Mucosal TLR5 activation controls healthspan and longevity

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...

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Published in:	Nature communications 2024-01, Vol.15 (1), p.46-46, Article 46
Main Authors:	Lim, Jae Sung, Jeon, Eun Jae, Go, Hye Sun, Kim, Hyung-Jin, Kim, Kye Young, Nguyen, Thi Quynh Trang, Lee, Da Young, Kim, Kyu Suk, Pietrocola, Federico, Hong, Seol Hee, Lee, Shee Eun, Kim, Kyoung-Shim, Park, Tae-Shin, Choi, Dong-Hee, Jeong, Yu-Jin, Park, Jong-Hwan, Kim, Hyeon Sik, Min, Jung-Joon, Kim, Yong Sook, Park, Joon Tae, Cho, Jae-Ho, Lee, Gil-Woo, Lee, Ji Hyeon, Choy, Hyon E, Park, Sang Chul, Lee, Chul-Ho, Rhee, Joon Haeng, Serrano, Manuel, Cho, Kyung A
Format:	Article
Language:	eng
Subjects:	Aging Animals Bone mineral density Cognitive ability Dendritic cells Fibrosis Flagellin Flagellin - metabolism Fusion protein Homeostasis Immune system Immunology Interleukin 22 Intestinal Mucosa - metabolism Life span Longevity Longevity - genetics Lung - metabolism Lung diseases Malignancy Mice Mucosa Opacity Proteins Stem cells Therapeutic applications Thymic involution Thymus TLR5 protein Toll-Like Receptor 5 Toll-like receptors
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Summary:	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.
ISSN:	2041-1723 2041-1723