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

IF 8 1区医学 Q1 CELL 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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology

自引率

2.60%

发文量

212

期刊介绍： Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.