Identification of candidate long non-coding RNAs and mRNAs associated with heart aging in mice

BACKGROUND: Understanding the molecular mechanisms underlying cardiac aging may uncover novel therapeutic targets for age-related cardiovascular disease. Long non-coding RNAs (lncRNA), which regulate cell differentiation and disease progression, are emerging as promising diagnostic biomarkers and therapeutic candidates. However, their expression profiles and functional roles in the aging heart remain poorly characterized. METHODS: Male C57BL/6 wild type mice aged 20 months (aged group) and 3 months (young group) underwent transthoracic echocardiography to evaluate cardiac function. Myocardial aging phenotypes were assessed using hematoxylin-eosin, Masson's trichrome, terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), and senescence-associated β-galactosidase staining. Transcriptomic profiling was performed using a lncRNA-focused microarray platform to identify differentially expressed lncRNAs and mRNAs in heart tissues. RESULTS: Aged mice showed increased heart weight/body weight and heart weight/tibia length ratios. Both interventricular septum in systole and left ventricular posterior wall in diastole were elevated, while ejection fraction and fractional shortening remained unchanged. The Tei index was significantly higher, suggesting impaired myocardial performance. Histological staining revealed enlarged cardiomyocytes, increased myocardial fibrosis, enhanced apoptosis, and greater senescence-associated β-galactosidase activity. Microarray analysis identified distinct age-related expression patterns of lncRNAs and mRNAs in the heart. CONCLUSIONS: Cardiac aging is characterized by structural and functional remodeling, accompanied by transcriptional reprogramming involving both lncRNAs and mRNAs. These changes offer insights into potential molecular mechanisms and provide candidate regulatory targets for diagnosis and intervention in age-related heart disease.