Editorial: Inflammaging and immunosenescence: role in aging-associated cardiovascular diseases
Year: 2025
Type: editorial
Abstract: Aging is associated with chronic low-grade inflammation, known as "inflammaging", and a decline in function of immune system, "immunosenescence", both of which drive age-related disruption of molecular and cellular homeostasis leading to a range of diseases. Increasingly, research points to immune system dysfunction and chronic inflammation as key drivers of vascular, heart, kidney, and liver injury, or even post-viral immune response dysregulation leading to cardiovascular disease (CVD) pathogenesis. Although inflammaging and immunosenescence as central modulators of agingassociated cardiovascular disease progression and complications has been proven, precise characterization of this health condition in elderly people is still challenging, and more studies in this area are needed to clarify biological pathways involving inflammaging and immunosenescence in different organs. This editorial summarizes new findings from recent studies including small vasculature, pulmonary artery, dietary anti-oxidant, and long COVID, which imply the pivotal role of inflammaging and immunosenescence in aging-associated CVD.Müller et al., (1) describe in a review paper the process of interaction between immunosenescence and inflammaging driving cardiovascular disease through activating NF-κB and NLRP3 inflammasome pathways, triggering release of IL-1β, IL-6 and IL-18 pro-inflammatory cytokines and production of oxidative stress, promoting vascular damage and atherosclerosis. This inflammatory condition is further exacerbated by immune cell (macrophages, T cells) dysfunction and release of mitochondrial DNA fragments (Damage-associated molecular patterns [DAMPs]) and Reactive Oxygen Species (ROS). Authors explained the interaction of inflammation and decline of immune function in the elderly creating a vicious cycle process starting by immunosenescence inducing persistence of inflammation which in turn accelerates immune dysfunction leading to increased risk of CVD. Furthermore, these effects disturbed cellular damage repair and anti-oxidant processes. Authors highlighted emerging research describing long-term cardiovascular complications (heart failure, stroke, arrhythmias) associated with COVID-19 infection in elderly people, characterized by fibrosis and vascular damage, suggesting exaggeration of pathologic condition due to immunosenescence and inflammaging. They conclude their review by highlighting the urgent need for research to develop strategies that alleviate vascular dysfunction for vulnerable elderly populations and to promote healthier aging.Small vasculature endothelial dysfunction triggers vascular injuries, a precursor of CVDs, which is a major cause of mortality and comorbidity in elderly people. A review by Kasal et al., (2) describes the interaction between microvascular endothelial dysfunction and inflammation in vascular senescence and disease. The review describes the microvascular dysfunction as a precursor emerging early in aging, and a marker predicting cardiovascular risks associated with increase in oxidative stress and decrease in nitric oxide (NO), driving endothelial cell senescence. Chronic low-grade inflammation ("inflammaging") dysregulates homeostasis leading to age-related CVD disease. The review highlighted the role of oxidative stress during the mitochondrial respiration process and the production of reactive oxygen species (ROS), driving immune cell dysfunction and epigenetic changes. More specifically, they describe the process of chronic inflammation, uncoupling endothelial nitric oxide synthase (eNOS) and ROS generation promoted by NADPH oxidase (Nox), leading to vascular damage and activation of cell senescence and immune signaling pathways (NF-κB/NLRP3), triggering vascular inflammation through pro-inflammatory cytokine release. Activation of NLRP3, NF-κB inflammatory pathways, oxidative stress and endothelial dysfunction are promoted by trimethylamine N-oxide (TMAO) during dysbiosis. However, short-chain fatty acids (SCFAs) reduce inflammation and arterial stiffness, and their decrease is usually correlated with vascular aging. Kasal et al., emphasize this in potential strategies targeting mitigation of end-organ damage and age-related vascular injury.Vascular remodeling, stiffness and dysfunction is a hallmark of the pulmonary artery (PA) in elderly people, leading to vascular damage and associated diseases including pulmonary arterial hypertension (PAH). To measure PA stiffness, PA global longitudinal strain (GLS) and non-contrast cardiovascular magnetic resonance (CMR) are the least invasive methods compared to invasive echocardiograms or hemodynamics used mainly for disease cohorts. To potentially enable early detection and targeted therapies for pulmonary vascular diseases and to identify metabolic pathways underlying PA stiffness, Zhang et al., (3) investigated PA stiffness using an approach linking serum metabolomics with PA GLS. Vascular damage is associated with metabolic disorders identified by circulating metabolites such as lipids, oxidative stress markers or amino acids. These molecular fingerprints are used as metabolic predictors for vascular injuries. In a prospective study using a cohort of 170 old people, Zhang et al., (3) find that CMR, PA GLS were associated with cardiovascular risks and aging. Furthermore, they suggested the implication of collagen synthesis, fatty acid oxidation and gluconeogenesis as metabolic pathways involved in PA stiffness, and that PA GLS may serve as a new tool to identify early metabolic dysregulation related to pulmonary dysfunction in elderly asymptomatic people.Metabolic dysfunction in elderly peoples is usually associated with imbalances in oxidative stress pathways, leading to complication of both systemic and cardiovascular injuries. Dietary antioxidant intake, evaluated by The Composite Dietary Antioxidant Index (CDAI), has shown potential benefic effect in inflammation and oxidative stress associated with diabetes and obesity. However, there is no clear evidence on the effect in prevalence of CVD in elderly. Run Wang et al. (4) investigated the association of CDAI with cardiovascular disease in adults. They analyzed data's of 25,997 adult from NHANES (2011-2020). They revealed a negative association between CDAI and CVD prevalence. In their study, they highlighted a gender specific protective effects suggesting mitigation of CVD risks particularly in women. The study is original, however, and to confirm their finding, prospective studies are helpful to confirm causality and to deeply unravel the signaling pathways associated.
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4410380169