This work is the Lysosens project.
Their collaboration addresses age-related problems, such as heart disease, macular degeneration, and Alzheimer’s disease, by understanding the root causes of disease. A number of diseases that appear with age are primarily caused by a lifetime of accumulated debris inside of cells.
One theory of aging is that, as the molecular junk collects in our bodies through the years, it causes the onset of disease. For example, the buildup of a vitamin A byproduct is directly responsible for the leading cause of blindness in the elderly, macular degeneration, while the accumulation of sticky proteins in the brain has been linked to Alzheimer’s disease. Every day, millions of metabolic products whiz throughout our bodies to help nourish and sustain human health. Most of the time, those that aren’t used are filtered and passed out of the body, but over time some become resistant to degradation, piling up as junk in our cells.
Our bodies are not naturally equipped to degrade these harmful substances; however, Schloendorn noticed that there is not an overabundance of these molecules in the environment. Therefore, there must be a source of natural enzymes that are capable of breaking down the cellular debris. In much the same way as the buildup of junk can put a stranglehold on the natural environment around it, the collection of these miscellaneous materials can place extreme stress on a cell. The enzymes capable of decomposing the junk are like implementing a recycling program in a landfill. They salvage the used materials and there is a possibility that the basic pieces can be reused elsewhere in the cell.
The $300,000 partnership between the Biodesign Institute and the Methuselah Foundation has proven fruitful. For example, results published in the journal Biodegradation by Rittmann’s team announced the discovery of five microbes from soil and sludge samples capable of decomposing a molecule called 7-ketocholesterol. This cholesterol variant is widely accepted as a cellular toxin and thought to be a primary culprit in the development of atherosclerosis. The body does not routinely degrade it and its accumulation causes hardening of the arteries, which in turn leads to arterial blockages and heart attacks.
The researchers are now exploring the use of microbial machinery to biodegrade 7-ketocholesterol to attempt to reverse the cause of arterial distress. The targeted decomposition of 7-ketocholesterol in humans may also open doors for the therapeutic treatment of other age-related disease. Reversal of the damage done to cells by destroying the harmful biomolecules will rejuvenate cells and make them physiologically younger. On a broad scale, this technique may eliminate death by ‘old age,’ allowing people to be younger at the cellular level, and extending not only human life, but also healthy human life.
LysoSENS Progress & Next Steps
Our teams have now cultured bacteria capable of degrading 7-ketocholestrol (implicated as a major cause of atherosclerosis and also involved in Alzheimer's disease), A2E (responsible for age-related macular degeneration) and CML, a sugar-derived protein modification which accumulates throughout the body and is associated with many of the symptoms of diabetes (this last target, although technically part of the GlycoSENS strand, is presently being handled at our Arizona laboratory). The enzymes involved in A2E degradation have been identified and we are working with Professor Janet Sparrow to test them for therapeutic benefit in cellular models of macular degeneration.
Our preliminary work on 7-ketocholesterol was recently published in the international journal Biodegradation, in the March 15th 2008 issue. Our microarray program, based at Rice University, has identified a series of enzymes implicated in 7-ketocholesterol degradation which we are now characterising and cloning into E. coli to allow more extensive testing. We will publish these results (and hopefully many others!) in the near future.
This is one of seven changes in the body that are being targeted by the Strategies for Engineered Negligible Senescence (SENS)
Biodesign Institute at Arizona State University
SENS research, MPrize and Methuselah foundation funding