Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

TLDR

Metformin, a widely used antidiabetic drug, has been suggested to possess general health‑promoting properties. The study aims to elucidate metformin’s mode of action to expand its therapeutic use and improve aging‑related complications. Metformin extends lifespan by boosting ROS production, which activates a peroxiredoxin‑mediated signaling cascade that promotes longevity.

Abstract

Significance Recently it has been suggested that metformin, the most commonly used antidiabetic drug, might also possess general health-promoting properties. Elucidating metformin’s mode of action will vastly increase its application range and will contribute to healthy aging. We reveal a signaling cascade in which metformin is able to extend lifespan by increasing the production of reactive oxygen species (ROS). This allowed us to further work at the crossroads of human disease and aging research, identifying a key molecule that is able to translate the ROS signal into a prolongevity cue: an antioxidant peroxiredoxin is also able to activate a lifespan-promoting signaling cascade, here described in detail. Continued research efforts in this field lead toward a targeted improvement of aging-related complications.