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Nat. Commun., Jan 02 2024, 15 (1) | https://doi.org/10.1038/s41467-023-44263-2 Mucosal TLR5 activation controls healthspan and longevity

Jae Sung Lim ^#,1,2, Eun Jae Jeon ^{# 3}, Hye Sun Go ³, Hyung-Jin Kim ³, Kye Young Kim ³, Thi Quynh Trang Nguyen ^1,4, Da Young Lee ^1,4, Kyu Suk Kim ¹, Federico Pietrocola⁵, Seol Hee Hong ⁶, Shee Eun Lee ⁶, Kyoung-Shim Kim ⁷, Tae-Shin Park ⁷, Dong-Hee Choi ⁷, Yu-Jin Jeong ⁸, Jong-Hwan Park ⁸, Hyeon Sik Kim ⁹, Jung-Joon Min ¹⁰, Yong Sook Kim ¹¹, Joon Tae Park ¹², Jae-Ho Cho ¹³, Gil-Woo Lee¹³, Ji Hyeon Lee ¹⁴, Hyon E Choy ¹⁵, Sang Chul Park ¹⁶, Chul-Ho Lee ^17,*, Joon Haeng Rhee ^18,19,20,*, Manuel Serrano ^21,22,*, Kyung A Cho ^{23,24,25,26,*}

¹Department of Biochemistry, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

²College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea.

³MediSpan, Inc, Bundang-gu, Gyeonggi-do, 13486, Republic of Korea.

⁴Center for Creative Biomedical Scientists, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

⁵Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.

⁶Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea.

⁷Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.

⁸Department of Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Republic of Korea.

⁹Medical Photonic Research Center, Korea Photonics Technology Institute, Gwangju, 61007, Republic of Korea.

¹⁰Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

¹¹Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea.

¹²Department of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea.

¹³Combinatorial Tumor Immunotherapy Medical Research Center, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

¹⁴Department of Biological Sciences and Bioengineering, Inha University, Incheon, 22212, Republic of Korea.

¹⁵Department of Microbiology, Chonnam National University Medical School, 264 Seoyang-ro, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

¹⁶Future Life and Society Research Center, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

¹⁷Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.

¹⁸Center for Creative Biomedical Scientists, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

¹⁹Combinatorial Tumor Immunotherapy Medical Research Center, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

²⁰Department of Microbiology, Chonnam National University Medical School, 264 Seoyang-ro, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

²¹Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.

²²Altos Labs, Cambridge Institute of Science, Cambridge, UK.

²³Department of Biochemistry, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

²⁴MediSpan, Inc, Bundang-gu, Gyeonggi-do, 13486, Republic of Korea.

²⁵Center for Creative Biomedical Scientists, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

²⁶Future Life and Society Research Center, Chonnam National University Medical School, Hwasun-gun, Jeonnam-do, 58128, Republic of Korea.

^#Contributed equally.
^*Corresponding authors: correspondence to Chul-Ho Lee, Joon Haeng Rhee, Manuel Serrano or Kyung A Cho

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.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-05)
연구진국내(교신)+국외 연구진
분야 생명과학 > 노화/암생물학

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