The goal of lysosomal enhancement is to eliminate the first, as a more effective alternative to lowering the second.

Fortunately, bacterial fungi exist in nature that degrade 7-ketocholesterol. The aim is therefore to modify their enzymes to maximize delivery to and efficacy in human lysosomes and minimize side effects. More can be read about these issues on the LysoSENS FAQ page.