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Mucosal TLR5 activation controls healthspan and longevity.

Jae Sung LimEun Jae JeonHye Sun GoHyung-Jin KimKye Young KimThi Quynh Trang NguyenDa Young LeeKyu Suk KimFederico PietrocolaSeol Hee HongShee Eun LeeKyoung-Shim KimTae-Shin ParkDong-Hee ChoiYu-Jin JeongJong-Hwan ParkHyeon Sik KimJung-Joon MinYong Sook KimJoon Tae ParkJae-Ho ChoGil-Woo LeeJi Hyeon LeeHyon E ChoySang Chul ParkChul-Ho LeeJoon-Haeng RheeManuel SerranoKyung A Cho
Published in: Nature communications (2024)
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.
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