Theaflavin-regulated Imd condensates control Drosophila intestinal homeostasis and aging

Abstract

Summary Black tea is the most widely consumed tea drink in the world and has consistently been reported to possess anti-aging benefits. However, whether theaflavins, one type of the characteristic phytochemicals in black tea extracts, are involved in regulating aging and lifespan in consumers remains largely unknown. In this study, we show that theaflavins play a beneficial role in preventing age-onset intestinal leakage and dysbiosis, thus delaying aging in Drosophila . Mechanistically, theaflavins regulate the condensate assembly of Imd to negatively govern the overactivation of Imd signals in fruit fly intestines. In addition, theaflavins prevent DSS-induced colitis in mice, suggesting theaflavins play a role in modulating intestinal integrity. Overall, our study reveals a molecular mechanism by which theaflavins regulate gut homeostasis likely through controlling Imd coalescence.

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

“…Flavonoid compounds are divided into six subclasses, flavones, flavonols, flavanones, isoflavones, flavanols, and anthocyanins [ 228 ]. Beside the antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, which make them of great interest as anti-aging compounds ( Table 3 ) [ 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 , 256 , 257 ].…”

A Feedback Regulatory Loop Involving dTrbd/dTak1 in Controlling IMD Signaling in Drosophila Melanogaster

“…However, the mRNA levels of these AMP genes were relatively comparable between samples from c564 ts >GFP-dTrbd DNZF , c564 ts >GFP-dTrbd DLR , and the control flies (Figures 5A, B), suggesting both the NZF domain and the LR are required for dTrbd to negatively govern IMD signaling post microbial infection. Previous studies have shown that preventing the IMD signaling pathway in gut tissues positively contributes to the life longevity of Drosophila (15,(41)(42)(43). We thus sought to identify whether dTrbd modulates lifespan via multiple domains.…”

Flavonoids—Natural Gifts to Promote Health and Longevity

“…Studies have shown that theaflavin can delay the excessive proliferation of intestinal stem cells, prevent intestinal dysbiosis, and inhibit the activation of the Imd signaling pathway, thereby prolonging the lifespan of Drosophila. At the same time, theaflavin is effective in preventing DSS-induced colitis in mice [73]. Moreover, theaflavin can protect against oxidative stress-induced cellular senescence by activating Nrf2 in a mouse osteoarthritis model [85].…”