Tissue-specific functions of MSCs are linked to homeostatic muscle maintenance and alter with aging.

Tamaki Kurosawa, Madoka Ikemoto-Uezumi, Yuki Yoshimoto, Keitaro Minato, Noriyuki Kaji, Takashi Chaen, Eiji Hase, Takeo Minamikawa, Takeshi Yasui, Kazuhide Horiguchi, Satoshi Iino, Masatoshi Hori, Akiyoshi Uezumi

Laboratory of Veterinary Pharmacology, Department of Veterinary Medical Sciences, Graduate School of Agriculture and Life Sciences, Tokyo University, Bunkyo-ku, Tokyo, Japan. · pubmed

Paper

Abstract

Mesenchymal stromal cells (MSCs), also known as fibro-adipogenic progenitors, play a critical role in muscle maintenance and sarcopenia development. Although analogous MSCs are present in various tissues, recent single-cell RNA-seq studies have revealed the inter-tissue heterogeneity of MSCs. However, the functional significance of MSC heterogeneity and its role in aging remain unclear. Here, we investigated the properties of MSCs and their age-related changes in seven mouse tissues through histological, cell culture, and genetic examinations. The tissue of origin had a greater impact on the MSC transcriptome than aging. By first analyzing age-related changes, we found that Kera is exclusively expressed in muscle MSCs and significantly down-regulated by aging. Kera knockout mice recapitulated some sarcopenic phenotypes including reduced muscle mass and specific force, revealing the functional importance of Kera in the maintenance of muscle youth. These results suggest that MSCs have tissue-specific supportive functions and that deterioration in these functions may trigger tissue aging.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the role of mesenchymal stromal cells (MSCs) in muscle maintenance and their age-related changes, which are pertinent to understanding the mechanisms of aging and potential interventions for age-related muscle deterioration (sarcopenia). While it provides solid research on the functional significance of MSC heterogeneity and its implications for muscle aging, the findings appear to be incremental rather than groundbreaking, limiting its overall impact on the field of longevity research.

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