UCLA researchers have found that specific molecular changes in mice may actually provide protective effects instead of causing harm.
As people age, muscles take longer to recover after injury, a challenge that many older adults experience firsthand.
A study from UCLA using mice points to an unexpected explanation. Muscle stem cells in older tissue build up higher levels of a specific protein that slows their ability to activate and repair damage, yet at the same time helps them endure the more stressful conditions found in aging tissue.
Published in the journal Science, the findings indicate that some biological changes linked to aging may serve a protective role rather than being purely harmful. “This has led us to a new way of thinking about aging,” said Dr. Thomas Rando, senior author of the new study and director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
“It’s counterintuitive, but the stem cells that make it through aging may actually be the least functional ones. They survive not because they’re the best at their job, but because they’re the best at surviving. That gives us a completely different lens for understanding why tissues decline with age.”
Protein buildup slows but protects cells
The team, led by postdoctoral scholars Jengmin Kang and Daniel Benjamin, analyzed muscle stem cells taken from both young and old mice. They found that levels of a protein called NDRG1 rose sharply with age, reaching about 3.5 times higher in older cells compared to younger ones. This protein acts as a brake inside the cell by suppressing the mTOR signaling pathway, which normally drives cell activation and growth.
To determine whether NDRG1 was behind the slower repair seen in older muscle, the researchers allowed mice to age naturally to roughly the equivalent of 75 human years, then inhibited the protein’s activity. Once NDRG1 was blocked, aged stem cells quickly regained youthful behavior, activating faster and improving muscle repair following injury.
This improvement came with a drawback. Without the protective influence of NDRG1, fewer stem cells remained over time, reducing the tissue’s capacity to recover from repeated damage.
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