The Aging Heart

A new study provides a comprehensive view of how the cellular and molecular composition of the human heart changes across the lifespan.
Using single-nucleus RNA sequencing, the researchers analyzed more than 440,000 nuclei from non-failing human hearts and generated a lifespan atlas of the human myocardium. The study identified coordinated, cell type-specific changes associated with aging, including altered stress responses, inflammation, metabolic remodeling, and cardiomyocyte senescence.
A central finding was the age-associated decline in PRDM16 activity in cardiomyocytes. Functional experiments indicated that dysregulation of PRDM16 contributes to cellular senescence and metabolic dysfunction. Conversely, restoring PRDM16 activity in aged hearts improved cardiac function and partially reversed aging-associated transcriptional programs.
The researchers also developed transcriptome-based models to estimate the biological age of the heart. Application of these models revealed evidence of accelerated cardiac aging in patients with cardiomyopathies.
The study represents the beginning of a close collaboration between researchers at LMU Munich and the group of Prof. Song at Fuwai Hospital and the Chinese Academy of Medical Sciences in Beijing.

Original Publication:

Life-span-dependent transcriptional dynamics of the human heart 
Jia H, Chen X, Chang Y, Wang Y, Lindberg EL, Cui H, Feng Y, Zhang N, Zhang X, Xu M, Shan D, Sheng Y, Wei F, Hua X, Mo H, Hu Y, Shao X, Han H, Reichart D, Song J
Sci Adv. 2026 Jun 19;12(25):eaeg2614. https://doi.org/10.1126/sciadv.aeg2614