Cells can Transfer Lysosomes, Spreading Damaging Age-Related Waste Materials
It is known that cells can transfer mitochondria from one to another under some circumstances, and here researchers demonstrate that they can transfer lysosomes as well. The lysosomes in a cell play the role of recycling units, breaking down damaged structures and waste proteins. Unfortunately there are some forms of waste that our biochemistry cannot manage, and these compounds accumulate over time into a harmful mix called lipofuscin. In old tissues, long-lived cells have clogged and malfunctioning lysosomes, unable to perform the task of recycling waste. This spirals downwards into a garbage catastrophe and the cells either die or become highly dysfunctional themselves. This process of resilient waste accumulation in lysosomes is one of the root causes of aging and age-related disease.
The research here focuses on just one form of damaged protein and one class of conditions caused by the accumulation of that protein, but the transfer of lysosomes noted by the researchers has broad implications for the more general process of lysosomal dsyfunction in aging. If cells are transferring lysosomes in all tissues then this will act to dilute damage for the worst affected cells at the cost of spreading the damage more widely within important cell populations - it will be an important determinant of the way in which damage and decline progresses. That said, this is of interest but not importance given a class of therapy that can break down the waste that makes up lipofuscin. With such a tool, capable of delivering suitable enzymes to the lysosome, it doesn't matter how the waste material spreads. The SENS Research Foundation has been working on this for a while now, mining the bacterial world for suitable enzymes. Some of these have been licensed to Human Rejuvenation Technologies, and others to Ichor Therapeutics for further development for specific therapies.
Synucleinopathies, a group of neurodegenerative diseases including Parkinson's disease, are characterized by the pathological deposition of aggregates of the misfolded α-synuclein protein into inclusions throughout the central and peripheral nervous system. Intercellular propagation (from one neuron to the next) of α-synuclein aggregates contributes to the progression of the neuropathology, but little was known about the mechanism by which spread occurs. In this study researchers used fluorescence microscopy to demonstrate that pathogenic α-synuclein fibrils travel between neurons in culture, inside lysosomal vesicles through tunneling nanotubes (TNTs), a new mechanism of intercellular communication.
After being transferred via TNTs, α-synuclein fibrils are able to recruit and induce aggregation of the soluble α-synuclein protein in the cytosol of cells receiving the fibrils, thus explaining the propagation of the disease. The scientists propose that cells overloaded with α-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. However, this results in the disease being spread to naive neurons. This study demonstrates that TNTs play a significant part in the intercellular transfer of α-synuclein fibrils and reveals the specific role of lysosomes in this process. This represents a major breakthrough in understanding the mechanisms underlying the progression of synucleinopathies. These compelling findings, together with previous reports from the same team, point to the general role of TNTs in the propagation of prion-like proteins in neurodegenerative diseases and identify TNTs as a new therapeutic target to combat the progression of these incurable diseases.
My layman's guess is that this is in fact good news. If knackered lysosomes full of lipofusin spread throughout the body, you'd only have to remove it using bacterial enzymes in a certain threshold percentage of cells or tissues in the body, rather than in every cell in the body, assuming that lysosomes full of lipofuscin move stochastically from areas of high concentration to low concentration of course.
This also does look like a classical evolutionary response to selection pressure for longer lifespans. Rather than evolve a means of removing damage from the body, just evolve a means of tolerating slightly more of that damage before crisis sets in. A lash up job.
It could potentially be of therapeutic use if the process can be manipulated. Say, if you were able to encourage most cells to be more prone to donating lysosomes, and have particular blood cells more prone to receiving them. You could then periodically remove these blood cells from the body, thereby eliminating the waste that way.
I've always suspected this is in fact how parabiosis does most of it's positive effects in vivo, not through some esoteric signaling pathways - which by the way, a decade later they've still failed to reproduce.
hmmm. would those unfortunate lipofuscin "donor" cells be senescent by definition? if so, would ablation of them via Oisin tech be an efficient approach? further, if they are not senescent, perhaps they could be programmatically ID'd and then programmed to apoptosis...?
this would obviate the "clean out" strategy...
@David Gobel: Hard to say. It would be interesting to find any work on relationships between senescence and cellular lipofuscin levels - it seems plausible that there would be a correlation to some degree, but no necessary reason that there would be given the very different numbers of cells that are senescent versus carry a lot of lipofusin.
@David
Well here is the thing. Once you tell the senescent cells to commit suicide they still need to be recycled - or you'll end up with a lot of junk outside of your cells so that means - surprise surprise, the indigestible junk will end up in yet another type of cells - although this time it will be phagocytes I suppose.
These things need to be tested. Unfortunately as of now, no one is testing them.
Is it beneficial to kill off your senescent and lipofuscin-contaminated cells, send their junk into your bloodstream, and then head to the nearest plasma donation center?