Although cellular senescence acts primarily as a tumour suppression mechanism, the accumulation of senescent cells in vivo eventually exerts deleterious side effects through inflammatory/tumour-promoting factor secretion. Thus, the development of new drugs that cause the specific elimination of senescent cells, termed senolysis, is anticipated. Here, by an unbiased high-throughput screening of chemical compounds and a bio-functional analysis, we identify BET family protein degrader (BETd) as a promising senolytic drug. BETd provokes senolysis through two independent but integrated pathways; the attenuation of nonhomologous end joining (NHEJ), and the up-regulation of autophagic gene expression. BETd treatment eliminates senescent hepatic stellate cells in obese mouse livers, accompanied by the reduction of liver cancer development. Furthermore, the elimination of chemotherapyinduced senescent cells by BETd increases the efficacy of chemotherapy against xenograft tumours in immunocompromised mice. These results reveal the vulnerability of senescent cells and open up possibilities for its control.

Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into ApcΔ14/+ mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.

The rice blast fungus Magnaporthe oryzae differentiates a specialized infection structure called an appressorium to invade rice cells. In this report, we show that CBP1, which encodes a chitin-deacetylase, is involved in the induction phase of appressorium differentiation. We demonstrate that the enzymatic activity of Cbp1 is critical for appressorium formation. M. oryzae has six CDA homologues in addition to Cbp1, but none of these are indispensable for appressorium formation. We observed chitosan localization at the fungal cell wall using OGA488. This observation suggests that Cbp1-catalysed conversion of chitin into chitosan occurs at the cell wall of germ tubes during appressorium differentiation by M. oryzae. Taken together, our results provide evidence that the chitin deacetylase activity of Cbp1 is necessary for appressorium formation.

Root hairs, which arise from root epidermal cells, are tubular structures that increase the efficiency of water absorption and nutrient uptake. A low pH (pH 4) medium induced root hair formation in lettuce (Lactuca sativa L.) seedlings, and the decapitation of shoots inhibited root hair formation. The addition of shoot extract to the medium restored root hair formation in the decapitated lettuce seedlings. These results suggest that factors essential to the formation of root hairs may be present in the shoot. We purified one factor from the shoot that facilitates root hair formation. This factor was identified as chlorogenic acid (CGA), a common polyphenol in higher plants. The presence of exogenous CGA in the medium induced root hair formation in decapitated lettuce seedlings at pH 4.0 and in intact lettuce seedlings at pH 6.0. The optimum concentration of CGA for root hair formation was identified as 10(-5) M. Decapitation of the shoots reduced the CGA content in the roots to approximately one-third that in intact plants. Application of the CGA biosynthesis inhibitor L-alpha-aminooxy-beta-phenylpropionic acid (AOPP, 10(-6) M) to intact seedlings grown at pH 4.0 reduced both the CGA content of the roots and the total amount of root hairs. The addition of exogenous CGA restored root hair formation in intact seedlings treated with AOPP. These results suggest that CGA is essential for root hair formation in lettuce seedlings.

No abstract