The effect of TMAO on aging-associated cardiovascular and metabolic pathways and emerging therapies

Metabolites produced by gut microbes have been linked to the pathophysiology of several disorders, including cardiovascular disease (CVD), such as atherosclerosis, hypertension, heart failure, and myocardial infarction. Trimethylamine-N-oxide (TMAO) is a primary diet-induced metabolite generated by the gut microbiota. TMAO is involved in dysregulation of bile acid and cholesterol metabolism, which promotes oxidative stress, inflammation, and endothelial dysfunction leading to vascular damages. Aging is usually associated with cardio-metabolic diseases, and the increasing evidence reveals that TMAO is linked with an increased risk of CVD in elderly. However, the exact relationship between plasma TMAO levels, the risk of CVD, and aging remains unclear. In this review, we explore the three-dimensional relationship between TMAO, aging, and CVD. Moreover, we discussed the new therapies used to reduce TMAO levels in aging and CVD.