This revelation offers insight into why we age and what critical cellular machinery we need to keep running to combat age-related diseases, according to Maria Carolina Florian, a stem cell biologist at the Catalan Institution for Research and Advanced Studies who was not involved in the study. job. . For Florian, it suggests the possibility of creating drugs that can maintain this control of stem cells. It seems particularly important, she says, “because of this possibility of being targeted, to be able to reverse aging.”
Signer’s lab studied blood stem cells extracted from mouse bone marrow. Doctoral researcher Bernadette Chua first took marrow from young mice (6 to 12 weeks old) and isolated various types of cells (stem cells, as well as blood and immune cells) to observe them during an early stage of development. Then, using fluorescent molecules that attach to specific components of the cell, she snooped on each one to see how it handled its garbage.
Cells use proteasomes, protein complexes that contain enzymes that immediately chew up your misfolded proteins. But Signer’s lab had previously found that, as neural stem cellsblood stem cells in young mice don’t rely too much on proteasomes. In this new experiment, Chua and Signer found that instead of breaking down the misfolded proteins right away, the stem cells removed them and collected them in piles, like little junkyards. Later, they disintegrated them with a different protein complex called an aggressor. “We think that by storing these misfolded proteins in one place, they’re basically holding onto those resources for when they need them,” Signer says. Collecting piles of waste can allow cells to control the rate of their recycling and, as a result, avoid living too fast or too slow.
However, the next time Chua examined the marrow of 2-year-old mice, he found a shocking flaw in this waste management system. The older mice almost completely lost their ability to form aggresomes: at least 70 percent of stem cells in young mice do, but only 5 percent in old mice. Instead, the old mice switched to using more proteasomes, a move Signer likens to slamming a spare tire on an old car. “That definitely came as a surprise,” Signer says.
This change in the waste control machinery is bad news for stem cells. Mice that were genetically engineered not to store their garbage had four times fewer surviving stem cells in their bone marrow into old age. It suggests that those cells are aging and expiring faster than before.
This distinction between enzymes, as bizarre as it sounds, could prove crucial to efforts to harnessing stem cells as anti-aging therapies because it goes against the above assumptions. “Let’s say you want to design a stem cell for regenerative medicine,” says Dan Jarosz, a systems biologist at Stanford University who was not involved in the work. “Before reading this, I might have thought that a really good thing would be to increase proteasome activity.”
The idea that young, healthy stem cells control the rhythm of their lives by collecting waste in a “storage center,” rather than consuming it immediately, “is very interesting,” he continues. “This suggests that we need a much more nuanced understanding of how protein quality control works in aging.”