具有最极端寿命的个体的多组学蓝图。

IF 10.6 1区 医学 Q1 CELL BIOLOGY
Eloy Santos-Pujol, Aleix Noguera-Castells, Marta Casado-Pelaez, Carlos A García-Prieto, Claudia Vasallo, Ignacio Campillo-Marcos, Carlos Quero-Dotor, Eva Crespo-García, Alberto Bueno-Costa, Fernando Setién, Gerardo Ferrer, Veronica Davalos, Elisabetta Mereu, Raquel Pluvinet, Carles Arribas, Carolina de la Torre, Francisco Villavicencio, Lauro Sumoy, Isabel Granada, Natalie S Coles, Pamela Acha, Francesc Solé, Mar Mallo, Caterina Mata, Sara Peregrina, Toni Gabaldón, Marc Llirós, Meritxell Pujolassos, Robert Carreras-Torres, Aleix Lluansí, Librado Jesús García-Gil, Xavier Aldeguer, Sara Samino, Pol Torné, Josep Ribalta, Montse Guardiola, Núria Amigó, Oscar Yanes, Paula Martínez, Raúl Sánchez-Vázquez, Maria A Blasco, Jose Oviedo, Bernardo Lemos, Julia Rius-Bonet, Marta Torrubiano, Marta Massip-Salcedo, Kamal A Khidir, Thong Huy Cao, Paulene A Quinn, Donald J L Jones, Salvador Macip, Eva Brigos-Barril, Mauricio Moldes, Fabio Barteri, Gerard Muntané, Hafid Laayouni, Arcadi Navarro, Manel Esteller
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引用次数: 0

摘要

以超级百岁老人为代表的极端人类寿命,在理解衰老方面提出了一个悖论:尽管年事已高,但他们保持着相对良好的健康。为了研究这种双重性,我们对世界上最长寿的人进行了高通量多组学研究,询问了她的基因组、转录组、代谢组、蛋白质组、微生物组和表观基因组,并将结果与更大的匹配队列进行了比较。新出现的图像突出了归因于每个过程的不同途径:破纪录的高龄表现为端粒磨损、异常B细胞群和克隆造血,而典型的年龄相关疾病的缺失与罕见的欧洲人群遗传变异、低炎症水平、恢复活力的细菌组和年轻的表观基因组有关。这些发现为人类衰老生物学提供了新的视角,提出了健康衰老的生物标志物,以及延长预期寿命的潜在策略。我们的结果外推到一般人群将需要更大的队列和纵向前瞻性研究来设计潜在的抗衰老干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The multiomics blueprint of the individual with the most extreme lifespan.

Extreme human lifespan, exemplified by supercentenarians, presents a paradox in understanding aging: despite advanced age, they maintain relatively good health. To investigate this duality, we have performed a high-throughput multiomics study of the world's oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts. The emerging picture highlights different pathways attributed to each process: the record-breaking advanced age is manifested by telomere attrition, abnormal B cell population, and clonal hematopoiesis, whereas absence of typical age-associated diseases is associated with rare European-population genetic variants, low inflammation levels, a rejuvenated bacteriome, and a younger epigenome. These findings provide a fresh look at human aging biology, suggesting biomarkers for healthy aging, and potential strategies to increase life expectancy. The extrapolation of our results to the general population will require larger cohorts and longitudinal prospective studies to design potential anti-aging interventions.

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来源期刊
Cell Reports Medicine
Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍: Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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