Microbiota protect against frailty and loss of skeletal muscle, and maintain inflammatory tone during aging in mice.

IF 5 2区 生物学 Q2 CELL BIOLOGY
Meghan O Conn, Erica N DeJong, Daniel M Marko, Russta Fayyazi, Dana Kukje Zada, Kevin P Foley, Nicole G Barra, Dawn M E Bowdish, Jonathan D Schertzer
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引用次数: 0

Abstract

Chronic low-level inflammation or "inflammaging" is hypothesized to contribute to sarcopenia and frailty. Resident microbiota are thought to promote inflammaging, frailty, and loss of skeletal muscle mass. We tested immunity and frailty in male C57BL6/N germ-free (GF), specific pathogen-free (SPF) mice, and mice that were born germ-free and colonized (COL) with an SPF microbiota. Male and female GF mice had lower systemic cellular inflammation indicated by lower blood Ly6Chigh monocytes across their lifespan. Male GF mice had lower body mass, but relative to body mass, GF mice had smaller hindlimb muscles and smaller muscle fibers compared with SPF mice across the lifespan. Male and female GF mice had increased frailty at 18 mo or older. Colonization of female GF mice increased blood Ly6Chigh monocytes but did not affect frailty at 18 mo or older. Colonization of male GF mice increased blood Ly6Chigh monocytes, skeletal muscle size, myofiber fiber size, and decreased frailty at 18 mo or older. Transcriptomic analysis of the tibialis anterior muscle revealed a microbiota-muscle axis with over 550 differentially expressed genes in COL male mice at 18 mo or older. Colonized male mice had transcripts indicative of lower tumor necrosis factor (TNF)-α signaling via nuclear factor κB (NF-κB). Our findings show that microbiota can increase systemic cellular immunity while decreasing muscle inflammation, thereby protecting against muscle loss and frailty. We also found sex differences in the role of microbiota regulating frailty. We propose that microbiota components protect against lower muscle mass and frailty across the lifespan in mice.NEW & NOTEWORTHY Germ-free mice had increased frailty, lower muscle mass, and lower circulating inflammatory monocytes. Therefore, lower systemic inflammation coincided with worse frailty and muscle loss. Microbial colonization decreased frailty, restored muscle mass, and increased circulating inflammatory monocytes while lowering transcripts in inflammatory TNF and NF-κB pathways within muscle. Hence, microbiota can increase circulating inflammation but decrease muscle inflammation to protect against frailty. This microbiota-muscle axis should be investigated for therapeutic potential in muscle wasting and sarcopenia.

在小鼠衰老过程中,微生物群可以防止虚弱、骨骼肌的丧失,并维持炎症性张力。
慢性低水平炎症或“炎症”被认为会导致肌肉减少症和虚弱。常驻微生物群被认为会促进炎症、虚弱和骨骼肌质量的损失。我们测试了雄性C57BL6/N无菌(GF)、无特异性病原体(SPF)和出生时无菌并定植SPF微生物群(COL)的小鼠的免疫力和脆弱性。雄性和雌性GF小鼠的全身细胞炎症较低,这表明在其一生中血液ly6high单核细胞较低。雄性GF小鼠的体重较低,但相对于体重,GF小鼠的后肢肌肉和肌肉纤维在整个生命周期中都比SPF小鼠小。雄性和雌性GF小鼠在18个月或更大的时候变得更加虚弱。雌性GF小鼠的定植增加了血液中的ly6high单核细胞,但对18个月或更大的虚弱没有影响。雄性GF小鼠的定植增加了血ly6high单核细胞、骨骼肌大小、肌纤维大小,并减少了18个月或更大的虚弱。对18个月或更大的COL雄性小鼠的胫骨前肌进行转录组学分析,发现有超过550个差异表达基因的微生物群-肌肉轴。定植的雄性小鼠通过核因子κB (NF-κB)表达较低的肿瘤坏死因子- α (TNF)信号。我们的研究结果表明,微生物群可以增加全身细胞免疫,同时减少肌肉炎症,从而防止肌肉损失和虚弱。我们还发现,微生物群在调节身体虚弱方面的作用存在性别差异。我们提出微生物群成分在小鼠的整个生命周期中防止肌肉质量降低和虚弱。
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
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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