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Global and tissue-specific transcriptomic dysregulation in human aging: Pathways and predictive biomarkers
Muhammad Arif1,2,3, Andrea Lehoczki4, György Haskó5
1Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute On Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. muhammad.arif@gu.se.
Geroscience
|April 28, 2025
Summary
Aging causes tissue-wide gene expression changes, impacting inflammation and metabolism. Key biomarkers like GDF15 and EDA2R predict aging, especially in heart and liver tissues, offering targets for healthy aging.
Area of Science:
- Genomics and Molecular Biology
- Aging Research
- Systems Biology
Background:
- Aging is a universal process leading to tissue dysfunction and disease susceptibility.
- Molecular mechanisms of aging, especially tissue-specific changes, are not fully understood.
- Hallmarks of aging include mitochondrial dysfunction, inflammation, and metabolic dysregulation.
Purpose of the Study:
- To comprehensively analyze aging-associated transcriptomic changes across 40 human tissues.
- To identify shared and tissue-specific molecular signatures of aging.
- To discover novel biomarkers for aging and age-related cardiometabolic diseases.
Main Methods:
- Transcriptomic analysis of GTEx data comparing younger (<40 years) and older (>65 years) individuals.
- Differential gene expression analysis and enrichment analyses.
- Gene co-expression network analysis and machine learning for biomarker identification.
Main Results:
- Over 17,000 differentially expressed genes (DEGs) identified across tissues.
- Up-regulated DEGs linked to inflammation and apoptosis; down-regulated DEGs to mitochondrial function and metabolism.
- Identified 1,099 shared dysregulated nodes and key aging biomarkers (GDF15, EDA2R), particularly in cardiometabolic tissues.
Conclusions:
- Aging involves widespread, yet distinct, tissue-specific transcriptional shifts.
- GDF15 and EDA2R are robust aging biomarkers with relevance to cardiometabolic health.
- Findings provide insights into aging mechanisms and potential therapeutic targets for healthy aging.
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