A groundbreaking study from UCLA researchers has uncovered a surprising mechanism in aging muscle stem cells: as they accumulate a protective protein called NDRG1, they become more resilient and better at surviving long-term, but they lose much of their ability to quickly repair damaged tissue.
The research, conducted in mice and published in the journal Science on January 29, 2026, shows that aged muscle stem cells have NDRG1 levels approximately 3.5 times higher than those in young cells. This protein acts as a brake on the mTOR signaling pathway, which normally drives cell activation, growth, and rapid repair. As a result, older stem cells respond more slowly to injury, leading to delayed muscle regeneration.
However, this slowdown appears to be a protective adaptation. Through a process termed “cellular survivorship bias,” stem cells that fail to accumulate sufficient NDRG1 expression die off over time in the stressful aging environment. What remains is a population of tougher, more durable cells that prioritize endurance over speed – much like marathon runners compared to sprinters.
“This has led us to a new way of thinking about aging,” said Dr. Thomas Rando, senior author of the study, director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and professor of neurology at the David Geffen School of Medicine 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.”
In experiments, when researchers blocked NDRG1 in aged mice, the stem cells reverted to a more youthful state: they activated more rapidly and repaired muscle injuries more quickly, producing larger muscle fibers within 7 days post-injury. Yet this came at a cost: fewer stem cells survived over the long term, impairing regeneration after repeated injuries.
“Think of it like a marathon runner versus a sprinter,” Rando explained. “The stem cells in young animals are hyper-functioning – really good at what they do, namely sprinting, but they’re not good for the long term. They can make it through the 100-yard dash, but they can’t make it even halfway through the marathon. By contrast, aged stem cells are like marathon runners – slower to respond, but better equipped for the long haul. However, what makes them so proficient over long distances is exactly what renders them poor at sprinting.”
The findings challenge the conventional view that all age-related cellular changes are purely harmful. Instead, some alterations may represent necessary trade-offs to prevent complete depletion of the stem cell pool – a scenario that could accelerate muscle loss and frailty even more severely.
“Some age-related changes that look detrimental – like slower tissue repair – may actually be necessary compromises that prevent something worse: the complete depletion of the stem cell pool,” Rando noted.
The study has significant implications for combating sarcopenia, the age-related loss of muscle mass and strength that affects millions and contributes to reduced mobility and independence in older adults. Simply trying to “rejuvenate” old stem cells by boosting their activity could improve short-term repair but risk long-term exhaustion of the regenerative reserve.
“There’s no free lunch,” Rando cautioned. “We can improve the function of aged cells for a period of time, for certain tissues, but every time we do this, there’s going to be a potential cost and a potential downside.”
Led by postdoctoral scholars Jengmin Kang and Daniel Benjamin, with Rando as senior author, the work compared muscle stem cells from young and old mice (aged to the human equivalent of about 75 years) in both lab cultures and living tissues.
Future research will focus on the molecular mechanisms underlying this balance in survival function, potentially enabling therapies that enhance both rapid repair and sustained stem cell viability.
The full study is available in Science (DOI: 10.1126/science.ads9175). For more on how national health and aging research may influence wellness trends and local healthcare in Lincoln and Nebraska, follow updates on LincolnCitizen.com.
