A LysoSENS Update

LysoSENS is a project of the SENS Foundation aimed at developing a means to safely remove harmful metabolic byproducts (such as 7KC) that accumulate in lysosomes with age. That buildup degrades the lysosomal ability to clear cells of unwanted junk, which in turn leads to what is known as the garbage catastrophe in aging. At the moment, LysoSENS work focuses on discovering bacterial enzymes that can break down the most important forms of unwanted junk in the lysosome. Here is a progress report from one of the researchers: "The 7KC-degrading bacterium I've been studying, Rhodococcus jostii RHA1, has two large gene clusters that are up-regulated by 7KC, but not cholesterol. In these two gene clusters lie a number of enzymes we believe are involved in 7KC degradation, including an enzyme that could reduce the 7-keto group to a hydroxyl. What makes this interesting to us is that while 7KC is highly cytotoxic, 7alpha-hydroxycholesterol (7alphaOH) is relatively harmless. So I am now methodically going through suspected candidates, searching for reductase activity against 7KC. Currently I am looking at nine different enzymes, and am in various stages of cloning the genes into expression vectors and assaying their products for activity. While I've uncovered some interesting findings, so far I haven’t found the reductase I'm looking for. This could be for several reasons, the first being that I haven't assayed all the enzymes I need to. As I still have the majority remaining, this is a likely scenario. However, one possibility is that the normal substrate for the enzyme is not 7KC, but some downstream metabolite."

Link: http://www.sens.org/node/1261

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