Every cell in your body is a busy factory, constantly engaged in turning raw materials into complex proteins via the processes of gene expression, following the blueprints in your DNA. The source of much of the necessary supply of raw materials is the cell itself: a great deal of recycling takes place as damaged proteins and larger structures such as organelles are broken down into constituent molecules that are promptly fed back into the factory process.
This recycling isn't just a matter of obtaining parts: it is quality control for cellular machinery vital to life. Autophagy is the name given to the collection of processes by which unwanted and damaged cellular components are identified and then fed into the furnaces known as lysosomes. A lysosome is a specialized organelle packed with enzymes capable of dismantling near everything it is likely to receive in the course of its duties. It engulfs the refuse and destroys it, producing useful raw materials in the process.
With time, however, our lysosomes do in fact ingest a range of items that they cannot deal with. In our long-lived cells, many of which must last a lifetime, lysosomes become bloated and malfunctioning, packed to the gills with harmful materials collectively known as lipofusin. The ability of cells to keep themselves damage-free and functional deteriorates as a consequence, and this is one of the contributing causes of degenerative aging as a whole. It is particularly important in conditions such as macular degeneration, but a long laundry list of other age-related conditions - many of them ultimately fatal - have lysosomal dysfunction and lipofuscin accumulation noted as contributed causes.
We know that this happens, and we know that it causes great harm, but what can be done to prevent it and reverse it? To answer that question, here is the latest in a series of posts on rejuvenation research by philanthropist Jason Hope.
Cells create waste products and, left unaddressed, these byproducts disable body cells to cause serious illnesses. Scientists at SENS Research Foundation Research Center are currently developing ways to remove these waste products, known as lysosomal aggregates, from cells, in order to restore the cells to health and thereby treat these illnesses or prevent their onset. To understand the nature of the scientists' work, it helpful to create a working analogy that makes understanding lysosomal aggregates easier.
Lysosomal aggregates are like non-biodegradable plastic bags and other garbage rising over the tops of landfills to pollute nearby land. Left unaddressed, unhealthy substances from the garbage disrupt the lives of plants and animals surrounding the landfill to the point of causing disease and death to those organisms. The nature of the illness and disease depends largely on the type of waste polluting the landscape. Plastic bags might entangle a bird, for example, or antifreeze may poison a passing coyote. Each toxin causes a specific effect on a particular organism.
Each particular lysosomal aggregate tends to form in a specific type of body cell. When the amount of aggregate is large enough to interfere with normal cell function, the cell can no longer carry out its function, and as more and more cells of a given type become dysfunctional it leads to illness. Age-related macular degeneration, or AMD, is an excellent example of this action. Special cells in the retina of the eye, known as retinal pigment epithelium or RPE cells, produce the waste material A2E. Many scientists think the accumulation of A2E disables RPE cells to cause the vision loss associated with AMD.
The Lysosomal Aggregates team at SENS Research Foundation Research Center is working to identify optimal A2E-degrading enzymes, and to deliver them directly into the lysosomes in the eye. In their previous work, the team had been able to identify many enzymes capable of stopping A2E in a petri dish but was unable to deliver these enzymes into an actual lysosome in an eye. They are working to develop methods to deliver these enzymes to the lysosomes. One procedure in particular, known as SENS20, works both in vitro and in actual RPE cells, but others may work even better.
Lysosomal aggregates [are also] associated with atherosclerosis, commonly known as hardening of the arteries. Oxidation can cause breakdown of the "bad cholesterol" LDL in the bloodstream. This breakdown increases the levels of 7-ketocholesterol, or 7KC, known to cause the narrowed arteries and poor cardiac function associated with atherosclerosis. Researchers from Rice University are working to develop enzymes that reduce 7KC in hopes of reversing the processes that cause atherosclerosis.
SENS Research Foundation is making great strides in reducing the devastating health effects caused by lysosomal aggregates. With continued research, the scientists hope to someday treat or prevent widespread debilitating illnesses like age-related macular degeneration and atherosclerosis.