Young Stem Cell Potential in Aged Mice

老年小鼠年轻干细胞的潜力

• 批准号: 7384971
• 负责人: HARTMUT GEIGER
• 金额: $ 18.75万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384971
• 关键词: Address; Age; Animals; Appearance; Attenuated; Bone Marrow; CSF3 gene; Cell Aging; Cell Lineage; Cell physiology; Cells; Chimerism; Data; Disease; Hematopoietic; Hematopoietic stem cells; Homeostasis; Homing; Intervention; Intestines; Longevity; Lymphoid; Lymphoid Cell; Molecular; Mus; Muscle; Pathway interactions; Phenotype; Procedures; Rejuvenation; Stem cells; Testing; Therapeutic; Tissues; Transplantation; abstracting; age related; aged; cell age; fitness; juvenile animal; migration; peripheral blood; response

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.

描述（由申请人提供）： 摘要 体干细胞活性对于补充丢失的组织特异性细胞是必要的。从成年期到老年，造血、肌肉和肠道干细胞活性逐渐下降。因此，干细胞衰老可能会降低组织稳态并限制寿命。因此，确定逆转或减弱干细胞衰老的机制可能为临床干预与年龄相关的疾病提供新策略。当前的范式认为，造血干细胞（HSC）的衰老不能通过短期干预来逆转。挑战这一范式，我们发现，来自接受 G-CSF 诱导动员的老年动物的 HSC 在组织稳态和淋巴分化方面表现出年轻的表型。我们假设衰老的干细胞表型不是固定的，干细胞功能可以通过动员而恢复活力。为此，我们将研究老年动物中动员的 HSC 在多大程度上与功能上年轻的干细胞相似，并且我们将直接测试衰老的 HSC 是否在动员后恢复活力。详细了解老年动物 G-CSF 动员后导致表型年轻 HSC 在外周血中积累的机制，是我们的研究结果可能转化应用的重要第一步。 项目叙述干细胞衰老可能会降低组织稳态，从而限制寿命。因此，识别逆转或减弱干细胞衰老的机制具有巨大的治疗意义。我们发现，来自接受 G-CSF 诱导动员的老年动物的 HSC 在表型上是年轻的，并建议确定在老年动物中产生功能性年轻干细胞的机制。