Novel Animal Model for High-Throughput Screening of Anti-Aging and Metabolic Disease Drugs

This invention is a novel, in vivo, luciferase-based reporter animal model that provides a dynamic, quantifiable measure of methionine metabolism in living organisms. This scalable, semi-high-throughput system enables the rapid and cost-effective identification of pharmacological mimetics for dietary methionine restriction, which can extend lifespan and improve health span.

Description

The core of this technology is an engineered in vivo animal model that functionally reports methionine metabolism through a genetic luciferase system. This model links a regulatory element of a key gene involved in methionine metabolism to a luciferase gene, so that the gene's expression is driven by methionine availability. This unique configuration translates the organism's methionine flux into a quantifiable bioluminescent signal, offering a functional, physiologically relevant readout. Unlike costly, low-throughput metabolomic techniques like LC/MS, this animal model provides a sensitive, selective, and semi-high-throughput alternative suitable for drug discovery. The model has been validated under various dietary, genetic, and pharmacological manipulations, including a proof-of-principle demonstration using commercially available inhibitors of the methionine metabolism pathway.

Applications

- Aging Research: Screening for novel compounds that mimic the health- and lifespan-extending benefits of dietary methionine restriction (MetR).
- Metabolic Disease Research: Developing pharmacological interventions for chronic diseases where excessive methionine intake is a risk factor, such as cardiovascular disease and neurodegeneration.
- Drug Discovery and Development: Utilizing the platform for screening existing FDA-approved drugs to repurpose them as MetR mimetics.

Advantages

- Physiologically Relevant Readout: Offers a functional, in vivo measurement that captures the biological effects of methionine metabolism dynamically, unlike endpoint quantification methods.
- Semi-High-Throughput Screening: Provides a scalable and cost-effective platform for rapidly screening FDA-approved drugs to identify pharmacological mimetics.
- Non-Destructive & Longitudinal Studies: Enables repeated measurements in the same living organism, facilitating time-course studies that are not possible with traditional assays.
- High Specificity and Sensitivity: The model design ensures a responsive and selective signal specifically for changes in methionine availability while minimizing off-target signals from other amino acids.

Invention Readiness

The technology is defined by an existing model that has been successfully validated with in vivo data. The model's performance has been demonstrated by showing a significant reduction in reporter activity when inhibiting a rate-limiting enzyme in the methionine metabolism pathway. The design is already suited for the intended use of screening compounds, specifically for identifying pharmacological mimetics of methionine restriction.

IP Status

Research Tool

Related Publication(s)

Parkhitko, A. A., Pathak, S., Johnson, J. E., Mittendorfer, B., & Steinhauser, M. L. (2025). Methionine restriction and mimetics to ameliorate human aging and disease. Trends in Endocrinology & Metabolism. https://doi.org/10.1016/j.tem.2025.09.006