C16ORF70/MYTHO promotes healthy aging in C.elegans and prevents cellular senescence in mammals
File(s)
Author(s)
Type
Journal Article
Abstract
The identification of genes that confer either extension of life span or accelerate age-related decline was a step forward in understanding the mechanisms of aging and revealed that it is partially controlled by genetics and transcriptional programs. Here, we discovered that the human DNA sequence C16ORF70 encodes a protein, named MYTHO (macroautophagy and youth optimizer), which controls life span and health span. MYTHO protein is conserved from Caenorhabditis elegans to humans and its mRNA was upregulated in aged mice and elderly people. Deletion of the orthologous myt-1 gene in C. elegans dramatically shortened life span 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 aging.
Date Issued
2024-08-01
Date Acceptance
2024-06-07
Citation
Journal of Clinical Investigation, 2024, 134 (15)
ISSN
0021-9738
Publisher
American Society for Clinical Investigation
Journal / Book Title
Journal of Clinical Investigation
Volume
134
Issue
15
Copyright Statement
© 2024, Franco-Romero et al. This is an open access article published
under the terms of the Creative Commons Attribution 4.0 International License.
under the terms of the Creative Commons Attribution 4.0 International License.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38869949
Subjects
Aging
Animals
Autophagy
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Cellular Senescence
Healthy Aging
Humans
Longevity
Mice
Oxidative Stress
Aging
Autophagy
Cell biology
Cellular senescence
Skeletal muscle
Publication Status
Published
Coverage Spatial
United States
Article Number
e165814
Date Publish Online
2024-06-13