Microvascular ageing links metabolic disease to age-related disorders: the role of oxidative stress and inflammation in promoting microvascular dysfunction.

ABSTRACT Longer life span and increased prevalence of chronic, non-communicable, inflammatory diseases fuel cardiovascular mortality. The microcirculation is central in the crosstalk between ageing, inflammation, cardiovascular and metabolic diseases. Microvascular dysfunction, characterized by alteration in the microvascular endothelial function and wall structure, is described in an increasing number of chronic, age-associated diseases, suggesting it might be a marker of ageing superior to chronological age. The aim of this review is to thoroughly explore the connections between microvascular dysfunction, ageing and metabolic disorders by detailing the major role played by inflammation and oxidative stress in their evolution. Older age, hypertension, nutrient abundance and hyperglycaemia concur in the induction of a persistent low-grade inflammatory response, defined as meta-inflammation or inflammageing. This increases the local generation of reactive oxygen species that further impairs endothelial function and amplifies the local inflammatory response. Mitochondrial dysfunction is a hallmark of many age-related diseases. The alterations of mitochondrial function promote irreversible modification in microvascular structure. The interest in the hypothesis of chronic inflammation at the centre of the ageing process lies in its therapeutic implications. Inhibition of specific inflammatory pathways has been shown to lower the risk of many age-related diseases, including cardiovascular disease. However, the whole architecture of the inflammatory response underpinning the ageing process and its impact on the burden of age-related diseases remain to be fully elucidated. Additional studies are needed to unravel the connection between these biological pathways and to address their therapeutic power in terms of cardiovascular prevention.