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SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Cellular Senescence, Inflammaging and Cardiovascular Disease
Lukas Zanders1,2,3, Denada Arifaj1,4, Julian U G Wagner1,2,4
1Institute of Cardiovascular Regeneration, Frankfurt, Germany.
Insights
Cardiovascular aging drives heart disease risk. Targeting aging processes, like cellular senescence and inflammaging, offers new strategies for cardiovascular health and disease prevention.
Area of Science:
- Cardiovascular Science
- Gerontology
- Immunology
Background:
- Aging is the primary unmodifiable risk factor for cardiovascular disease (CVD).
- Cardiovascular aging involves cellular senescence and the senescence-associated secretory phenotype (SASP), contributing to inflammaging.
- Understanding these aging mechanisms is crucial for developing interventions.
Purpose of the Study:
- To review current knowledge on cardiovascular aging.
- To highlight the roles of cellular senescence, SASP, and inflammaging in cardiovascular dysfunction.
- To explore therapeutic strategies targeting aging pathways for cardiovascular health.
Main Methods:
- Literature review of aging effects on the cardiovascular system.
- Analysis of cellular senescence, SASP, and inflammaging.
- Examination of biomarkers, animal models, and systems biology approaches.
- Review of therapeutic strategies including senolytics and SASP modulators.
Main Results:
- Cellular senescence and SASP contribute to chronic inflammation and tissue remodeling (inflammaging).
- Macrophages play a key role in clearing senescent cells.
- Existing drugs like metformin show potential anti-aging effects relevant to cardiovascular protection.
- Despite progress, direct therapies for senescence and inflammaging in CVD are needed.
Conclusions:
- Targeting cardiovascular aging, including senescence and inflammaging, is a promising strategy for long-term cardiovascular health.
- Senolytics, SASP modulation, and anti-inflammatory/metabolic interventions show therapeutic potential.
- Further research is needed to develop and validate therapies that directly address aging pathways to reduce CVD burden.
Abstract:
Aging is the most important yet unmodifiable risk factor for cardiovascular disease (CVD). As a result, targeting cardiovascular aging has emerged as a promising strategy to promote long-term cardiovascular health. This review summarizes current knowledge on the effects of aging within the cardiovascular system as well as systemic processes that modulate them. We highlight the roles of cellular senescence and the senescence-associated secretory phenotype (SASP), emphasizing their heterogeneous contributions to chronic low-grade inflammation and tissue remodeling-collectively termed inflammaging. Advances in biomarkers, animal models, and systems biology approaches have deepened our understanding of the interplay between senescence, inflammaging, and cardiovascular dysfunction, including the pivotal role of macrophages in senescent cell clearance. Therapeutic strategies are diverse, ranging from senolytic approaches designed to selectively eliminate senescent cells, to SASP modulation, and interventions targeting chronic inflammation and metabolic dysregulation. Of particular interest, drugs already in clinical use-such as metformin and other anti-diabetic agents-show beneficial effects on aging-related pathways, suggesting that their cardiovascular protection may in part reflect anti-aging properties. Despite these advances, therapies directly targeting senescence and inflammaging to reduce the global burden of CVD remain an urgent unmet need.
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