Nutrient sensing, calorie restriction, and drugs such as rapamycin and metformin.
Mice on a 30% calorie-restricted diet had up to 39% fewer new mutations in their liver cells by old age. Oddly, the protection was strongest in the parts of the genome cells don’t use much.
Animal study
Metformin is thought to work partly through an energy sensor called AMPK, but it does many other things too. A compound that switches AMPK on directly extended lifespan in three species, and only when AMPK was there to switch on.
Animal study
The Long Run