Caffeine extends lifespan by enhancing lysosomal lipolysis in Caenorhabditis elegans

By using the roundworm Caenorhabditis elegans, here we show that caffeine extends lifespan by eliciting transcriptional remodeling that enhances lysosomal lipolysis. We found that transcriptomes of aged, caffeine-fed animals shifted toward youthful states.

We also showed that caffeine induced a dietary restriction (DR)-like transcriptional program. Comparison with eat-2 mutants (a genetic DR model) identified commonly upregulated genes including the lysosomal lipases lipl-1 and lipl-2. The induction of lipl-1 and lipl-2 was required for increased lifespan and reduced neutral lipid accumulation by caffeine intake.