According to Maria Carolina Florian, a stem cell biologist at the Catalan Institute for Advanced Studies, the findings explain why we age and the key cellular mechanisms that must remain in place to combat age-related diseases. provide insight into the Florian suggests that it may be possible to create drugs that can maintain this control of stem cells. It looks especially important, she says.
Signer’s lab research Blood stem cells collected from mouse bone marrow. Postdoctoral fellow Bernadette Chua first extracted bone marrow from young mice (6–12 weeks old) and isolated several types of cells (stem cells, blood cells, immune cells) to isolate them early in development. observed. She then used fluorescent molecules that stick to specific components of cells to probe each one and see how its trash was being processed.
Cells use proteasomes, protein complexes containing enzymes that instantly chew up misfolded proteins. However, Signer’s lab had previously found that, like neural stem cells, young mouse blood stem cells were less dependent on the proteasome. Instead of breaking down proteins immediately, they found that stem cells swept them out of the way, gathering them in heaps like little garbage dumps. disassembled. “By storing these misfolded proteins in one place, he thinks he is essentially preserving those resources when needed,” he says. Collecting the waste pile allows the cells to control the pace of recycling, thus avoiding going too fast or too slow.
But when Chua next examined the bone marrow of a 2-year-old mouse, she discovered a shocking breakdown in this waste management system. Older mice almost completely lost the ability to form aggresomes. At least 70% of stem cells in young mice do it, whereas in older mice she does only 5%. Instead, older mice now use more proteasomes. Signer likens the move to hitting an old car with a spare tire. “It was definitely a surprise,” says Signer.
This shift in waste management machinery is bad news for stem cells. Mice genetically engineered to not cache trash had four times fewer stem cells surviving in their bone marrow into old age. This suggests that these cells are aging and reaching their end of life faster than before.
Strange as it may sound, this difference between the enzymes goes against previous hypotheses and may prove important for efforts to harness stem cells as an anti-aging therapy. “Let’s say you want to manipulate stem cells for regenerative medicine,” says Dan Jaros, a systems biologist at Stanford University, who wasn’t involved in the research. “Before you read this, you might have thought that the really good thing was to increase proteasome activity.”
The idea of young, healthy stem cells collecting debris in a “storage center” to control the pace of life instead of consuming it immediately is “very cool,” he continues. “This suggests that a more detailed understanding of how protein quality control works in aging is needed.”
