Ageing, metabolism and cardiovascular disease

Abstract

Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart.

Figure 1. Projections of crude cardiovascular disease prevalence (%), 2010 –2030 in the United States

Modified.

Figure 2. Structural changes of the aged vasculature

ECM, extracellular matrix; VSMCs, vascular smooth muscle cells.

Figure 3. Schematic representation of the molecular pathways linking ageing, metabolism and cardiovascular disease

ROS, reactive oxygen species; eNOS, endothelial nitric oxide synthase; NF‐kB, nuclear factor‐kappa B; AMPK, AMP‐activated protein kinase; FOXOs, Forkhead box O; IGF‐1, insulin growth factor‐1; mTOR, mammalian target of rapamycin.