Inflammaging and Senescence-Driven Extracellular Matrix Remodeling in Age-Associated Cardiovascular Disease

Area of Science:

• Cardiovascular Science
• Aging Biology
• Molecular Medicine

Background:

• Cardiovascular aging is a major contributor to global cardiovascular disease burden, especially in older adults.
• Age-related cardiovascular remodeling involves chronic inflammation (inflammaging), oxidative stress, cellular senescence, and extracellular matrix changes.
• These factors impair endothelial function, promote fibrosis, and compromise cardiac and vascular integrity.

Purpose of the Study:

• To review the molecular and cellular mechanisms of cardiovascular remodeling in aging.
• To explore the role of key molecular pathways and aging hallmarks in cardiovascular disease.
• To discuss emerging molecular therapies for age-related cardiovascular conditions.

Main Methods:

• Review of molecular and cellular mechanisms.
• Analysis of key molecular pathways (e.g., RAAS, NF-κB, NLRP3 inflammasome, IL-6, TGF-β).
• Examination of aging hallmarks like inflammaging, oxidative stress, senescence, and ECM remodeling.

Main Results:

• Chronic inflammation, oxidative stress, and cellular senescence drive maladaptive cardiovascular remodeling.
• Key molecular pathways contribute to vascular cell transdifferentiation, immune dysregulation, and tissue stiffening.
• Senescence-associated secretory phenotype and mitochondrial dysfunction perpetuate detrimental cascades.

Conclusions:

• Understanding the molecular basis of cardiovascular aging and remodeling is crucial.
• Emerging therapies like senolytics, Nrf2 activators, and ECM modulators offer potential to reverse or halt maladaptive remodeling.
• Targeting aging mechanisms provides new avenues for improving cardiovascular outcomes in older adults.