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Updated: May 25, 2026
Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
Multi-region proteomic mapping identifies FTL1 and SERPINA3K as protective factors in cardiac aging
Jingnan Huang1,2,3, Xin Sun2,3, Huadong Liu2,3
1Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, 518020, China.
Insights
Aging cardiac function declines, increasing cardiovascular disease risk. This study identifies FTL1 and SERPINA3K as key regulators of cardiac aging, offering potential cardio-protective targets.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Proteomics
Background:
- Aging is a major risk factor for cardiovascular diseases (CVDs), linked to declining cardiac function.
- Existing cardiac proteomic atlases lack region-specific aging dynamics crucial for understanding localized mechanisms.
- Understanding cardiac aging requires detailed, spatially resolved proteomic data.
Purpose of the Study:
- To create a region-resolved proteomic atlas of cardiac aging in mice.
- To identify key proteins regulating age-associated changes in cardiac tissue.
- To elucidate the molecular mechanisms underlying cardiac aging and explore therapeutic targets.
Main Methods:
- Region-resolved quantitative proteomic profiling of murine cardiac regions at three aging stages (3, 12, 20 months).
- Integrated bioinformatics and machine learning analysis to identify age-associated protein expression changes.
- Mechanistic studies involving gene knockdown/overexpression (Ftl1, Serpina3k, Sting) and pharmacological interventions (Ferrostatin-1) in vitro and in vivo (AAV9 delivery).
Main Results:
- Quantified 6,650 proteins, revealing region-specific aging dynamics.
- Identified FTL1 and SERPINA3K as proteins with significant age-associated expression changes across cardiac regions.
- FTL1 knockdown induced cardiomyocyte ferroptosis and senescence; SERPINA3K depletion activated the cGAS-STING-PERK axis, exacerbating senescence and fibrosis.
- In vivo SERPINA3K overexpression attenuated the cGAS-STING-PERK axis and mitigated age-related cardiac fibrosis.
Conclusions:
- FTL1 and SERPINA3K are critical regulators of cardiac aging.
- This study provides a valuable region-resolved proteomic atlas of cardiac aging.
- FTL1 and SERPINA3K represent potential therapeutic targets for age-related cardiovascular disorders.
Abstract:
Aging is a well-recognized risk factor in cardiovascular diseases (CVDs), primarily due to its association with the gradual decline in cardiac function. This decline significantly influences the pathogenesis of common CVDs such as myocardial infarction and heart failure. Despite the existence of several proteomic atlases of the heart, the spatially resolved proteomic dynamics essential for understanding region-specific aging mechanisms in cardiac tissue remain incompletely characterized. In this study, we conducted a region-resolved quantitative proteomic profiling for various murine cardiac regions at three distinct stages of aging (3, 12, and 20-month-old), quantifying 6 650 proteins in the heart. Leveraging integrated bioinformatics and machine learning frameworks, we uncovered that FTL1 and SERPINA3K exhibit strong age-associated expression changes across all cardiac regions. Mechanistically, the knockdown of Ftl1 led to cardiomyocyte ferroptosis and senescence, phenotypes that were ameliorated by the ferroptosis inhibitor Ferrostatin-1. Furthermore, the depletion of Serpina3k exacerbated senescence and collagen deposition through the activation of the cGAS-STING-PERK axis, effects that can be reversed via the overexpression of Serpina3k or the knockdown of Sting. The protective effect of SERPINA3K was also demonstrated in vivo through AAV9-mediated cardiomyocyte-specific overexpression in middle-aged mice, which attenuated the cGAS-STING-PERK axis and mitigated age-related fibrosis. These results strongly demonstrated that FTL1 and SERPINA3K function as key regulators of cardiac aging. Collectively, this study provides a valuable region-resolved proteomic atlas of cardiac aging and identifies key protein regulators, thereby uncovering potential targets for cardio-protective interventions against age-related cardiovascular disorders.
