The persistent dynamic secrets of senescence.

While the beneficial versus detrimental implications of the senescence-associated secretome remain an issue of debate, time-resolved analyses of its composition, regulatory mechanisms and functional consequences have been largely missing. The dynamic activity of NOTCH is now shown to direct two distinct senescence phenotypes, by first promoting a pro-senescent TGF-β1-dependent secretome, followed by a second wave of pro-inflammatory, senescence-clearing cytokines.