SAM, SAH and C. elegans longevity: insights from a partial AHCY deficiency model

Supplementation with S-adenosylhomocysteine (SAH) extends the lifespan of model organisms. To explore the impact of SAH on aging, we generated a Caenorhabditis elegans model by introducing the S-adenosylhomocysteine hydrolase (AHCY-1) variant Y145C, corresponding to the human AHCY Y143C pathogenic mutation. This mutation is anticipated to impair SAH hydrolysis, resulting in its increased levels. Our findings revealed that animals with this endogenous mutation exhibited delayed aging, accompanied by decreased S-adenosylmethionine (SAM) and moderately increased SAH levels. The extended lifespan of these worms depends on the AMP-activated protein kinase (AMPK), its activator Vaccinia virus-related kinase (VRK-1), and the DAF-16 transcription factor. The results underline the complex nature of SAH's influence on aging, proposing that the balance between SAM and SAH might play a pivotal role in defining the lifespan of C. elegans. Moreover, our partial AHCY-1 deficiency model offers a tool for studying the intersection of methionine metabolism and aging.

Automated summary

Supplementation with S-adenosylhomocysteine (SAH) can extend the lifespan of model organisms. This study generated a Caenorhabditis elegans model with a mutation in S-adenosylhomocysteine hydrolase (AHCY-1), resulting in delayed aging. The balance between S-adenosylmethionine (SAM) and SAH appears to play a pivotal role in defining the lifespan of C. elegans.