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.