Dual pharmacological targeting of coactivator-associated arginine methyltransferase 1 (CARM1) and salt inducible kinase (SIK) drives ketogenesis in both hepatocytes and mice.
Targeting a specific protein axis triggered sustained calorie-restriction-like metabolic changes in human cells without harming blood sugar control.
Using phenotypic screening, this study identifies CARM1 as a novel regulator of ketogenesis and shows that simultaneously inhibiting/activating CARM1 and SIK produces a synergistic ketogenic response in human hepatocytes and mice without perturbing blood glucose. These findings nominate the CARM1/SIK axis as a druggable pathway for pharmacological induction of metabolic states associated with calorie restriction-like longevity benefits.
What the study was
- Study design
- Preclinical pharmacological screen + in vitro (human hepatocytes) + in vivo (Drosophila longevity assay; mouse ketogenesis)
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- British Journal of Pharmacology
Why it surfaced
Novel CARM1/SIK dual targeting for ketogenesis in longevity context is mechanistically interesting; preclinical stage with in vivo validation in mice. Promising but far from clinical translation.
A plain-language summary of published research — not medical advice. Talk to a clinician about your own care.