Nature Communications (Jan 2024)
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,
- Kyung A Cho
Affiliations
- Jae Sung Lim
- Department of Biochemistry, 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
- Department of Biochemistry, Chonnam National University Medical School
- Da Young Lee
- Department of Biochemistry, Chonnam National University Medical School
- Kyu Suk Kim
- Department of Biochemistry, Chonnam National University Medical School
- Federico Pietrocola
- Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Catalan Institution for Research and Advanced Studies (ICREA)
- Seol Hee Hong
- Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University
- Shee Eun Lee
- Department of Pharmacology and Dental Therapeutics, School of Dentistry, 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
- Department of Animal Medicine, College of Veterinary Medicine, Chonnam National University
- Jong-Hwan Park
- Department of Animal Medicine, College of Veterinary Medicine, Chonnam National University
- Hyeon Sik Kim
- Medical Photonic Research Center, Korea Photonics Technology Institute
- Jung-Joon Min
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital
- Yong Sook Kim
- Biomedical Research Institute, Chonnam National University Hospital
- Joon Tae Park
- Department of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University
- Jae-Ho Cho
- Combinatorial Tumor Immunotherapy Medical Research Center, Chonnam National University Medical School
- Gil-Woo Lee
- Combinatorial Tumor Immunotherapy Medical Research Center, Chonnam National University Medical School
- Ji Hyeon Lee
- Department of Biological Sciences and Bioengineering, Inha University
- Hyon E. Choy
- Department of Microbiology, Chonnam National University Medical School
- Sang Chul Park
- Future Life and Society Research Center, Chonnam National University Medical School
- Chul-Ho Lee
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)
- Joon Haeng Rhee
- Center for Creative Biomedical Scientists, Chonnam National University Medical School
- Manuel Serrano
- Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Catalan Institution for Research and Advanced Studies (ICREA)
- Kyung A Cho
- Department of Biochemistry, Chonnam National University Medical School
- DOI
- https://doi.org/10.1038/s41467-023-44263-2
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
