title: One-carbon metabolism: an aging-cancer crossroad for the gerosuppressant metformin.
abstract: The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK. If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including cancer, unraveling new proximal causes through which AMPK activation endows its gerosuppressive effects may offer not only a better understanding of metformin function but also the likely possibility of repositioning our existing gerosuppressant drugs. Here we provide our perspective on recent findings suggesting that de novo biosynthesis of purine nucleotides, which is based on the metabolism of one-carbon compounds, is a new target for metformin's actions at the crossroads of aging and cancer.
authors.affiliation: Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology-Girona (ICO-Girona), Girona, Spain. mccubreyj@ecu.edu
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002244:Carbon / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D020536:Enzyme Activators; D002244:Carbon; D008687:Metformin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D055372:AMP-Activated Protein Kinases