Ceereena Ubaida‐Mohien

Higher Frontal Cortex Angiotensin Type 2 Receptor‐Interacting Protein ( ATIP ) Levels Are Associated With a Lower Amyloid‐Beta Burden in Postmortem Brains of Older Adults With Alzheimer's Disease

Çağlar Coşarderelioğlu, Simion Kreimer, Alma I. Plaza‐Rodriguez, Pablo A. Iglesias et autres

ABSTRACT Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by amyloid‐β (Aβ) and tau accumulation. Dysregulation of the brain renin‐angiotensin system, particularly hyperactivation of the angiotensin II type‐1 receptor, contributes to AD pathogenesis. In contrast, activation of the angiotensin II type‐2 …

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Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy

Olaya Santiago‐Fernández, Luisa Coletto, Inmaculada Tasset, Susmita Kaushik et autres

Chaperone-mediated autophagy (CMA) contributes to proteostasis maintenance by selectively degrading a subset of proteins in lysosomes. CMA declines with age in most tissues, including skeletal muscle. However, the role of CMA in skeletal muscle and the consequences of its decline remain poorly …

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Electron Microscopy and Multi‐Omics Reveal Mitochondrial Dysfunction and Structural Remodeling in the Hearts of Elderly Mice

Manuela Giovanna Basilicata, Marco Malavolta, Serena Marcozzi, Eduardo Sommella et autres

Aging is a key driver of cardiac dysfunction, promoting structural remodeling, metabolic alterations, and loss of cellular resilience. In aged hearts, extracellular matrix remodeling and collagen accumulation reduce ventricular compliance, impairing both diastolic function and stress adaptability. Cardiomyocytes exhibit diminished regenerative capacity …

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Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians

Ceereena Ubaida‐Mohien, Ruin Moaddel, Sally Spendiff, Norah J. MacMillan et autres

Physical function declines with aging, yet there is considerable heterogeneity, with some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical function with aging, we performed proteomics, targeted metabolomics, and targeted kynurenine-focused metabolomic …

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Healthy Aging Metabolomic and Proteomic Signatures Across Multiple Physiological Compartments

Ruin Moaddel, Julián Candia, Ceereena Ubaida‐Mohien, Toshiko Tanaka et autres

The study of biomarkers in biofluids and tissues expanded our understanding of the biological processes that drive physiological and functional manifestations of aging. However, most of these studies were limited to examining one biological compartment, an approach that fails to recognize that …

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Skeletal Muscle mRNA Splicing Variants Association With Four Different Fitness and Energetic Measures in the GESTALT Study

Stefano Donegà, Nirad Banskota, Esha Gupta, Marta González‐Freire et autres

ABSTRACT Background Physical activity is essential for maintaining muscle mitochondrial function and aerobic capacity. The molecular mechanisms underlying such protective effects are incompletely understood, in part because it is difficult to separate the effects of disease status and physical activity. We explored …

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MULTIPLE MEASURES OF FITNESS ASSOCIATION WITH MUSCLE MRNA SPLICING VARIANTS IN THE GESTALT STUDY

Stefano Donegà, Nirad Banskota, Marta González‐Freire, Ann Zenobia-Moore et autres

Abstract Regular physical activity has been associated with higher skeletal muscle mass and strength as well as better mitochondrial function. Previous studies in master octogenarian athletes found a higher content of mitochondrial- and reduced spliceosome proteins compared to non-athlete age/sex-matched controls. These …

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Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors

Çağlar Coşarderelioğlu, Simion Kreimer, Alma I. Plaza‐Rodriguez, Pablo A. Iglesias et autres

Background The renin-angiotensin system plays a crucial role in human physiology, and its main hormone, angiotensin, activates 2 G-protein-coupled receptors, the angiotensin type-1 and type-2 receptors, in almost every organ. However, controversy exists about the location, distribution, and expression levels of these …

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Epigenetic signature of human immune aging in the GESTALT study

Roshni Roy, Pei‐Lun Kuo, Julián Candia, Dimitra Sarantopoulou et autres

Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood-borne immune cell types …

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Age-related changes in human skeletal muscle microstructure and architecture assessed by DT-MRI and their association with muscle strength

Donnie Cameron, David A. Reiter, Fatemeh Adelnia, Ceereena Ubaida‐Mohien et autres

Here we apply diffusion-tensor-(DT)-MRI to study muscle microstructural and architectural changes with healthy ageing in 94 participants (median age=56, range=22-89yrs). Fractional anisotropy (FA) and mean diffusivity (MD), were calculated for 12 thigh muscles, as were pennation angle, fascicle length, fibre curvature, and …

Transcriptomes of human primary skin fibroblasts of healthy individuals reveal age‐associated mRNAs and long noncoding RNAs

Dimitrios Tsitsipatis, Jennifer L. Martindale, Krystyna Mazan‐Mamczarz, Allison B. Herman et autres

Changes in the transcriptomes of human tissues with advancing age are poorly cataloged. Here, we sought to identify the coding and long noncoding RNAs present in cultured primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22-89 years …

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Author response: Epigenetic signature of human immune aging in the GESTALT study

Roshni Roy, Pei‐Lun Kuo, Julián Candia, Dimitra Sarantopoulou et autres

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