Mytho, An Uncharacterized Gene that Controls Longevity and WIPI2-dependent Autophagy

The identification of genes that confer either extension of life span or accelerate age-related decline was a step forward in our understanding the mechanisms of senescence and revealed that aging process is partially controlled by genetics and transcriptional programs. Here we identified that the unknown DNA sequence c16orf70 encodes for a protein, named Mytho, that controls life span. Mytho is conserved from worms to humans and is upregulated in aged mice and elderly people. Deletion of the ortholog Mytho gene in C. elegans dramatically shortened life-span and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy because it acts as scaffold to recruit and assemble the conjugation system at the phagophore assembly site (PAS). We conclude that Mytho is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance to ensure organism longevity.