Adipose Dicer-1 modulates systemic insulin signaling and longevity via a miR-8-Aop-Dilp6 axis - PubMed
5 hours ago
- #insulin signaling
- #longevity
- #Dicer-1
- Adipose Dicer-1 (Dcr-1) modulates systemic insulin signaling and longevity via a miR-8-Aop-Dilp6 axis in Drosophila.
- Dcr-1 reduction in the fat body enhances oxidative stress resistance, alters lipid metabolism, and extends lifespan, even under dietary restriction.
- Proteomic profiling shows Dcr-1 heterozygous flies exhibit metabolic reprogramming and stress adaptation, linked to attenuated insulin/IGF signaling (IIS).
- Mechanistically, reduced Dcr-1 lowers miR-8 levels, indirectly upregulating Dilp6, which suppresses Dilp2 secretion from brain insulin-producing cells (IPCs).
- Dcr-1 reduction activates the ETS-family repressor Aop/ETV6 via Ras-Erk signaling, required for Dilp6 induction and lifespan extension.
- The study reveals a miRNA-dependent regulatory axis connecting adipose tissue to systemic insulin regulation and aging.