Shimpei Kawamato
Tohoku University, Japan
Bio:
Professor at the Department of Aging Biology, Institute of Development, Aging and Cancer (IDAC), and the Department of Molecular and Cellular Health Span, Health Span Research Center (HeSReC) at Tohoku University.
He received his Ph.D. from the Graduate School of Medicine, Kyoto University, in 2011 under the supervision of Professor Tasuku Honjo. During his graduate studies and subsequent postdoctoral training until 2016, he conducted research in the Laboratory for Mucosal Immunity (led by Dr. Sidonia Fagarasan) at the RIKEN Center for Integrative Medical Sciences (formerly RCAI). There, he focused on immunoglobulin A (IgA), which is abundantly secreted in the gut, and elucidated how IgA-mediated interactions between the host and gut microbiota contribute to the maintenance of biological homeostasis.
In 2016, he joined the Research Institute for Microbial Diseases (RIMD) at Osaka University as an Assistant Professor and was promoted to Associate Professor in 2023. At Osaka University, he collaborated with Professor Eiji Hara to focus on cellular senescence, successfully uncovering how the gut microbiota influences organismal aging through the modulation of immune senescence. In July 2025, he was appointed Professor at Tohoku University.
His research interests lie at the intersection of immunology, microbiology, and aging biology. Based on his unique career background, his laboratory investigates how host-gut microbiota interactions mediated by the immune system influence human health spans and the aging process.
Abstract:
The elucidation of the mechanisms of ageing and the identification of methods to control it have long been anticipated. Recently, two age-related factors—the accumulation of senescent cells and alterations in the gut microbiota composition—have been shown to play key roles in the ageing process. However, the precise mechanisms underlying these phenomena and their interrelationship during ageing remain poorly understood.
Here, using in vivo imaging with p16INK4a-reporter (p16-luc) mice maintained under specific pathogen-free (SPF) or germ-free conditions throughout their lifespan, we found that senescent cells accumulate in the ileum during ageing in a bacteria-dependent manner. Furthermore, single-cell RNA sequencing and our newly established p16INK4aimmunostaining method revealed that cellular senescence is specifically induced in germinal centre (GC) B cells within the ileum of aged mice. Given that GC B cells are critical for producing Immunoglobulin A (IgA) targeting gut bacteria, we monitored age-related changes in IgA production and gut microbiota through longitudinal analysis of individual mice. We observed a decrease in IgA production alongside significant shifts in the gut microbiota composition with age. Crucially, comparative analysis using wild-type mice and senescence-resistant mice lacking both p16INK4a and p21Waf1/Cip1genes demonstrated that B-cell senescence reduces both the production and diversity of IgA, thereby driving the alterations in the gut microbiota. Notably, Gram-negative bacteria that increase with age possessed the capacity to promote B-cell proliferation and induce cellular senescence, whereas Gram-positive bacteria that decrease with age did not. Furthermore, we extended our findings to another mucosal site and found that age-related B-cell senescence also occurs in the cervical lymph nodes. This B-cell senescence led to a reduction in salivary IgA secretion, contributing to the dysbiosis of the oral microbiota in aged mice.
These findings reveal a novel, IgA-mediated bidirectional crosstalk between the commensal microbiota and cellular senescence. Importantly, our data suggest that the reduction in IgA production and the subsequent dysbiosis of commensal microbiota driven by age-related B-cell senescence may represent a universal ageing phenomenon across the common mucosal immune system. This study deepens our understanding of the mechanisms driving age-related microbial shifts, opening up new avenues for interventions to control ageing.
