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A simple blood biomarker based on gene expression describes cardiovascular health-related biological age
Natalia Hernández-Bellido1,2, Adrián Hernández-Vicente3,4, Laura García-Mendívil5,6
1Biomedical Signal Interpretation and Computational Simulation (BSICoS) Group, Instituto de Investigación en Ingeniería de Aragón (I3A), Universidad de Zaragoza, Zaragoza, Spain. nhbellido@unizar.es.
Insights
A new gene expression biomarker, GamC, estimates biological age (BA) and cardiovascular health. This simple tool tracks aging beyond chronological age and responds to exercise, aiding healthy aging strategies.
Area of Science:
- Gerontology and Molecular Biology
- Biomarker Discovery
- Cardiovascular Health Research
Background:
- Chronological age (CA) is insufficient for assessing disease risk; biological age (BA) estimation is crucial for personalized health monitoring.
- Current BA tools often approximate CA or are complex, limiting clinical translation and real-time health status assessment.
- There's a need for simple, biologically relevant biomarkers to monitor aging and cardiovascular health.
Purpose of the Study:
- To introduce and characterize the gene expression-based age monitoring Clock (GamC) as a novel biomarker of aging (BOA).
- To assess GamC's biological relevance by correlating it with cardiovascular (CV) health indicators and physical activity.
- To evaluate GamC's capacity for monitoring BA changes in response to interventions.
Main Methods:
- GamC was developed using blood gene expression levels of three aging-associated genes: ABLIM1, CCR7, and LEF1.
- GamC's association with CA was validated across three independent cohorts using transcriptome-wide data.
- Functional relevance was assessed by correlating GamC with physical activity, autonomic nervous system function, and response to exercise intervention in centenarians.
Main Results:
- GamC demonstrated a moderate, reliable association with CA across independent cohorts.
- GamC specifically reflected current physical activity levels but showed weak correlation with autonomic nervous system function.
- GamC showed modest responsiveness to an exercise intervention in centenarians, indicating BA monitoring potential.
Conclusions:
- GamC is a simple, affordable candidate BOA for assessing current cardiovascular health-related biological age.
- GamC's ability to reflect physical activity and respond to interventions supports its use in promoting healthy aging.
- This biomarker facilitates broad clinical translation for cardiovascular health monitoring and age-related disease prevention.
Abstract:
The need to monitor the aging process as a risk factor for disease and mortality beyond chronological age (CA) has led to numerous investigations into the estimation of the biological age (BA) of individuals. However, the accuracy of BA estimation tools is often judged by their ability to approximate CA, questioning their value in capturing the variance in health status and thus correctly estimating BA. Their biological relevance is often assessed in relation to health outcomes or mortality, underexploiting their potential for real-time monitoring of BA. Furthermore, their complexity may limit their clinical translation to large populations. Here, we describe the gene expression-based age monitoring Clock (GamC), a simple biomarker of aging (BOA), and characterize its biological relevance with synchronous cardiovascular (CV) health-related functional data. GamC is calculated from the expression levels of three genes consistently dysregulated with age in blood (ABLIM1, CCR7, and LEF1). GamC shows moderate but reliable association with CA in three independent cohorts, supported by transcriptome-wide changes. It demonstrates specialized biological meaning, as it specifically describes current physical activity levels, but poorly correlates with autonomic nervous system function, both age-related factors associated with CV health. Finally, it expresses BA monitoring capacity by modestly responding to an effective exercise-based intervention in centenarians. In conclusion, GamC is proposed as a simple and affordable candidate BOA for reporting the individuals' current CV health-related BA, thus promoting its broad translation and application into measures aimed at promoting healthy aging in relation to CV health, the leading cause of death worldwide.
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