Dual pharmacological targeting of coactivator-associated arginine methyltransferase 1 (CARM1) and salt inducible kinase (SIK) drives ketogenesis in both hepatocytes and mice.

Tábata Bergonci, Troels Kjær Rosenbæk, Samuel J Windross, Ulrik B Keiding, Estéfano Pinilla, Katrine P Stuckert, Jakob Hansen, Camilla B Nielsen, Jemila Peter Gomes, Lucy R Davies, Johan Palmfeldt, Volker Loeschcke, Charlotte U Andersen, Ulf Simonsen, Thomas B Poulsen, Mogens Johannsen

Department of Forensic Medicine, Aarhus University, Aarhus, Denmark.Department of Forensic Medicine, Aarhus University, Aarhus, Denmark. · pubmed

Paper

Abstract

Ketone bodies are liver-derived circulating energy metabolites that positively impact most hallmarks of ageing. Ketone bodies increase during calorie restriction and fasting, two of the more widely perceived methods to increase health span. Adhering to a strict diet to increase ketogenesis is demanding, which leaves a significant unmet need for a pharmacological alternative. The present study hypothesised that chemical genetic screening can reveal novel proteins that will regulate ketogenesis.

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Research summary

The study claims that dual pharmacological targeting of CARM1 and SIK can enhance ketogenesis in hepatocytes and mice. This research is relevant as it explores pharmacological interventions that could potentially mimic the effects of calorie restriction and fasting, which are associated with increased health span and longevity.

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