Spatial transcriptomic mapping of young and aged mouse hearts shows that age-related immune and fibrotic remodeling begins in the valves and aorta rather than uniformly across the myocardium. Macrophages lose homeostatic programming while fibroblast-lineage cells upregulate senescence markers including p21 and reorganize extracellular matrix, mirroring activated signatures found in human cardiac fibroblasts. Cardiac stiffening and heart failure risk therefore originate in identifiable anatomical niches, not as diffuse whole-organ decline.
Key Points
- Aging cardiac remodeling concentrates first in valves and aorta
- Macrophages lose immune homeostasis; fibroblasts upregulate senescence marker p21
- Aged mouse fibroblast programs mirror activated human cardiac fibroblasts
Longevity Analysis
Fibrosis is the structural endpoint of chronic low-grade inflammation, and localizing where that conversion begins changes how cardiac aging can be monitored and intervened upon. Valve and aortic tissue function as early convergence points between immune signaling and matrix deposition, suggesting that regional imaging and circulating fibrotic markers may detect decline long before ejection fraction or symptoms shift. Interventions that lower inflammatory load and support matrix turnover act on the same feedback loop that drives senescent fibroblast accumulation, making the window for preserving cardiac compliance considerably earlier than most clinical surveillance assumes.
Original published by Wiley Aging Cell, by Aleksandra Aljakna Khan, Amalia Sintou, Yue Zhao, Antonios Somarakis, Harshpreet Chandok, Juliana Alcoforado Diniz, Ramalakshmi Ramasamy, Gretchen T. Clark, Leon Frommer, Sikander Hayat, Brian S. White, Paul Robson, Ron Korstanje, J. Matthew Mahoney, Nadia A. Rosenthal .