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C16ORF70/MYTHO promotes healthy aging in C.elegans and prevents cellular senescence in mammals.

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 Bj Jefferies | Ivan Dikic | Jennifer van der Laan | Filipe Cabreiro | Douglas P Millay | Sharon A Tooze | Eva Trevisson | Marco Sandri
The Journal of clinical investigation | 2024

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.

Pubmed ID: 38869949

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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Eukaryotic Linear Motif (tool)

RRID:SCR_003085

Computational biology resource for investigating candidate functional sites in eukarytic proteins. Functional sites which fit to the description linear motif are currently specified as patterns using Regular Expression rules. To improve the predictive power, context-based rules and logical filters are being developed and applied to reduce the amount of false positives. The current version of the ELM server provides core functionality including filtering by cell compartment, phylogeny, globular domain clash (using the SMART/Pfam databases) and structure. In addition, both the known ELM instances and any positionally conserved matches in sequences similar to ELM instance sequences are identified and displayed (see ELM instance mapper). Although the ELM resource contains a large collection of functional site motifs, the current set of motifs is not exhaustive.

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PROGENY (tool)

RRID:SCR_006647

Fully customizable, comprehensive genetic pedigree and clinical data management software including a multi-user relational database with an integrated pedigree drawing component to manage genetic and pedigree data in one database. Manage Pedigrees, Individuals, SNPs, STRs, Samples, Plates, Genotypes and exports to multiple analysis platforms. (entry from Genetic Analysis Software) * LIMS software, providing advanced sample tracking and management (including functionality to generate and record barcodes) and configurable workflows for your specific environment. * Full genotype management gives users the ability to track not only family-based studies, but Whole Genome Association studies containing 1000''s of samples with large arrays.

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Bio-Rad Laboratories (tool)

RRID:SCR_008426

Commercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.

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Program to Reduce Incontinence by Diet and Exercise (tool)

RRID:SCR_009018

Randomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

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Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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PS6936 (tool)

RRID:WB-STRAIN:WBStrain00030987

Caenorhabditis elegans with name syIs321 I. from WB.

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MAH215 (organism)

RRID:WB-STRAIN:WBStrain00026452

Caenorhabditis elegans with name sqIs11. from WB.

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DA1116 (organism)

RRID:WB-STRAIN:WBStrain00005548

Caenorhabditis elegans with name eat-2(ad1116) II. from WB.

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DH26 (organism)

RRID:WB-STRAIN:WBStrain00005805

Caenorhabditis elegans with name rrf-3(b26) II. from WB.

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CB4037 (organism)

RRID:WB-STRAIN:WBStrain00004531

Caenorhabditis elegans with name glp-1(e2141) from WB.

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DA2123 (organism)

RRID:WB-STRAIN:WBStrain00005592

Caenorhabditis elegans with name adIs2122 from WB.

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N2 (organism)

RRID:WB-STRAIN:WBStrain00000001

Caenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.

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CB1370 (organism)

RRID:WB-STRAIN:WBStrain00004309

Caenorhabditis elegans with name daf-2(e1370) from WB.

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