Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis

Sarcopenia, obesity and their coexistence, obese sarcopenia (OBSP) as well as atherosclerosis-related cardio-vascular diseases (ACVDs), including chronic heart failure (CHF), are among the greatest public health concerns in the ageing population. A clear age-dependent increased prevalence of sarcopenia and OBSP has been registered in CHF patients, suggesting mechanistic relationships. Development of OBSP could be mediated by a crosstalk between the visceral and subcutaneous adipose tissue (AT) and the skeletal muscle under conditions of low-grade local and systemic inflammation, inflammaging. The present review summarizes the emerging data supporting the idea that inflammaging may serve as a mutual mechanism governing the development of sarcopenia, OBSP and ACVDs. In support of this hypothesis, various immune cells release pro-inflammatory mediators in the skeletal muscle and myocardium. Subsequently, the endothelial structure is disrupted, and cellular processes, such as mitochondrial activity, mitophagy, and autophagy are impaired. Inflamed myocytes lose their contractile properties, which is characteristic of sarcopenia and CHF. Inflammation may increase the risk of ACVD events in a hyperlipidemia-independent manner. Significant reduction of ACVD event rates, without the lowering of plasma lipids, following a specific targeting of key pro-inflammatory cytokines confirms a key role of inflammation in ACVD pathogenesis. Gut dysbiosis, an imbalanced gut microbial community, is known to be deeply involved in the pathogenesis of age-associated sarcopenia and ACVDs by inducing and supporting inflammaging. Dysbiosis induces the production of trimethylamine-N-oxide (TMAO), which is implicated in atherosclerosis, thrombosis, metabolic syndrome, hypertension and poor CHF prognosis. In OBSP, AT dysfunction and inflammation induce, in concert with dysbiosis, lipotoxicity and other pathophysiological processes, thus exacerbating sarcopenia and CHF. Administration of specialized, inflammation pro-resolving mediators has been shown to ameliorate the inflammatory manifestations. Considering all these findings, we hypothesize that sarcopenia, OBSP, CHF and dysbiosis are inflammaging-oriented disorders, whereby inflammaging is common and most probably the causative mechanism driving their pathogenesis.