In a mouse model expressing progerin exclusively in cardiomyocytes, loss of the m6A methyltransferases METTL3 and METTL14 was sufficient to produce myocardial fibrosis, hypertrophy, and progressive functional decline. Reduced m6A writer activity suppressed the calcium-handling transcript Casq2 while raising senescence and type I interferon transcripts, and cardiomyocyte-targeted restoration of METTL14 partially reversed the pathological remodeling.
Key Points
- Progerin in cardiomyocytes alone reproduces progeria cardiac fibrosis and hypertrophy
- METTL3/14 loss lowers Casq2, raises senescence and interferon transcripts
- METTL14 restoration partially reverses remodeling and functional decline
Longevity Analysis
Cardiac aging here is driven not by structural damage accumulating passively but by a breakdown in how heart muscle cells read and stabilize their own RNA messages — the calcium-handling machinery that governs each contraction is silenced while inflammatory signaling is amplified. Restoring a single epitranscriptomic writer recovered part of that lost function, indicating that aged myocardium retains regenerative and contractile capacity when the interpretive layer above the genome is corrected. For cardiovascular aging more broadly, it positions inflammatory activation and calcium mishandling as downstream readouts of a shared upstream control point rather than independent targets.
Original published by Wiley Aging Cell, by Shixiao Wang, Jie Zhang, Ying Ao, Dan Rao, Cong Yu, Chenzhong Xu, Ming Wang, Mingying Li, Xin Huang, Jianfei Zhang, Rui Mei, Zhen Zhang, Jie Sun, Juanli Duan, Ying Sun, Zimei Wang, Wen Su, Baohua Liu .