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Rejuvenated Stem Cells Offer Clues to Aging

Scientists at Cincinnati Children's Hospital Medical Center (US) and the Ulm University Medicine in Germany reported their findings online May 3 in Cell Stem Cell. The study counters what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention.

HSCs originate in the bone marrow and generate all of the body's red and white blood cells and platelets. As aging occurs, HSCs become more numerous but less effective at regenerating blood cells and immune cells. This makes older people more susceptible to infections and disease, including leukemia.

Researchers in the current study determined a protein that regulates cell signaling - Cdc42 - also controls a molecular process that causes HSCs from mice to age. Pharmacologic inhibition of Cdc42 reversed HSC aging and restored function similar to that of younger stem cells, explained Hartmut Geiger, PhD, the study's principal investigator.

"Aging is interesting, in part because we still don't understand how we age," Geiger said. "Our findings suggest a novel and important role for Cdc42 and identify its activity as a target for ameliorating natural HSC aging. We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body."

The findings are early and involve laboratory manipulation of mouse cells, so it remains to any direct application to humans is uncertain. Still, the study expands what is known about the basic molecular and cellular mechanisms of aging - a necessary step to designing rational approaches to aiding a healthy aging process.

Researchers next plan to test the Cdc42 inhibitor CASIN in mice to see how HSCs and various tissues in the laboratory models respond. In particular, they are testing red blood cell production, endurance and immune response in the mice. The team is also acquiring samples of human HSCs to see how those cells respond in laboratory tests to Cdc42 expression.

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