In-vivo screening implicates endoribonuclease Regnase-1 in modulating senescence-associated lysosomal changes

Richard Venz, Anita Goyala, Abel Soto-Gamez, Tugce Yenice, Marco Demaria, Collin Y Ewald*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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Accumulation of senescent cells accelerates aging and age-related diseases, whereas preventing this accumulation extends the lifespan in mice. A characteristic of senescent cells is increased staining with β-galactosidase (β-gal) ex vivo. Here, we describe a progressive accumulation of β-gal staining in the model organism C. elegans during aging. We show that distinct pharmacological and genetic interventions targeting the mitochondria and the mTORC1 to the nuclear core complex axis, the non-canonical apoptotic, and lysosomal-autophagy pathways slow the age-dependent accumulation of β-gal. We identify a novel gene, rege-1/Regnase-1/ZC3H12A/MCPIP1, modulating β-gal staining via the transcription factor ets-4/SPDEF. We demonstrate that knocking down Regnase-1 in human cell culture prevents senescence-associated β-gal accumulation. Our data provide a screening pipeline to identify genes and drugs modulating senescence-associated lysosomal phenotypes.

Originele taal-2English
StatusE-pub ahead of print - 29-aug.-2023

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