Dissecting primary and secondary senescence to enable new senotherapeutic strategies

• There is no universal gene expression signature for senescent cells or the SASP. Primary and secondary seem to be distinct from each other in some respects. Secondary senescence can spread via secreted molecules, extracellular vesicles, cell-to-cell contact. contributes accumulation of associated with diseases aging. Cellular a state stable cell cycle arrest that known elicited response different stresses forms damage. Senescence limits replication old, damaged, precancerous short-term but implicated debilities aging due loss regenerative reserve secretion complex combination factors called senescence-associated secretory phenotype (SASP). More recently, investigators have discovered induced by these methods (what we term “primary cells”) are also capable inducing non-senescent undergo — phenomenon call “secondary senescence.” has been demonstrated occur two broad types mechanisms. First, SASP shown involved spreading senescence; this “paracrine Second, primary induce an additional group mechanisms involving contacts types; “juxtacrine “Secondary senescence” our definition thus overarching both paracrine juxtacrine together. By allowing inherently small number incapable increase possibly anatomically distant locations, allows initially contribute further age-related pathologies. We propose understanding how differ their will enable development new rejuvenation therapies target populations interrupt spread, extending human health- potentially lifespan.