Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

ABSTRACT: Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established^1,2. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1^F121A/F121A) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1 ^F121A/F121A knock-in mice in association with higher levels of basal autophagic flux. Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly incr

SUBMITTER: Fernandez AF 

PROVIDER: S-EPMC5992097 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature