C16ORF70/Mytho promotes healthy aging in C. elegans and prevents cellular senescence in mammals
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Anais Franco-Romero Valeria Morbidoni Giulia Milan Roberta Sartori Jesper Wulff Vanina Romanello Andrea Armani Leonardo Salviati Maria Conte Stefano Salvioli Claudio Franceschi Viviana Buonomo Casey O Swoboda Paolo Grumati Luca Pannone Simone Martinelli Harold Jefferies Ivan Dikic Jennifer Van der Laan Filipe Cabreiro Douglas P Millay Sharon Tooze Eva Trevisson Marco SandriAbstract
The identification of genes that confer either extension of lifespan or accelerate age-related decline was a step forward in understanding the mechanisms of ageing and revealed that it is partially controlled by genetics and transcriptional programs. Here we discovered that the human DNA sequence C16ORF70 encoded for a protein, named MYTHO (Macroautophagy and YouTH Optimizer), which controls life- and health-span. MYTHO protein is conserved from C. elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the ortholog myt-1 gene in C. elegans dramatically shortened lifespan and decreased animal survival upon exposure to oxidative stress. Mechanistically, MYTHO is required for autophagy likely because it acts as a scaffold that binds WIPI2 and BCAS3 to recruit and assemble the conjugation system at the phagophore, the nascent autophagosome. We conclude that MYTHO is a transcriptionally regulated initiator of autophagy that is central in promoting stress resistance and healthy ageing.
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Volume
134
Issue number
15
Pages
e165814
Available online
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10.1172/JCI165814
Europe PubMed Central
38869949
Pubmed
38869949
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