ArticleAmerican journal of physiology. Heart and circulatory physiology2022
Proteogenomics reveals sex-biased aging genes and coordinated splicing in cardiac aging.
Article in American journal of physiology. Heart and circulatory physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Circulating extracellular vesicles in plasma carry accessible molecular signatures of aging in mice.bioRxiv : the preprint server for biology · 2026Article
- RNA imbalance as a hallmark of cellular ageing.Nature cell biology · 2026Review
- Prenatal glucocorticoid exposure programs long-term left ventricular metabolism, function, and remodeling in baboons.American journal of physiology. Heart and circulatory physiology · 2026Article
- Cell-type-specific alternative splicing in the brain and kidney of a Setbp1S858R Schinzel-Giedion syndrome mouse.Disease models & mechanisms · 2026Article
- SALVE: prediction of interorgan communication with transcriptome latent space representation.American journal of physiology. Heart and circulatory physiology · 2025Article
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- Transcript diversity in aging: cryptic transcription and splicing.Medical review (2021) · 2025Review
- Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles.Aging cell · 2025Article
- Review
- Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks.Open biology · 2024Review
- Repurposing Drugs for Senotherapeutic Effect: Potential Senomorphic Effects of Female Synthetic Hormones.Cells · 2024Article
- Unlocking the dark matter: noncoding RNAs and RNA modifications in cardiac aging.American journal of physiology. Heart and circulatory physiology · 2024Review
- Sex as a biological variable for cardiovascular physiology.American journal of physiology. Heart and circulatory physiology · 2024Review
- Cardiovascular aging: spotlight on mitochondria.American journal of physiology. Heart and circulatory physiology · 2024Review
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Review
- Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches.American journal of physiology. Heart and circulatory physiology · 2023Review
- Seeking clarity on sex differences in cardiovascular complications of Down syndrome.American journal of physiology. Heart and circulatory physiology · 2023Article
- Sex chromosome mechanisms in cardiac development and disease.Nature cardiovascular research · 2023Article
- Senescence in human AC16 cardiac cells is associated with thymidine kinase induction and histone loss.microPublication biology · 2023Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
The risks of heart diseases are significantly modulated by age and sex, but how these factors influence baseline cardiac gene expression remains incompletely understood. Here, we used RNA sequencing and mass spectrometry to compare gene expression in female and male young adult (4 mo) and early aging (20 mo) mouse hearts, identifying thousands of age- and sex-dependent gene expression signatures. Sexually dimorphic cardiac genes are broadly distributed, functioning in mitochondrial metabolism, translation, and other processes. In parallel, we found over 800 genes with differential aging response between male and female, including genes in cAMP and PKA signaling. Analysis of the sex-adjusted aging cardiac transcriptome revealed a widespread remodeling of exon usage patterns that is largely independent from differential gene expression, concomitant with upstream changes in RNA-binding protein and splice factor transcripts. To evaluate the impact of the splicing events on cardiac proteoform composition, we applied an RNA-guided proteomics computational pipeline to analyze the mass spectrometry data and detected hundreds of putative splice variant proteins that have the potential to rewire the cardiac proteome. Taken together, the results here suggest that cardiac aging is associated with 1) widespread sex-biased aging genes and 2) a rewiring of RNA splicing programs, including sex- and age-dependent changes in exon usages and splice patterns that have the potential to influence cardiac protein structure and function. These changes contribute to the emerging evidence for considerable sexual dimorphism in the cardiac aging process that should be considered in the search for disease mechanisms.
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