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.

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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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