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）： 摘要体细胞干细胞的活性是补充丢失的组织特异性细胞所必需的。造血干细胞、肌肉干细胞和肠干细胞的活性从成年到老年逐渐下降。因此，干细胞老化可能会降低组织稳态并限制寿命。因此，确定恢复或减弱干细胞衰老的机制可能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）老化是不可逆的短期干预。根据这一范例，我们发现来自经历G-CSF诱导的动员的老年动物的HSC在组织稳态和淋巴样分化方面是表型年轻的。我们假设，老化的干细胞表型是不固定的，干细胞的功能是通过动员恢复活力。为此，我们将研究老年动物中动员的HSC在多大程度上类似于功能上年轻的干细胞，我们将直接测试老年HSC是否在动员后恢复活力。详细了解老年动物G-CSF动员后外周血中表型年轻HSC积累的机制是我们研究结果可能转化应用的重要第一步。 干细胞老化可能会降低组织的稳态，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，从经历G-CSF诱导动员的老年动物的HSC是表型年轻，并提出确定机制，导致在功能上年轻的干细胞在老年动物。