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enescence is a stress response that preserves tissue homeostasis by preventing the replication of old, preneoplastic or damaged cells 1 . Senescent cells undergo a stable cell-cycle arrest and display profound changes in nuclear and chromatin organization, gene expression, cell metabolism and secretory profile 2 . Depending on the physiological context, senescence can be either beneficial or detrimental. Induction of senescence can restrain tumor progression 3 and limit fibrosis 4 ; however, the aberrant accumulation of senescent cells contributes to aging and age-related pathologies 5 . Moreover, there is now strong evidence that the selective elimination of senescent cells delays the onset of age-related diseases or at least ameliorates their symptoms 6 . Given the causative role of senescence in the aging process and its contribution to multiple age-related diseases, senescent cells are prime targets for drug-induced elimination (senolysis) 7 , but alternative strategies are also pursued. One such strategy is rejuvenating senescent cells 8,9 .The two defining hallmarks of senescent cells are a stable cellcycle arrest (mediated by the transcriptional upregulation of cyclindependent kinase inhibitors such as p16 INK4a ) and the secretion of a complex combination of factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The SASP is widely believed to mediate many of the detrimental effects exerted by senescent cells and consequently, strategies have been devised to target it 10,11 . A progressive induction of senescence, especially in adult stem cell populations has been associated with age-dependent declines in tissue function 12,13 . With age, stem cell populations undergo senescence and, as a result, the ability of the tissue to repair after damage gradually diminishes 14 . Consequently, strategies aimed at alleviating stem cell senescence have the potential to preserve the regenerative potential in aged tissues. As cellular senescence is one of the main impasses for the expansion of stem cells ex vivo, drugs that prevent the onset of senescence could also be used to optimize the generation of stem cells for subsequent cellular therapies.We have previously performed high-throughput drug screens to identify cardiac glycosides as broad-spectrum senolytics 15 . Here, we followed a similar approach to identify drugs alleviating senescence. We found that treatment with 3DA, an S-adenosyl homocysteinase (AHCY) inhibitor 16,17 , partially prevents both replicative and oncogene-induced senescence. We confirmed the potential benefits of 3DA treatment in ex vivo cultures and engraftment experiments of

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A series of 4-aroyl-1H-benzo[c]oxepin-4-ones have been prepared by heating ethyl 2-aroyl-3-(2-bromophenyl)propenoates. The synthesized compounds possess higher analgesic activity than the reference drug (analgin) and exhibit low toxicity.

Supplementary Figure 2 from Global Reactivation of Epigenetically Silenced Genes in Prostate Cancer