Mizuno Hiroya, Kawamoto Shimpei, Uemura Ken, Park Jeong Hoon, Hori Nozomi, Okumura Yumiko, Konishi Yusuke, Hara Eiji
Department of Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Laboratory of Aging Biology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
Aging Cell. 2024 Dec;23(12):e14304. doi: 10.1111/acel.14304. Epub 2024 Aug 9.
In 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 p16 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 p16 and p21 -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.
近年来，人们越来越关注口腔微生物群与年龄相关变化和年龄相关疾病之间的关系，有报告强调维持口腔微生物群平衡对宿主健康的重要性。然而，口腔微生物群与年龄相关变化的具体机制仍不清楚。我们最近报道，由共生细菌的持续存在引发的回肠生发中心（GC）B细胞的细胞衰老，会导致随着年龄增长IgA产生减少以及随后肠道微生物群的改变。因此，我们推测类似的现象可能发生在口腔中，这可能导致口腔微生物群与年龄相关的变化。对p16-luc小鼠（其中衰老细胞标志物p16的表达可以可视化）在特定无病原体（SPF）或无菌（GF）条件下饲养的检查表明，与回肠GC B细胞不同，无论共生细菌是否存在，颈淋巴结GC B细胞中衰老细胞的积累都会随着年龄的增长而增加。此外，对同一批小鼠进行的终生纵向研究表明，口腔微生物群的组成存在与年龄相关的同步变化，同时唾液IgA分泌减少。进一步对移植了野生型或p16和p21双敲除小鼠B细胞的Rag1小鼠进行的研究表明，B细胞衰老会导致IgA分泌减少和口腔微生物群改变。这些发现加深了我们对口腔微生物群与年龄相关变化机制的理解，并为控制这些变化开辟了可能性。
