Serum Galectin-3 Correlates with Frailty Risk

Galectin-3 is very broadly expressed in the body, but its connection to immune function leads to raised levels of galectin-3 in the bloodstream of patients suffering from any one of a number of inflammatory conditions that are associated with obesity, aging, or both. Consider nonalcoholic steatohepatitis (NASH), for example, where some groups are trying to inhibit galectin-3 or its interactions in order to treat the condition. It isn't clear as to where exactly galactin-3 lies in the complex web of cause and effect taking place in the liver in this condition - the only way to find out is to inhibit it and see what happens.

Frailty is an age-related condition strongly associated with chronic inflammation. In today's open access paper, researchers show that is also associated with raised galectin-3 levels. As for NASH, it is unclear as to whether galectin-3 could be targeted to reduce the burden of inflammation and dysfunction in patients with frailty, or whether it is too far downstream in the web of cause and consequence to be useful in any way other than as a marker of risk and severity.

High blood galectin-3 level associated with risk of frailty in aging

Galectin-3 (Gal-3, also known as Mac-2), a β-galactoside binding lectin, is widely expressed in human tissues, including all types of immune cells, epithelial cells, endothelial cells, stem cells, and sensory neurons. Furthermore, it is highly expressed and secreted by macrophages. As a specific regulator of many biological systems, Gal-3 is highly promiscuous and localized within the tissue micro-environment, including extracellular, cytoplasmic, and nuclear. The different locations of Gal-3 contribute to its various functions.

Secreted Gal-3 is pivotal in numerous biological activities including cell growth, differentiation, transformation, apoptosis, angiogenesis, inflammation, fibrosis, and host defense. Also, it is able to cross-link surface glycoproteins and stimulate important pathways involved in the innate immune response such as the oxidative burst in neutrophils, alternative macrophage (M2) activation, and mast-cell degranulation.

Previous studies have reported that elevated blood Gal-3 level in humans was related to exacerbating disease in inflammatory, metabolic, and malignant diseases. Elevated serum Gal-3 levels have been detected in almost all types of cardiovascular disease. However, little is known about the function of Gal-3 in frailty. Moreover, the physiological relevance of whole-blood Gal-3 to predict aging-associated conditions clearly needs further investigation. Thus, monitoring circulating Gal-3 levels in humans could help us understand the mechanism of aging and frailty, leading the way to finding potential treatments.

A chronic state of low-grade inflammation, accompanied by a dysregulation of the inflammatory cytokine network, has been indicated as a major driver of age-associated conditions. A previous study also proposed that the association of inflammatory factors such as C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels with frailty may reflect the phenotype of inflammaging. Hence, we speculated that the association of frailty and Gal-3 might also be mediated by inflammatory cytokine networks.

Nevertheless, up to now, there is very limited evidence on the frailty status in human Gal-3-related studies. In this study, we aimed to address the change of Gal-3 levels in human whole blood with frailty. We performed serum biochemical and peripheral blood mononuclear cells (PBMC) microarray analyses in humans to determine the secretory phenotype characteristics of frailty. Furthermore, we used the frail mouse model to study the significantly altered behavioral phenotype and associated secreted Gal-3 levels in blood samples to reveal the Gal-3-dependent inflammatory dysregulation of frailty.