Heart structure and function change with age, and the notion that the heart may age faster for some individuals than for others has driven interest in estimating cardiac age acceleration. However, current approaches have limited feature richness (heart measurements; radiomics) or capture extraneous data and therefore lack cardiac specificity (deep learning [DL] on unmasked chest MRI). These technical limitations have been a barrier to efforts to understand genetic contributions to age acceleration. We hypothesized that a video-based DL model provided with heart-masked MRI data would capture a rich yet cardiac-specific representation of cardiac aging. In 61,691 UK Biobank participants, we excluded noncardiac pixels from cardiac MRI and trained a video-based DL model to predict age from one cardiac cycle in the 4-chamber view. We then computed cardiac age acceleration as the bias-corrected prediction of heart age minus the calendar age. Predicted heart age explained 71.1% of variance in calendar age, with a mean absolute error of 3.3 years. Cardiac age acceleration was linked to unfavorable cardiac geometry and systolic and diastolic dysfunction. We also observed links between cardiac age acceleration and diet, decreased physical activity, increased alcohol and tobacco use, and altered levels of 239 serum proteins, as well as adverse brain MRI characteristics. We found cardiac age acceleration to be heritable (h2g 26.6%); a genome-wide association study identified 8 loci related to linked to cardiomyopathy (near and ) and an additional 16 loci (near ). Of the discovered loci, 21 were not previously associated with cardiac age acceleration. Mendelian randomization revealed that lower genetically mediated levels of 6 circulating proteins (MSRA most strongly), as well as greater levels of 5 proteins (LXN most strongly) were associated with cardiac age acceleration, as were greater blood pressure and Lp(a). A polygenic score for cardiac age acceleration predicted earlier onset of arrhythmia, heart failure, myocardial infarction, and mortality. These findings provide a thematic understanding of cardiac age acceleration and suggest that heart- and vascular-specific factors are key to cardiac age acceleration, predominating over a more global aging program.
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http://dx.doi.org/10.1101/2024.08.02.24310874 | DOI Listing |
Aging Cell
December 2024
Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, China Medical University, Shenyang, China.
Little evidence exists regarding the associations between clinical parameter-based biological aging and the incidence and outcome of chronic kidney disease (CKD). Thus, we aimed to assess the associations between biological aging, genetic risk, and the risk of CKD, as well as investigate the impact of accelerated biological aging on life expectancy. 281,363 participants free of kidney diseases from the UK Biobank were included in this prospective study.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Impact Accelerator Unit, Keele University, Keele, Staffordshire, UK.
Objective: Africa contributes significantly to the increasing global prevalence (>37 %), unmet need and treatment burden for people with osteoarthritis. Despite this, little research has examined the expressed needs of patients with osteoarthritis (OA) and joint pain in West-Africa. This study aimed to explore lived experiences, expressed needs and current care gaps for people living with osteoarthritis in low-health resource contexts using Nigeria as a case study.
View Article and Find Full Text PDFARYA Atheroscler
January 2024
Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
Background: Type 1 diabetes (T1D) carries a significant risk of atherosclerosis as the main driver for cardiovascular events. Atherosclerosis is initiated by the activation of the endothelium by various risk factors through the inflammation process. The anti-inflammatory cytokine TGF-β1 may inhibit the development of atherosclerosis.
View Article and Find Full Text PDFFront Public Health
December 2024
Department of Gastroenterology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian, China.
Objective: This study investigates the association between phenotypic age acceleration (PAA) and all-cause and cause-specific mortality in obese individuals.
Methods: Data were drawn from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018, including 9,925 obese adults (BMI ≥ 30 kg/m). PAA, defined as phenotypic age exceeding chronological age, was assessed using clinical biomarkers.
Ophthalmology
December 2024
John P. Hussman Institute for Human Genomics, University of Miami, FL; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, FL.
Purpose: To investigate the association between epigenetic age acceleration and glaucoma progression.
Design: Retrospective cohort study.
Participants: 100 primary open-angle glaucoma (POAG) patients with fast progression and 100 POAG patients with slow progression.
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