An Independent Group Working on a LysoSENS Medical Bioremediation Program

This is an interesting and welcome development; a group independent of the SENS Research Foundation and its scientific network has chosen of their own accord to work on one of the LysoSENS rejuvenation research programs. This sort of thing is a sign of progress, a point at which newcomers turn up out of the blue and pitch in with no prompting required. The team is in the early stages of assessing bacterial species for their ability to break down 7-ketocholesterol, a form of metabolic waste important in aging. Cells struggle to degrade this and similar forms of oxidized lipids, and a faster progression of atherosclerosis is one of the numerous consequences. The next step for the team is to identify the specific enzymes employed by promising bacterial species, and assess them for potential use as the basis for a therapy.

Intrinsic insufficiencies in cellular catabolism and transport, particularly in post-mitotic and senile cells, lead to the build up of specific compounds that exert deleterious effects on cellular function and viability. One example of accumulation of pathogenic compounds is the formation of transformed oxysterols that exhibit cytotoxicity towards mammalian cells and are shown to participate in the pathogenesis of several age-related diseases. The major intracellular cholesterol oxide, 7-ketocholesterol, has been involved in pathogenesis of age-related diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This compound is a natural oxysterol produced via autooxidation of cholesterol and cholesterol-fatty acid esters and mainly found in oxidized lipoprotein deposits associated with atheromatous plaques.

Therefore, the delivery of microbial sterol-catabolizing enzymes into affected cell types may be advantageous for controlling elevated 7-ketocholesterol levels, and consequently help to reduce the severity of the diseases associated with the accumulation of this oxysterol. Several human enzymes are capable of metabolizing 7-ketocholesterol, but the main limitation is their localization in cellular compartments other than the lysosomes that makes them not very efficient at preventing lysosomal membrane permeabilization as well as resulting death-signalling cascade. The goal of this study was to isolate the microorganisms with high catabolic activity towards 7-ketocholesterol from diverse environmental samples (sea water sediment, soil, manure piles).

Four bacterial isolates, showing high catabolic activity towards 7-ketocholesterol were isolated: Alcanivorax jadensis IP4 (sea water sediment), Streptomyces auratus IP2 (soil), Serratia marcescens IP3 (soil) and Thermobifida fusca IP1 (manure piles). All the isolates were capable of utilizing 7-ketocholesterol as the sole organic substrate, resulting in its mineralisation. Overall, these results support the notion that oxysterol levels might be controlled by biodegradation processes, and further investigation of specific microbial enzymes involved in catabolism as well as the specific pathways involved in microbial 7-ketocholesterol degradation can be the next goals leading to come up with identifying enzymes capable of transforming oxysterols for potential environmental, industrial, pharmaceutical, and medical applications.



What is interesting what is their background. And what prompted them to choose this subject?... Did they attend years ago one of the Avery's presentations ?

Posted by: Cuberat at September 19th, 2018 6:37 AM

How can I get the paper for free. I thought Sci-Hub in the past could open such locked papers, but not now.

Posted by: thomasa at September 19th, 2018 7:49 AM

Fantastic! Very exiting news! We in our University plan to use the same approach for lipofuscin (initially for one form) so maybe there will be 4th group in the near future!

Posted by: Ariel at September 19th, 2018 2:10 PM

Were you directly inspired by SENS or there was some other instigator ?

Posted by: cuberat at September 19th, 2018 4:21 PM

@thomasa: Sci-Hub works for me for the DOI on this paper.

Posted by: Reason at September 19th, 2018 4:47 PM

Seeing scientists from Pakistan and India looking into this, it made me think it could be a smart plan to build major R&D corporations. Building up conventional pharmaceutical corporations is next to impossible, as you have to compete against already established corporations. Its like starting a new auto company.

But in whole new areas that are opening up, there is no established players. And indeed its hard for large organizations to go into new areas.

Posted by: aa3 at September 19th, 2018 9:20 PM

@cuberat, by SENS and Spiegel group.

Posted by: Ariel at September 19th, 2018 10:23 PM

That would be much better if supports such research, instead of NMN or Mouse Age. This is the real rejuvenation biotechnology which aim to remove one of the primary type of damage. Also, people like @Sinclair or @Zhavoronkov are rich and their companies have enough money for their own projects . This is some shame to fund them via public service!

Posted by: Ariel at September 19th, 2018 10:31 PM

@Ariel: LEAF's people are supporters of the Hallmarks, so don't hold your breath.

Posted by: Antonio at September 20th, 2018 5:32 PM

Good grief you two really are something. I am going to explain this to you very simply.

Ariel, like a number of people you seem confused about how our fundraising model works. We do not choose which researchers approach us with projects, the researchers themselves decide if crowdfunding is a model they wish to use. That means if you want to see more of the kinds of project you personally support hosted on then you should encourage those researchers to approach us and propose a project.

That said, SENS has confirmed they will be hosting MitoSENS early next year with us and it has some really exciting potential with the scope of what is being proposed. But if you want to see SENS hosting projects with us more often than encourage them to launch more on the platform. That simple. We cannot force researchers to crowdfund.

Not even going to address the ignorant comment about hallmarks. I am interested in science not religion.

Posted by: Steve Hill at September 21st, 2018 3:32 AM

Long ago I decided not read again comments of someone who lies about what I say, so whatever he said, I don't care.

Posted by: Antonio at September 21st, 2018 12:12 PM

And yet he cared enough to tell me he didnt care and to make an ignorant dogmatic comment about science and the people at my org he knew i would read. Lol

Posted by: Steve Hill at September 21st, 2018 1:10 PM
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