Decoding noncoding RNAs in regulating cardiovascular aging and age-related conditions: the emerging landscape

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, accounting for approximately 17.9 million deaths each year (31% of all global deaths). Cardiovascular aging (CVA) not only contributes to the aging of other organ systems, leading to systemic aging in individuals, but also induces CVDs that impose serious health challenges and exacerbate CVA. Notably, non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs have emerged as key players in CVA and associated CVDs (AR-CVDs) by acting as pro-aging, anti-aging, or dual-regulating ncRNAs. They influence both vascular aging and cardiac aging processes through modulating pro-aging or anti-aging substrates and triggers, leading to cellular senescence and CVA-related phenotypes and associated pathological processes, including hypertension, atherosclerosis, coronary heart disease, cardiac hypertrophy, heart failure, and arrhythmias. This review aims to provide an overview of the current understanding of ncRNAs in CVA and AR-CVDs, focusing on the published studies that utilize in vitro and in vivo models of aging and aging-related cardiovascular pathophysiological processes. It does not aim to exhaustively cover all ncRNA studies unrelated to aging but to present a more holistic and integrated perspective on the diverse roles of miRNAs, lncRNAs, and circRNAs in the context of CVA and AR-CVDs. In doing so, we will explore both shared and unique aspects of ncRNAs from various angles, shedding light on their regulatory roles in CVA and AR-CVDs, which may offer insights into the current state and future directions of the field. By integrating recent findings and ongoing research, this review seeks to elucidate the intricate network of ncRNAs in CVA and AR-CVDs, paving the way for novel approaches to combat one of the most pressing health challenges of our time.