Mucosal TLR5 activation controls healthspan and longevity

Jae Sung Lim, Eun Jae Jeon, Hye Sun Go, Hyung-Jin Kim, Kye Young Kim, Thi Quynh Trang Nguyen, Da Young Lee, Kyu Suk Kim, Federico Pietrocola, Seol Hee Hong, Shee Eun Lee, Kyoung-Shim Kim, Tae-Shin Park, Dong-Hee Choi, Yu-Jin Jeong, Jong-Hwan Park, Hyeon Sik Kim, Jung-Joon Min, Yong Sook Kim, Joon Tae Park, Jae-Ho Cho, Gil-Woo Lee, Ji Hyeon Lee, Hyon E. Choy, Sang Chul Park, Chul-Ho Lee (), Joon Haeng Rhee (), Manuel Serrano () and Kyung A Cho ()
Additional contact information
Jae Sung Lim: Chonnam National University Medical School
Eun Jae Jeon: MediSpan, Inc
Hye Sun Go: MediSpan, Inc
Hyung-Jin Kim: MediSpan, Inc
Kye Young Kim: MediSpan, Inc
Thi Quynh Trang Nguyen: Chonnam National University Medical School
Da Young Lee: Chonnam National University Medical School
Kyu Suk Kim: Chonnam National University Medical School
Federico Pietrocola: Catalan Institution for Research and Advanced Studies (ICREA)
Seol Hee Hong: Chonnam National University
Shee Eun Lee: Chonnam National University
Kyoung-Shim Kim: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Tae-Shin Park: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Dong-Hee Choi: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Yu-Jin Jeong: Chonnam National University
Jong-Hwan Park: Chonnam National University
Hyeon Sik Kim: Medical Photonic Research Center, Korea Photonics Technology Institute
Jung-Joon Min: Chonnam National University Hwasun Hospital
Yong Sook Kim: Biomedical Research Institute, Chonnam National University Hospital
Joon Tae Park: Incheon National University
Jae-Ho Cho: Chonnam National University Medical School
Gil-Woo Lee: Chonnam National University Medical School
Ji Hyeon Lee: Inha University
Hyon E. Choy: Chonnam National University Medical School
Sang Chul Park: Chonnam National University Medical School
Chul-Ho Lee: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Joon Haeng Rhee: Chonnam National University Medical School
Manuel Serrano: Catalan Institution for Research and Advanced Studies (ICREA)
Kyung A Cho: Chonnam National University Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Date: 2024
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DOI: 10.1038/s41467-023-44263-2

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