LysoSENS Work on CML Targeting

As I'm sure you recall, LysoSENS is one form of longevity research funded by the Methuselah Foundation. Broadly, it is directed towards the use of bacterial enzymes to degrade harmful metabolic byproducts that build up over time. These byproducts are associated with age-related degeneration and a range of diseases related to the failure of the lysosome, the overwhelmed cellular garbage collector. Keep these byproducts below the level of causing damage, and you'll shut down one of the root causes of aging - so is the theory. Easier said than done, of course, as is any worthwhile goal, but folk are working on it now.

In every case, it is thought that the selective removal of the respective substances would be extremely beneficial, although obviously nobody has directly tested this. LysoSENS is an attempt to do just that, in the worst case paving the ground for rethinking what age-related storage diseases are all about, and in the best case providing a cure for them.

There are many different types of damaging metabolic byproduct, and thus many threads of research to find the keys to degrade them. Over at the Methuselah Foundation forums, you'll find one such line of work outlined for the layman:

CML (Carboxymethyllysine) is a chemical modification of lysine residues on proteins. It forms as a result of a sequence of reactions that begin with sugar molecules. In general such reactions can lead to the formation of Advanced Glycation Endproducts (AGEs), and CML is one of these.


A lot of AGEs cause chemical crosslinking between proteins. Your intuitive ideas of how this could be bad are probably accurate. Imagine if you started randomly soldering pieces together under the hood of a car. Now imagine that there are a million times as many types of pieces and spread out the soldering over a hundred years.


the circumstantial evidence linking CML to age-related diseases, nevermind the mechanisms, is pretty strong.

One reason we're excited about the possiblity of finding enzymes to remove CML from the body (actually, we probably want to find a way to just remove the "CM" part) is that CML might be low-hanging fruit as far as AGEs go - primarily, because it's not a crosslink. Because it's not a crosslink, it might be much more physically accessible to enzymatic remediation.

As for the cleverness of our particular schemes to find enzymes that specifically remove the "CM" from the "L", I'll leave that for someone else or for another night...

It's exciting to watch this sort of work underway - even more so if you're one of the forward-looking folk who helped to fund this research. This is your generosity at work, enabling young scientists who support healthy life extension to work towards creating more healthy years for all of us.

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