PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans

Severe calorie restriction extends life-span in mice and other species, but how near-starvation can prolong life remained a mystery. Now at last, specific links between calorie restriction and longevity have been found in that workhorse of ageing research, the nematode C. elegans. Nicholas Bishop and Leonard Guarente find that dietary restriction activates transcription factor SKN-1 in ASI neurons in the head, which signal peripheral tissues to increase metabolic activity, a mechanism suggestive of the involvement of an endocrine system. Panowski et al. report that increased activity of PHA-4 (tagged green in cover image of C. elegans embryo), a transcription factor found in the intestine and in a few cells in head and tail, is also essential for diet-restricted longevity. PHA-4 resembles mammalian Foxa transcription factors, which affect development and regulate fasting glucagon and glucose levels. Knowledge of such links raises the prospect of drugs to mimic the benefits of calorie restriction.