University of Pittsburgh scientists have used stem cells derived from younger young mice to revitalize older mice. They used mice that were bred to age quickly, but after these stem cell injections, they seemed to have sipped from the fountain of youth. These stem cells were derived from muscles of young, healthy animals, and instead of becoming infirm and dying early as untreated mice did, the injected animals improved their health and lived two to three times longer than expected. These findings were published in the Jan. 3 edition of Nature Communications.
Previous research has revealed stem cell dysfunction, such as poor replication and differentiation, in a variety of tissues in old age. However it is not clear whether that loss of function contributes to the aging process or is a result of it. Senior investigators in this work were Johnny Huard, Ph.D., professor in the Departments of Orthopaedic Surgery and of Microbiology and Molecular Genetics, Pitt School of Medicine, and director of the Stem Cell Research Center at Pitt and Children’s Hospital of PIttsburgh of UPMC, and Laura Niedernhofer, M.D., Ph.D. associate professor in Pitt’s Department of Microbiology and Molecular Genetics and the University of Pittsburgh Cancer Institute (UPCI).
Niedernhofer explained: “Our experiments showed that mice that have progeria, a disorder of premature aging, were healthier and lived longer after an injection of stem cells from young, healthy animals. That tells us that stem cell dysfunction is a cause of the changes we see with aging.”
The research team examined a stem/progenitor cell population derived from the muscle of mice engineered to suffer from a genetic disease called progeria. Progeria is a genetic disease that causes premature aging. Human patients with progeria age extremely quickly and die at a very young age from old age. Muscle-derived stem cells from progeria mice were fewer in number, did not replicate as often, didn’t differentiate as readily into specialized cells and were impaired in their ability to regenerate damaged muscle in comparison to those found in normal rodents. The same defects were discovered in the stem/progenitor cells isolated from very old mice.
Dr. Huard said: “We wanted to see if we could rescue these rapidly aging animals, so we injected stem/progenitor cells from young, healthy mice into the abdomens of 17-day-old progeria mice. Typically the progeria mice die at around 21 to 28 days of age, but the treated animals lived far longer – some even lived beyond 66 days. They also were in better general health.”
As the progeria mice age, they lose muscle mass in their hind limbs, hunch over, tremble, and move slowly and awkwardly. Affected mice received an injection of stem cells just before showing the first signs of aging were more like normal mice, and they grew almost as large. Closer examination showed new blood vessel growth in the brain and muscle, even though the stem/progenitor cells weren’t detected in those tissues. However, the injected cells didn’t migrate to any particular tissue after injection into the abdomen.
Niedernhofer noted: “This leads us to think that healthy cells secrete factors to create an environment that help correct the dysfunction present in the native stem cell population and aged tissue. In a culture dish experiment, we put young stem cells close to, but not touching, progeria stem cells, and the unhealthy cells functionally improved.”
Animals that age normally were not treated with stem/progenitor cells, but these provocative findings urge further research. They hint that it might be possible one day to forestall the biological declines associated with aging by delivering a shot of youthful vigor, particularly if specific rejuvenating proteins or molecules produced by the stem cells could be identified and isolated.