Scientists have been able to reverse brain aging and memory loss in mice

Clive Svendsen, Ph.D., executive director of the Board of Governors Institute for Regenerative Medicine and senior author of the study, explained the team’s innovative approach. “Previous studies have shown that transfusions of blood or plasma from young mice improved cognitive decline in older mice, but it is difficult to translate this into a treatment,” Svendsen said. “Our approach was to use young immune cells that we could make in the laboratory – and we found that they had beneficial effects in both aged mice and mouse models of Alzheimer’s disease.”

Formation of young immune cells from stem cells

The cells, known as mononuclear phagocytes, normally circulate through the body to remove harmful substances. However, their function diminishes as organisms age. To produce young versions, the researchers used human pluripotent stem cells — adult cells reprogrammed to an early embryo-like state — to generate young mononuclear macrophages.

When these lab-grown immune cells were injected into aging mice and mouse models of Alzheimer’s disease, scientists observed marked improvements in brain function and structure.

Improving memory and brain cell health

The mice that received the young immune cells outperformed the untreated mice on memory tests. Their brains also contained more “mill cells” within the hippocampus, an area essential for learning and memory.

“Algal cell numbers decline with age and Alzheimer’s disease,” said Alexandra Moser, a project scientist in Svendsen’s lab and lead author of the study. “We did not see this reduction in mice receiving young mononuclear macrophages, and we think this may be responsible for some of the memory improvements we observed.”

In addition, the treated mice had healthier microglia, which are specialized immune cells in the brain responsible for detecting and removing damaged tissue. Normally, microglia lose their long, thin branches as the brain ages or in Alzheimer’s disease, but in the treated mice, these branches remained expanded and active, indicating preserved immune and cognitive function.

How the treatment might work

The exact mechanism behind these benefits is not yet clear. Because mononuclear macrophages do not appear to cross into the brain, researchers believe they may affect brain health indirectly.

The team proposes several possibilities: The cells could release anti-aging proteins or small extracellular vesicles that are able to enter the brain, or they might remove aging factors from the bloodstream, protecting the brain from harmful effects. Ongoing studies aim to determine the exact mechanism and determine how best to translate these findings into human treatments.

Towards personalized anti-aging treatments

Jeffrey A. said: “Because these young immune cells are created from stem cells, they can be used as personalized therapy with unlimited availability,” said Golden, MD, executive vice provost for education and research. “These results show that short-term treatment improved cognition and brain health, making it a promising candidate for treating age-related cognitive decline and Alzheimer’s disease.”

Additional authors include Luz Jovita Dimas-Harms, Rachel M. Lipman, Jake Inzalaco, Sean Bell, Michelle Alcantara, Erika Valenzuela, George Lawless, Simon Kramer, Sarah J. Parker,andHelen S. Goodridge.

Funding: This work was supported by the Universal Sunlight Foundation, the Cedars-Sinai Center for Translational Gerontology, and the Cedars-Sinai Board of Directors Institute for Regenerative Medicine.