B cell senescence promotes age‐related changes in oral microbiota

Author:

Mizuno Hiroya1,Kawamoto Shimpei1ORCID,Uemura Ken1,Park Jeong Hoon1,Hori Nozomi1,Okumura Yumiko1,Konishi Yusuke1,Hara Eiji123ORCID

Affiliation:

1. Department of Molecular Biology, Research Institute for Microbial Diseases Osaka University Suita Osaka Japan

2. Laboratory of Aging Biology, Immunology Frontier Research Center Osaka University Suita Osaka Japan

3. Center for Infectious Disease Education and Research Osaka University Suita Osaka Japan

Abstract

AbstractIn recent years, there has been increasing attention towards understanding the relationship between age‐related alterations in the oral microbiota and age‐associated diseases, with reports emphasizing the significance of maintaining a balanced oral microbiota for host health. However, the precise mechanisms underlying age‐related changes in the oral microbiota remain elusive. We recently reported that cellular senescence of ileal germinal center (GC) B cells, triggered by the persistent presence of commensal bacteria, results in diminished IgA production with aging and subsequent alterations in the gut microbiota. Consequently, we hypothesize that a similar phenomenon may occur in the oral cavity, potentially contributing to age‐related changes in the oral microbiota. Examination of p16‐luc mice, wherein the expression of the senescent cell marker p16INK4a can be visualized, raised under specific pathogen‐free (SPF) or germ‐free (GF) conditions, indicated that, unlike ileal GC B cells, the accumulation of senescent cells in GC B cells of cervical lymph nodes increases with age regardless of the presence of commensal bacteria. Furthermore, longitudinal studies utilizing the same individual mice throughout their lifespan revealed concurrent age‐related alterations in the composition of the oral microbiota and a decline in salivary IgA secretion. Further investigation involving Rag1−/− mice transplanted with B cells from wild‐type or p16INK4a and p21Waf1/Cip1 ‐double knockout mice unveiled that B cell senescence leads to reduced IgA secretion and alteration of the oral microbiota. These findings advance our understanding of the mechanism of age‐associated changes in the oral microbiota and open up possibilities of their control.

Funder

Japan Society for the Promotion of Science

Mitsubishi Foundation

Naito Foundation

Princess Takamatsu Cancer Research Fund

Japan Science and Technology Agency

Kato Memorial Bioscience Foundation

Foundation for Biomedical Research and Innovation

Japan Agency for Medical Research and Development

Ube Foundation

Takeda Science Foundation

Publisher

Wiley

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