Somatic stem cell activity is necessary to replenish lost tissue-specific cells. Hematopoietic, muscle and intestinal stem cell activity declines from adulthood to old age. Consequently, stem cell aging may reduce tissue homeostasis and limit lifespan. Identifying mechanisms to revert or attenuate stem cell aging may therefore offer new strategies to clinically intervene in age-related disorders. The current paradigm holds that hematopoietic stem cell (HSC) aging is not reversible by short-term interventions. Challenging this paradigm, we found that HSCs from aged animals that underwent G-CSF- induced mobilization are phenotypically young with respect to tissue homeostasis and lymphoid differentiation. We hypothesize that the aged stem cell phenotype is not fixed, and that stem cell function is rejuvenated by mobilization. To this end, we will investigate the extent to which mobilized HSCs in aged animals resemble functionally young stem cells and we will directly test whether aged HSCs are rejuvenated upon mobilization. A detailed understanding of the mechanisms that result in the accumulation of phenotypically young HSCs in peripheral blood upon G-CSF mobilization in aged animals are important first steps towards possible translational applications of our findings. PROJECT NARRATIVE Stem cell aging may reduce tissue homeostasis and consequently limit lifespan. Identifying mechanisms that revert or attenuate stem cell aging has therefore enormous therapeutic implications. We found that HSCs from aged animals that underwent G-CSF-induced mobilization are phenotypically young and propose to identify the mechanism that results in functionally young stem cells in aged animals.
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