A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring

IF 7.1 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Aging Cell Pub Date : 2024-09-25 DOI:10.1111/acel.14351
Todd W. Dowrey, Samuel F. Cranston, Nicholas Skvir, Yvonne Lok, Brian Gould, Bradley Petrowitz, Daniel Villar, Jidong Shan, Marianne James, Mark Dodge, Anna C. Belkina, Richard M. Giadone, Sofiya Milman, Paola Sebastiani, Thomas T. Perls, Stacy L. Andersen, George J. Murphy
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Abstract

Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 96 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in molecular aging clocks to compare and contrast differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells (PBMCs) from 20 of these subjects were then successfully reprogrammed into high-quality induced pluripotent stem cell (iPSC) lines which were functionally characterized for pluripotency, genomic stability, and the ability to undergo directed differentiation. The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease.

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百岁老人及其后代的诱导多能干细胞长寿库。
百岁老人为研究长寿、健康老龄化和恢复能力提供了一个独特的视角。此外,人类衰老和抗病能力模型几乎不存在,因此无法测试潜在的干预措施。我们获得了超过 96 个百岁老人及其后代的外周血样本,并对其进行了特征描述,其中包括与功能独立性数据相关的样本,这些数据突出显示了百岁老人对残疾和认知障碍的抵抗力。在分子衰老时钟中使用了靶向甲基化阵列,以比较和对比这些特殊对象的生物年龄和计时年龄之间的差异。然后,成功地将其中 20 名受试者的分离外周血单核细胞(PBMC)重编程为高质量的诱导多能干细胞(iPSC)系,并对这些细胞系的多能性、基因组稳定性和定向分化能力进行了功能表征。这项工作的成果是研究人类长寿和恢复能力的独一无二的资源,可以促进发现和验证治疗衰老相关疾病的新型疗法。
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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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