Rethinking cardiovascular ageing

This spotlight issue aims to give an update on the recent insights on the physiological and accelerated forms of cardiovascular (CV) ageing involving a complex interaction between immuno-inflammation, oxidative stress, cellular senescence, and epigenetics. Ministrini et al.1 review molecular biomarkers of CV and cerebrovascular ageing and new drugs or lifestyle interventions either for prevention and for treatment. Each of the major mechanisms is extended and supported by recent findings. For example, the role of the TERT component of the telomerase complex in genomic instability is highlighted by its association with clonal hematopoiesis; the role of lncRNA H19 is associated with the risk of death and lacunar stroke, and dysfunction in energy metabolism via growth factors and their receptors, deposition of misfolded transthyretin in cardiac amyloidosis. The accumulation of senescence cells resulted in the emergence of new senolytic drugs. Likewise, inhibitors of metalloproteinases, cell–cell and cell–matrix communications, preponderance of pro-inflammatory pathways over immune-inflammation resolution signalling, and gut microbial-metabolite TMAO (trimethyl-lamine N-oxide) are considered to contribute to ageing. Accelerated epigenetic age mediated by immune-inflammation is highlighted by considerable research into new molecules; some of which, as sirtuin activators, SGLT2 inhibitors, or GLP-1 agonists, are already undergoing clinical trials.