Lysosomes may hold the secret to eternal youth say LSU biologists

Lysosomes, which were first identified in the late 1940s, are membrane-bound organelles in animal cells that contain digestive enzymes. They break down obsolete cell components and destroy bacteria and viruses. So, one could say lysosomes are cellular recycling stations or biological garbage dumps. Traditionally, lysosomes were thought to be spherical structures that look something like SpaghettiOs. Now, a pair of biologists at Louisiana State University (LSU), Adam Bohnert and Alyssa Johnson, have discovered complex networks of lysosomes called tubular lysosomes that can affect aging and disease. Johnson’s work mainly focuses on fruit flies, while Bohnert works with worms. A comparison to mammalian cells has revealed similar findings between different organisms. Some tissues contain tubular lysosomes, some don’t, and some can be stimulated to produce them. Under conditions of starvation, worms grow tubular lysosomes in certain organs to help them survive in the short-term, but also to have better health and longer life expectancy after the period of starvation is over. Interestingly, not only the worm but also its progeny benefit when the tubular lysosomes are passed down to future generations. For now, the discovery could help explain the effectiveness of intermittent fasting. In the future, scientists may be able to activate tubular lysosomes in human tissues to improve health, extend lifespan, and pass on the benefits to the individual’s children and grandchildren. “This is a major black box in biology where we don’t have a lot of knowledge yet,” says Bohnert. “From a very basic level, we’re now redefining the landscape of what it means to be a cell. Tubular lysosomes could hint at ways to slow down the aging process, or even reverse it. This sounds like science fiction, but it could be possible.” Johnson first identified tubular lysosomes in fruit flies and the pair have identified a couple of genes that appear to control their formation. “My first thought was – this is beautiful!’” recalls Johnson. “I had never before seen lysosomes that look like this in any cell type. At that moment, I knew in my heart that I had to study them further.” “Alyssa and I complement each other because we have expertise in different model organisms; she in flies and me in worms,” Bohnert continued. “We’ve now developed a toolkit to go in and assess on a broad level any tubular lysosome. How does it act? How does it function? How is it built? How is it stimulated?” “One of the genes, if you over-express it, can make networks in places where there normally are no networks, and this seems to correlate with animal health,” explains Johnson. “Our question is, can we introduce it in animals and tissues that don’t normally have them, to promote their health? We’re trying to understand the differences between tissues and if we can learn from one tissue to provide beneficial output for a different tissue or the whole organism in general.” When it comes to candidates for tubular lysosome studies, worms (C. elegans) are near-ideal. Their transparent bodies allow researchers to observe the network of tubular lysosomes growing and connecting or shrinking and disconnecting under a fluorescence microscope. Interestingly, the worms stay alive during the imaging process. This is essential because tubular lysosomes can only be seen in living tissue. “We’re really the only ones studying tubular lysosomes in the world, which puts us in a unique position to break open this field,” Johnson said. “There’s the basic, fundamental science part of our work and then the biomedically relevant part, where we use our new knowledge of lysosome biology to see how it could be used for therapeutic purposes. That’s what made it possible for us to get support from the Keck Foundation. We’ll do genome-wide screens, biochemical screens and broad analysis of tissues. We’ll find new genetic players that regulate and control these tubular lysosomes.” Bohnert and Johnson are not just colleagues, they’re married and have two children. Their son recently received a coloring book of cells in which the lysosomes resembled SpaghettiOs, similar to college textbooks, they recall. Their research, however, could lead to a revision in how we perceive and depict the basic biological unit of life – the cell. “The differences we’ve seen in different tissues will be really important for future studies,” Johnson concludes. “Often, people study organelles or some function of organelles in one system or cell type and make assumptions about that organelle universally. But based on what we’ve seen, that’s really not true for the lysosome. In every tissue, lysosomes look and behave quite differently.”