Transgenic C. elegans Overexpressing Gln 5'-tsRNA for Anti-Aging

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Solution Overview

Problem

Current methods face challenges in identifying and studying anti-aging mechanisms due to the difficulty in sequencing and understanding the specific genomic origin of tRNA-derived fragments (tsRNAs), which are age-dependently changed in C. elegans, and their potential anti-aging functions remain unexplored.

Innovation Solution

Transgenic C. elegans overexpressing a glutamine tRNA 5′ end-derived fragment (Gln 5′-tsRNA) is created using a recombinant vector with a U6 promoter, exhibiting anti-aging effects through mitochondria activation and dietary restriction/AMP-dependent kinase (AMPK) pathways, allowing for the screening of aging-related factors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If tRNA-derived fragments (tsRNAs) are studied using conventional sequencing methods, then the basic presence of tsRNAs can be detected, but the exact genomic origin and specific base sequence matching remain difficult to confirm due to multiple tRNA gene copies and severe modifications in mature tRNA

Engineering Contradiction:
Improveprecision of genomic origin identificationVSAvoidcomplexity of sequencing and analysis system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces an intermediary approach by using in silico prediction models and bioinformatics tools as mediators between the sequenced tsRNA fragments and their genomic origins. Instead of directly matching modified mature tRNA sequences to genomes, the system uses computational prediction to identify potential genomic sources, thereby resolving the mismatch caused by post-transcriptional modifications.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a computational copy or model of the tRNA gene family structure and modification patterns. By building a predicted tsRNA profile based on known tRNA genes and their expected fragmentation patterns, the system can match observed tsRNAs to their genomic origins without requiring direct sequencing of modified mature tRNAs, thus overcoming the limitations of conventional sequencing methods.

Inventive Principle:
Principle #26Copying

2Productivity

If C. elegans is used as an animal model for anti-aging research, then genetic manipulation and lifespan experiments can be performed efficiently, but the specific anti-aging functions and mechanisms of tsRNAs remain unidentified

Engineering Contradiction:
Improveefficiency of lifespan experimentVSAvoidinformation on tsRNA anti-aging function
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent applies preliminary action by first identifying and characterizing tsRNA profiles at different ages in C. elegans before conducting functional experiments. The age-dependent changes in specific tsRNAs (such as Gln5'-tsRNA) are documented and predicted to have anti-aging functions, which then guides subsequent transgenic experiments to test these predictions, thereby preventing loss of critical functional information.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements feedback by using the observed age-dependent tsRNA expression patterns as feedback information to guide the design of transgenic C. elegans models. The predicted anti-aging function of specific tsRNAs is tested through lifespan experiments, and the results feed back into refining the understanding of tsRNA mechanisms, creating a continuous cycle of hypothesis testing and validation that preserves functional information.

Inventive Principle:
Principle #23Feedback

3Reliability

If transgenic C. elegans overexpressing Gln 5'-tsRNA is constructed to test anti-aging function, then lifespan can be extended and anti-aging mechanisms identified, but the complexity of constructing and validating the transgenic model increases

Engineering Contradiction:
Improvereliability of anti-aging mechanism identificationVSAvoidcomplexity of transgenic model construction
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies universality by using a standardized transgenic construction platform in C. elegans that can be applied to test multiple different tsRNAs and anti-aging hypotheses. The same basic methodology (constructing transgenic lines, measuring lifespan, analyzing mechanisms) can be universally applied to different tsRNA targets, thereby reducing the relative complexity burden for each individual study while maintaining high reliability.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS11013221B2Anti-aging transgenic Caenorhabditis elegans
Publication Date: 2021.05.25 POSTECH ACADEMY INDUSTRY FOUNDATION
  • US11013221B2 patent drawing
  • US11013221B2 patent drawing
  • US11013221B2 patent drawing

AI summary

The present invention relates to: a transgenic Caenorhabditis elegans in which a glutamine tRNA 5′ terminus-derived fragment (Gln 5′-tsRNA) is overexpressed; a preparation method therefor; and a method for screening for aging-associated factors by using the transgenic Caenorhabditis elegans. A transgenic Caenorhabditis elegans model provided in the present invention is an animal model in which Gln 5′-tsRNA is overexpressed such that aging is inhibited. When the model of the present invention is used, anti-aging mechanisms can be easily investigated, thereby significantly contributing to various research fields such as that of developing new anti-aging drugs and screening for age-inducing materials.