Dataset Information

The Human Cardiac “Age-OME”: Age-specific changes in myocardial molecular

ABSTRACT: Ageing is one of the most significant risk factors for heart disease, however, it is still not clear how the human heart changes with age. Taking advantage of a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we performed omics analyses (transcriptomics, proteomics, metabolomics, and lipidomics), coupled with biologically-informed computational modelling in younger (≤25 years old) and older hearts (≥50 years old) to describe the molecular landscape of human cardiac ageing. In older hearts, we observed a downregulation of proteins involved in calcium signalling and contractile apparatus. Furthermore, we found a potential dysregulation of central carbon generation of fuel, glycolysis and fatty acids oxidation, along with an increase in long-chain fatty acids. This study presents and analyses the first molecular data set of normal human cardiac ageing, which has relevant implications for understanding the human cardiac ageing process and the development of age-related heart disease.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

SUBMITTER: Mark Larance

LAB HEAD: Mark Larance

PROVIDER: PXD050610 | Pride | 2025-11-17

REPOSITORIES: Pride

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			Action	DRS
	20200422_Eclipse_DH_150umCap_60min_BH_EXP1_old_1.raw	Raw
	20200422_Eclipse_DH_150umCap_60min_BH_EXP1_old_10.raw	Raw
	20200422_Eclipse_DH_150umCap_60min_BH_EXP1_old_11.raw	Raw
	20200422_Eclipse_DH_150umCap_60min_BH_EXP1_old_12.raw	Raw
	20200422_Eclipse_DH_150umCap_60min_BH_EXP1_old_13.raw	Raw

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The Human Cardiac "Age-OME": Age-Specific Changes in Myocardial Molecular Expression.

Malecki Cassandra C Guglielmi Giovanni G Hunter Benjamin B Harney Dylan D Koay Yen Chin YC Don Anthony S AS Han Oscar O Khor Jasmine J Nguyen Lisa L Pan Michael M Gawthrop Peter P Isles Nathan N Chung Joshua J Hume Robert D RD Taper Matthew M Wang XiaoSuo X Larance Mark M Spill Fabian F Rajagopal Vijay V O'Sullivan John F JF Lal Sean S

Aging cell 20250907 11

Ageing is one of the most significant risk factors for heart disease; however, it is still not clear how the human heart changes with age. Taking advantage of a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we performed omics analyses (transcriptomics, proteomics, metabolomics, and lipidomics), coupled with biologically informed computational modelling in younger (≤ 25 years old) and older hearts (≥ 50 years old) to describe the molecular landscape of human cardiac ageing. ...[more]

PMID: 40915658

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Project description:Analysis of the effects of aging on the development of dilated cardiomyopathy by characterizing both changes in ejection fraction (EF) and gene expression profile in 3 groups of male mice: Control (Cont or WT, n=11) and transgenic (Tg or KO) mice with either high EF (KO-H or Tg-H, n=7) or low EF (KO-L or Tg-L, n=6). We previously produced a line of transgenic mice (Tg) on a mixed genetic background where cardiac-specific overexpression of Cre recombinase reduced expression of the EP4 receptor gene. There were no obvious phenotypes in 10-12-week-old male Tg mice. To determine if a cardiac phenotype developed in aged mice, we assessed cardiac structure and function by echocardiography, histology and gene expression in 23-33-week-old male Tg and littermates (Cont). After echocardiography, hearts were removed to assess hypertrophy (MCSA), fibrosis (ICF) and macrophage infiltration by histological methods and for extraction of total RNA and protein. Cont mice had a normal EF of 80Â±0.6% (n=70), whereas Tg mice had a lower EF (60Â±2.7%, n=55, p<0.001) coupled with left ventricular dilatation. The distribution of EFs in the Tg mice was large, ranging from normal to below 30%. MCSA and infiltrating macrophages were not different between groups, but ICF increased by 35% in Tg mice. Cre protein levels in heart lysates did not correlate with either age or EF. In contrast to male Tg mice, female Tg mice had no cardiac dysfunction assessed by echocardiography from 12 to 28 weeks of age. To understand gene expression differences between Cont and Tg mice, whole genome gene expression profiling (Illumina BeadChips) on hearts of 30-32 week old male mice was done. Data indicated that 595 genes were overexpressed in the Tg hearts, 156 of which changed more than 2-fold, including genes involved in remodeling, inflammation, and oxidative stress. 512 genes were downregulated in the Cont hearts, 79 of which changed more than 2-fold, including genes involved with calcium handling, K+ channels, and fatty acid transport and metabolism. In conclusion, Cre overexpression and EP4 knock down in cardiac myocytes in aged male but not female Tg mice are in part associated with increased fibrosis, reduced EF and dilated cardiomyopathy; however, Cre protein itself does not seem to be responsible for the cardiomyopathy. The absence of cardiac dysfunction in female mice suggests a sexual dimorphism in the phenotype. Creation of the cardiac-myocyte specific EP4 KO mouse and littermate controls was described in JY Qian et al, Hypertension 2008: 51(pt 2):560-566. Total RNA extracted from left ventricle of control (Cont or WT, n =11) and cardiac-specific EP4 KO (Tg or KO, n=13) male mice (mean age 31 weeks).