Inflammageing, a targetable pathway for preventing cardiovascular diseases

Abstract

Inflammageing, characterized by persistent chronic inflammation in older adults, has emerged as a critical factor linked to age-related diseases, such as cardiovascular diseases (CVDs), metabolic disorders, and cognitive decline, which collectively contribute to the leading causes of death globally. Elevated levels of cytokines, chemokines, and other inflammatory mediators characterize inflammageing and serve as indicators of biological age. Among the causes of inflammageing, deterioration of the immune system, mitochondrial dysfunction, dysbiosis, accumulation of DAMPs, together with genetic or epigenetic factors, contribute to inflammageing not only in CVD but also in other age-related conditions. This review examines the causes and consequences of inflammageing, particularly its implications for atherosclerosis and heart failure with preserved ejection fraction and explores potential strategies to mitigate it in the onset of CVD.

Keywords: Ageing; Atherosclerosis; HFpEF; Heart failure; Inflammation.

Figure 1

Causes of inflammageing. The presence of PAMPs due to physical rupture of intestinal barrier or persistent chronic infections activate inflammatory pathways in the IS. In addition, cells undergoing stress release DAMPs like mtDNA, formylpeptides, and ROS, and some of them become senescent with the characteristic SASP-secreting inflammatory signals. Of note, release of DAMPs, PAMPs, and SASPs contribute to inflammageing and foster the deterioration of the IS affecting to quality and quantity of immune responses and worsening inflammageing. These factors, together with intrinsic factors that contribute to the deterioration of the IS, like CHIP, myeloid skewing, high NLR, thymus involution, and antigen exposure. PAMPs, pathogen-associated molecular patterns; DAMPs, damage-associated molecular patterns; mtDNA, mitochondrial DNA; ROS, reactive oxygen species; CHIP, clonal haematopoiesis of indeterminate potential; NLR, neutrophil to lymphocyte ratio; SASP, secretory-associated senescence phenotype.

Figure 2

Molecular mechanisms of inflammageing. In the heart and the vasculature, inflammageing promotes oxidative stress and increases inflammatory mediators such as CRP and adhesion molecules that result in ECM and lipidome remodelling. Additional factors, such as epigenetic changes, including oscillations in levels of several miRNAs, has been shown to contribute to the sustained inflammation that lead to endothelial dysfunction, atherosclerosis, vascular injury, and heart failure. CVD, cardiovascular disease; HFpEF, heart failure preserved ejection fraction; CRP, C-reactive protein; ECM, extracellular matrix; PUFA, polyunsaturated fatty acids; miRNA, microRNA; IL-1, interleukin-1; IL-6, interleukin-6; TNF, tumour necrosis factor.