Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders

Abstract

Selective destruction of senescent cells Senescent cells are associated with a variety of age-related medical conditions and thus have been proposed as potential targets for therapy, but we do not yet have a full understanding of the underlying mechanisms. Johmura et al. used RNA interference to screen for enzymes essential to the survival of senescent cells (see the Perspective by Pan and Locasale). The authors identified a key role for glutamine metabolism, particularly the enzyme glutaminase 1, and demonstrated that inhibition of this pathway induced the death of senescent cells. Glutaminase targeting also ameliorated aging-related organ dysfunction and obesity-related disorders in mouse models, suggesting the potential therapeutic value of this approach. Science , this issue p. 265 ; see also p. 234