Researchers at UCLA have identified a protein that slows muscle repair in aging but enhances cell survival in mice. Blocking the protein improved healing speed in older mice, though it reduced long-term stem cell resilience. The findings suggest aging involves survival strategies rather than mere decline.
A new study from the University of California, Los Angeles (UCLA), published in the journal Science, explores why aging muscles heal more slowly after injury. The research, conducted on mice, focused on muscle stem cells, which accumulate high levels of a protein called NDRG1 as they age. This protein, reaching 3.5 times higher levels in older cells compared to younger ones, dampens the mTOR signaling pathway, slowing cell activation and tissue repair.
To test NDRG1's role, scientists allowed mice to age naturally to the equivalent of about 75 human years and then inhibited the protein. Older muscle stem cells then activated more quickly, behaving like those from young mice and speeding up muscle healing after injury. However, this intervention led to fewer stem cells surviving over time, reducing the muscle's regeneration capacity after repeated injuries.
"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," said Dr. Thomas Rando, senior author and director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. He likened young stem cells to sprinters—fast but not durable—and aged ones to marathon runners—slower but resilient.
The team, led by postdoctoral scholars Jengmin Kang and Daniel Benjamin, proposes a "cellular survivorship bias," where over time, only stress-resistant but slower-repairing cells persist. Rando noted that such changes may prevent complete stem cell depletion, drawing parallels to survival adaptations in nature during harsh conditions.
Funded by organizations including the National Institutes of Health and the NOMIS Foundation, the study highlights potential costs in anti-aging therapies. "There's no free lunch," Rando cautioned, emphasizing trade-offs in boosting regeneration.
