Young Stem Cell Potential in Aged Mice

描述(由申请人提供)： 摘要躯体干细胞活性是补充丢失的组织特异性细胞所必需的。从成年期到老年，造血、肌肉和肠道干细胞活性下降。因此，干细胞老化可能会降低组织的动态平衡，限制寿命。因此，识别逆转或减缓干细胞衰老的机制可能会为临床干预年龄相关疾病提供新的策略。目前的范式认为，造血干细胞(HSC)的老化不能通过短期干预来逆转。挑战这一范式，我们发现，接受G-CSF诱导动员的老年动物的HSCs在组织稳态和淋巴分化方面表现为年轻。我们假设衰老的干细胞表型不是固定的，干细胞功能通过动员而恢复活力。为此，我们将调查老年动物体内动员的HSCs在功能上与年轻干细胞相似的程度，并将直接测试老年HSCs在动员后是否恢复活力。详细了解在老年动物中动员G-CSF时导致表型年轻的HSCs在外周血中积累的机制是可能翻译应用我们的发现的重要的第一步。 项目简介干细胞老化可能会降低组织的动态平衡，从而限制寿命。因此，确定逆转或减缓干细胞衰老的机制具有巨大的治疗意义。我们发现，接受G-CSF诱导动员的老年动物的HSCs表现为年轻的，并建议确定导致老年动物干细胞功能年轻的机制。

DESCRIPTION (provided by applicant): ABSTRACT 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.