肺移植受者的衰弱与贫血和端粒功能障碍有关，但与表观遗传年龄无关。

Frailty in lung transplant recipients is associated with anemia and telomere dysfunction but independent of epigenetic age.

作者信息

Kapse Bhavya, Mohanty Rashmi Prava, Wax Michael, Gao Ying, Tran Lily, Wolters Paul J, Pellegrini Matteo, Singer Jonathan P, Greenland John R

机构信息

Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA; Institute for Quantitative and Computational Biosciences - The Collaboratory, University of California Los Angeles, Los Angeles, California, USA.

出版信息

Am J Transplant. 2025 May 5. doi: 10.1016/j.ajt.2025.05.002.

DOI:10.1016/j.ajt.2025.05.002

PMID:40334844

Abstract

Frailty is a syndrome of vulnerability to stressors linked to worse outcomes before and after lung transplantation. However, the biological basis of this association is unknown. Biological correlates of aging include epigenetic reprograming, chronic inflammation, telomere dysfunction, and anemia. We hypothesized that these aging-associated biological processes would be associated with frailty in lung transplant recipients. In a nested case-control study, we compared 43 lung transplant recipients who were frail pretransplant and posttransplant with 43 nonfrail matched controls. We quantified peripheral blood leukocyte epigenetic aging (Horvath) and longevity (GrimAge) clocks, telomere length, cytokine profiles, and hemoglobin before transplant. Epigenetic clocks were correlated with age but not frailty. However, we observed hypermethylation of multiple gene pathways, including hedgehog signaling and angiogenesis, and associated decreased levels of plasma cytokines in frail recipients. Frailty was also associated with telomere dysfunction and anemia. Overall, telomere dysfunction and anemia of chronic disease were most linked to frailty in this cohort, whereas epigenetic aging and chronic inflammation were not. Understanding the heterogeneity of aging syndromes may help target interventions in frail lung transplant recipients.

摘要

衰弱是一种易受应激源影响的综合征，与肺移植前后更差的预后相关。然而，这种关联的生物学基础尚不清楚。衰老的生物学相关因素包括表观遗传重编程、慢性炎症、端粒功能障碍和贫血。我们假设这些与衰老相关的生物学过程与肺移植受者的衰弱有关。在一项巢式病例对照研究中，我们将43例移植前和移植后衰弱的肺移植受者与43例匹配的非衰弱对照进行了比较。我们在移植前对外周血白细胞的表观遗传衰老（霍瓦斯）和寿命（格里姆年龄）时钟、端粒长度、细胞因子谱和血红蛋白进行了量化。表观遗传时钟与年龄相关，但与衰弱无关。然而，我们观察到虚弱受者中多个基因通路的高甲基化，包括刺猬信号通路和血管生成，以及血浆细胞因子水平降低。衰弱还与端粒功能障碍和贫血有关。总体而言，在该队列中，端粒功能障碍和慢性病贫血与衰弱关系最为密切，而表观遗传衰老和慢性炎症则不然。了解衰老综合征的异质性可能有助于针对虚弱的肺移植受者进行干预。