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Novel immunoinformatics-guided activation of CISD1 with compound 4'-methoxy-3',5,7-trihydroxyflavanone for the
Abdur-Rehman Munir1, Javed Iqbal Wattoo2, Kaniz Fatima2
1Department of Biotechnology, Faculty of Science and Technology (FOST), University of Central Punjab (UCP), 1- Khayaban-E-Jinnah Road, Johar Town Lahore, Pakistan. abdulrehman47470@gmail.com.
Abstract:
Aging is a principal driver of cardiomyopathy, characterized by mitochondrial dysfunction, oxidative stress, and progressive telomere shortening in cardiomyocytes. These pathological changes impair cellular bioenergetics and regenerative capacity, accelerating cardiac deterioration. However, targeted interventions to mitigate these effects remain limited. This research investigates the therapeutic potential of CISD1 activation as a novel strategy to counteract aging-associated cardiac decline. Using advanced Immunoinformatic approaches, including molecular docking, protein structure modelling, and molecular dynamics simulations, we assess the role of CISD1 upregulation in enhancing mitochondrial bioenergetics, reducing oxidative stress, and preserving telomere integrity. Our Immunoinformatic findings reveal that CISD1 activation stabilizes mitochondrial function, mitigates oxidative damage, and slows telomere attrition, thereby sustaining cardiomyocyte function and delaying cellular senescence. Our research identifies 4'-Methoxy-3', 5,7-trihydroxy flavanone as a potential small-molecule activator of CISD1, offering a promising pharmacological approach to modulate mitochondrial dynamics in aging cardiomyocytes. By directly addressing the mechanistic link between CISD1, mitochondrial stability, and telomere preservation, this research bridges a critical gap in understanding age-related cardiomyopathy and provides a foundation for targeted therapeutic interventions. Our findings suggest that CISD1 activation could restore cellular homeostasis in aged cardiac tissues, reducing the risk of heart failure and other aging-related cardiovascular diseases. These insights advance age-related disease intervention strategies by targeting fundamental molecular pathways involved in cardiomyocyte aging.
Insights
Activating CISD1 (CD20-like protein 1) combats aging in heart cells by improving mitochondrial function and preserving telomeres. This discovery offers a new therapeutic target for age-related heart disease.
Area of Science:
- Cardiovascular Research
- Aging Biology
- Mitochondrial Medicine
Background:
- Aging is a primary cause of cardiomyopathy, marked by mitochondrial dysfunction, oxidative stress, and telomere shortening in cardiomyocytes.
- These age-related changes impair cellular energy production and regeneration, leading to cardiac deterioration.
- Current interventions for aging-related cardiac decline are limited.
Purpose of the Study:
- To investigate the therapeutic potential of activating CISD1 (CD20-like protein 1) as a strategy against aging-associated cardiac decline.
- To explore CISD1's role in enhancing mitochondrial bioenergetics, reducing oxidative stress, and preserving telomere integrity in cardiomyocytes.
- To identify potential small-molecule activators for CISD1 to modulate mitochondrial dynamics in aging hearts.
Main Methods:
- Utilized advanced immunoinformatic approaches, including molecular docking, protein structure modeling, and molecular dynamics simulations.
- Assessed the impact of CISD1 upregulation on mitochondrial function, oxidative stress markers, and telomere length.
- Screened for small molecules capable of activating CISD1.
Main Results:
- CISD1 activation was found to stabilize mitochondrial function and mitigate oxidative damage in aging cardiomyocytes.
- Activation of CISD1 significantly slowed telomere attrition, thereby delaying cellular senescence.
- Identified 4'-Methoxy-3',5,7-trihydroxyflavanone as a potential small-molecule activator of CISD1.
Conclusions:
- CISD1 activation represents a promising therapeutic strategy for counteracting age-related cardiomyopathy.
- Targeting CISD1 can restore cellular homeostasis in aged cardiac tissues, potentially reducing the risk of heart failure.
- This research provides a mechanistic link between CISD1, mitochondrial stability, and telomere preservation, advancing interventions for cardiovascular aging.
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