AANAT-KO Mouse Model for Physiologically Relevant Accelerated Aging

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Solution Overview

Problem

There are currently no non-human animal models of accelerated healthy aging, and existing animal models for accelerated aging are based on aging diseases, exhibiting disease phenotypes unrelated to healthy aging.

Innovation Solution

Development of non-human animal models, such as mice, with reduced or eliminated levels of aralkylamine N-acetyltransferase (AANAT) polypeptide expression, achieved through genetic disruptions, which mimic accelerated aging via a physiologically relevant mechanism, including reduced melatonin synthesis, increased cytosolic mtDNA release, and activation of the cGAS/STING/IRF3 pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing animal models for accelerated aging are used, then aging phenotypes can be studied, but the models exhibit disease phenotypes unrelated to healthy aging

Engineering Contradiction:

Improverelevance to healthy agingVSAvoiddisease phenotype coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the physiological parameter of melatonin synthesis by disrupting the AANAT gene, creating a model that mimics age-related melatonin decline without introducing disease mutations. This parameter change produces accelerated aging phenotypes that are physiologically relevant rather than disease-specific

Inventive Principle:

Principle #35Parameter changes

2Reliability

If AANAT gene disruption is introduced to reduce melatonin synthesis, then accelerated aging features are recapitulated, but genetic modification complexity increases

Engineering Contradiction:

Improvephysiologically relevant aging mechanismVSAvoidgenetic engineering complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and removes the AANAT gene function through disruption, eliminating melatonin synthesis capability. This extraction approach creates a simplified genetic model that focuses on a single physiological parameter (melatonin levels) while producing complex aging phenotypes

Inventive Principle:

Principle #2Taking out (Extraction)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The AANAT-KO mouse model recapitulates features of accelerated aging and neurodegeneration, providing a valuable tool for screening and validating therapeutic interventions for aging-related conditions.

Implementation Method 1

mice having the AANAT gene knocked out by designing CRISPR/Cas9 vectors against the AANAT gene

Methodology Applied

Scientific EffectCRISPR/Cas9 gene editing:

Implementation Method 2

melatonin can modulate cytosolic mtDNA release

Methodology Applied

Scientific EffectMelatonin modulation of mtDNA release:

Implementation Method 3

activation of the cGAS pathway, and pathologic inflammatory response

Methodology Applied

Scientific EffectcGAS pathway activation:

Data Source

PatentUS12543712B2Genetically modified mouse with a disruption in an AANAT gene

Publication Date: 2026.02.10 UNIV OF PITTSBURGH OF THE COMMONWEALTH SYST OF HIGHER EDUCATION

AI summary

This document relates to non-human animal models (e.g., non-human mammalian models such as mouse models) for aging (e.g., neural aging). For example, non-human animal models having reduced or eliminated levels of aralkylamine N-acetyltransferase (AANAT) polypeptide expression are provided.