In addition to influenza vaccines, recently, it has been reported that the effectiveness of vaccines against infections such as COVID-19 is reduced in the elderly. Impaired functions of innate immunity can further exacerbate the flaws in adaptive immunity, for instance, by not providing efficient antigen presentation to T cells 6. Aging-dependent deterioration of innate immune cells includes the reduction in phagocytic activity, ROS generation, and reduction of pathogen recognition receptors (PRRs) expression, failing to defend against various infections and respond to vaccines 5. The effects of aging on the immune system appear at various levels, including decreased production of immune cells in the bone marrow and thymus, reduced function of mature lymphocytes in secondary lymphoid tissue, and decreased function of innate immune cells in various tissues 4. ![]() Such alterations may contribute to the development of metabolic and cardiovascular diseases, neurodegenerative syndromes, and age-related ailments such as frailty 1, 2, 3. Similar content being viewed by othersĪge-associated immunological alterations are multifaced and include enhanced susceptibility to infection and chronic tissue inflammation. 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. 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. 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. 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. ![]() Nature Communications volume 15, Article number: 46 ( 2024)Īddressing 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. Mucosal TLR5 activation controls healthspan and longevity
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