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The Human Cardiac "Age-OME": Age-Specific Changes in Myocardial Molecular Expression.
Cassandra Malecki1,2, Giovanni Guglielmi1,3,4, Benjamin Hunter1
1School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Aging Cell
|September 7, 2025
Summary
Human heart ageing involves molecular changes, including reduced calcium signalling proteins and altered fuel metabolism. This research provides key insights into normal cardiac ageing and age-related heart disease development.
Area of Science:
- Cardiology
- Molecular Biology
- Gerontology
Background:
- Ageing is a primary risk factor for heart disease.
- The molecular mechanisms of human cardiac ageing remain unclear.
- Understanding cardiac ageing is crucial for preventing age-related heart conditions.
Purpose of the Study:
- To characterize the molecular landscape of normal human cardiac ageing.
- To identify age-associated molecular differences in the human heart.
- To provide a foundation for understanding age-related heart disease.
Main Methods:
- Utilized pre-mortem, cryopreserved, non-diseased human hearts from younger (≤25 years) and older (≥50 years) individuals.
- Performed multi-omics analyses: transcriptomics, proteomics, metabolomics, and lipidomics.
- Integrated omics data with biologically informed computational modelling.
Main Results:
- Observed downregulation of proteins in calcium signalling and the contractile apparatus in older hearts.
- Identified potential dysregulation in central carbon metabolism, including glycolysis and fatty acid oxidation.
- Detected an increase in long-chain fatty acids in older hearts.
Conclusions:
- This study presents the first comprehensive molecular dataset of normal human cardiac ageing.
- Findings reveal key molecular alterations in the ageing human heart.
- The data has significant implications for understanding cardiac ageing and developing strategies against age-related heart disease.
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