Mucosal TLR5 Activation Controls Healthspan and Longevity

    January 2024 in “ Nature communications ”
    J. Lim, Eun Jae Jeon, Hye Sun Go, Hyungjin Kim, Kye Young Kim, Thi Quynh Trang Nguyen, D. 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
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    TLDR Activating TLR5 in the gut can extend lifespan and improve health in aged mice.
    The study demonstrates that mucosal activation of Toll-like receptor 5 (TLR5) via a flagellin-containing fusion protein (FP) significantly extends lifespan and enhances healthspan in aged mice. This intervention improved various aging-related phenotypes, such as reduced hair loss, decreased ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, enhanced cognitive function, and prevention of pulmonary fibrosis. The beneficial effects were linked to increased TLR5 expression and interleukin-22 (IL-22) secretion, which bolstered intestinal mucosal integrity. The findings suggest that TLR5-dependent mucosal stimulation could be a promising strategy for promoting healthy aging and longevity.
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