Causal CpG Mapping for Reliable Aging Intervention Prediction

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Solution Overview

Problem

Existing epigenetic aging clocks rely on correlations and do not establish a clear causal relationship between DNA methylation and aging-related phenotypes, making it difficult to infer the effectiveness of interventions on aging processes.

Innovation Solution

Utilize Mendelian randomization (MR) to identify causal CpG sites associated with aging-related traits, constructing causality-informed clocks that distinguish between protective and damaging epigenetic changes, and apply these to biological systems to predict the effects of interventions on aging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If correlation-based epigenetic aging clocks are used to predict age, then age prediction accuracy is improved, but the ability to establish causal relationships between DNA methylation and aging phenotypes deteriorates

Engineering Contradiction:

Improveage prediction accuracyVSAvoidcausal relationship establishment

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent uses Mendelian randomization analysis as an intermediary method to bridge the gap between correlation and causation. By introducing genetic variants as instrumental variables that influence DNA methylation patterns, the method establishes causal relationships between methylation at specific CpG sites and aging phenotypes without sacrificing the predictive accuracy of epigenetic clocks

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If all CpG sites are analyzed to build comprehensive aging clocks, then measurement coverage is improved, but the complexity of the model increases

Engineering Contradiction:

Improvenumber of CpG sites analyzedVSAvoidmodel complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent extracts and focuses on a specific subset of CpG sites that have been proven to have causal relationships with aging phenotypes through Mendelian randomization analysis. By taking out only the most relevant causal CpG sites from the entire genome, the method maintains comprehensive coverage of aging-related methylation changes while reducing model complexity and improving interpretability

Inventive Principle:

Principle #2Taking out (Extraction)

3Adaptability or versatility

If intervention effects on aging are assessed using correlation-based clocks, then assessment capability is improved, but the reliability of inferring intervention effectiveness deteriorates

Engineering Contradiction:

Improveintervention assessment capabilityVSAvoidintervention effectiveness inference

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs causality-informed clocks as an intermediary tool that incorporates causal relationships identified through Mendelian randomization. This allows for reliable assessment of intervention effects on aging by using methylation changes at causal CpG sites as biomarkers, thereby improving the reliability of inferring intervention effectiveness while maintaining the versatility of assessing various anti-aging interventions

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20260055463A1Mapping CpG Sites to Quantify Aging Traits

Publication Date: 2026.02.26 THE BRIGHAM & WOMEN S HOSPITAL INC

AI summary

Provided herein are methods that use methylation of causal CpG sites to quantify aging and predict whether an intervention will be protective or damaging to the aging process.