| Professor | Shimpei KAWAMOTO |
Unveiling the Essence of Aging through the Crosstalk between the Microbiome, Immune System, and Cellular Senescence
Our laboratory is dedicated to elucidating the detailed mechanisms by which the human microbiome influences the aging process via the immune system. We perceive aging as a complex outcome of the tripartite interaction between the microbiome, the immune system, and cellular senescence.
Emerging evidence suggests that age-related dysbiosis—the disruption of microbial balance—not only destabilizes immune homeostasis but also promotes the accumulation of senescent cells. These cells, in turn, accelerate systemic aging by inducing chronic inflammation through the Senescence-Associated Secretory Phenotype (SASP). Focusing on major symbiotic sites including the intestinal tract, oral cavity, and skin, we employ multifaceted approaches to analyze how microbial shifts trigger immunosenescence and cellular senescence, ultimately leading to the decline of tissue function.
1. Gut Microbiota: We investigate its role as a “master regulator” that governs systemic immune balance and modulates the clearance or accumulation of senescent cells.
2. Oral Microbiota: We explore the pathological links through which the systemic dissemination of chronic inflammation triggers cellular senescence in remote tissues and contributes to age-related diseases.
3. Skin Microbiota: Utilizing the skin—the primary interface with the external environment—as a model, we identify the molecular mechanisms by which symbiotic bacteria directly intervene in cellular senescence.
By deciphering the mechanisms that control these complex crosstalks, we aim to contribute to the development of novel interventions for extending healthy life expectancy.
Ultimate Goal: Extending healthy life expectancy by modulating the microbiome and the immune system.
Research Topics
・Elucidating the mechanisms of B-cell senescence induction by the gut microbiota
・Elucidating the induction of chronic inflammation (inflammaging) via T-cell alteration driven by the gut microbiota and its impact on tissue aging
・Deciphering the mechanisms of skin aging driven by the crosstalk between skin bacteria, the immune system, and cellular senescence
Selected Publications
1. † Kawamoto S, Horiguchi H, Torigoe D, Wakita M, Ito K, Sugawara S, Zhou X, Mikawa T, Park JH, Jung BK, Okumura Y, Miyagawa H, Maruya M, Hori N, Uemura K, Sugimoto M, Matsuda M, Mochizuki N, Kondoh H, Takahashi A, Oike Y, †Hara E. Reevaluating the senolytic activity of a GLS1 inhibitor and an anti-PD-1 antibody: toward greater reproducibility and methodological rigor. EMBO Rep., 2026; Online ahead of print. (†corresponding author)
2. Mizuno H, † Kawamoto S, Uemura K, Park JH, Hori N, Okumura Y, Konishi Y, †Hara E. B cell senescence promotes age-related changes in oral microbiota. Aging Cell, 2024;23(12): e14304. (†corresponding author)
3. † Kawamoto S, Hara E. Crosstalk between gut microbiota and cellular senescence: a vicious cycle leading to aging gut. Trends Cell Biol. 2024;34(8):626-635. (†corresponding author)
4. Matsudaira T, Nakano S, Konishi Y, Kawamoto S, Uemura K, Kondo T, Sakurai K, Ozawa T, Hikida T, Komine O, Yamanaka K, Fujita Y, Yamashita T, Matsumoto T, Hara E. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Commun. Biol. 2023;6:665.
5. † Kawamoto S, Uemura K, Hori N, Takayasu L, Konishi Y, Katoh K, Matsumoto T, Suzuki M, Sakai Y, Matsudaira T, Adachi T, Ohtani N, Standley DM, Suda W, Fukuda S, †Hara E. Bacterial induction of B cell senescence promotes age-related changes in the gut microbiota. Nat. Cell Biol. 2023;25(6):865-876. (†corresponding author)
Research Interests
Microbiome, Immune system, Cellular senescence, Aging