The STING protein is a point of convergence for a range of molecular sensors in a cell that detect damage or infection. Triggering STING activity produces an inflammatory response. Unfortunately, cell dysfunctions characteristic of aging produce issues such as the escape of fragments of mitochondrial and nuclear DNA into the cell cytosol, where they trigger sensors evolved to detect infectious agents, and thus activate STING. This contributes to the chronic inflammation of aging. For this and other reasons, researchers are considering STING inhibition as a potential form of therapy for a range of inflammatory age-related conditions. This approach has the obvious downside of also inhibiting necessary, short-term inflammatory responses, just like existing immunosuppressive therapies - but as researchers note here, STING inhibition may also produce other, less obvious harmful side effects.
The Stimulator of Interferon Genes (STING) pathway is pivotal in innate immunity, facilitating the detection of cytosolic DNA and initiating type I interferon-dependent responses. In addition to its immunological roles, STING has been increasingly associated with metabolic regulation, since research indicates that its inhibition can diminish inflammation, lipid accumulation, and tissue damage in obesity and other metabolic disorders. The findings have prompted the suggestion of STING inhibition as a viable treatment approach for metabolic illness. Nonetheless, the physiological function of STING in lipid homeostasis under normal settings remains largely unexplored, as does the impact of its absence on metabolism throughout various life stages in the absence of disease. This information deficit is crucial, particularly in light of the increasing interest in the long-term pharmacological suppression of STING.
o examine the function of STING in lipid metabolism during physiological, non-pathological conditions throughout the lifespan, we assessed wild type (WT) and STING knockout (STINGKO) mice at various ages and discovered that STING deficiency results in a consistent increase in body weight, independent of alterations in locomotor activity or food consumption. STINGKO mice exhibited markedly increased circulation levels of triglycerides and total cholesterol. Histological and morphological analysis demonstrated augmented fat accumulation in adipose and hepatic tissues, despite the lack of nutritional or genetic metabolic stress. These findings indicate a crucial function for STING in the control of lipid homeostasis across the lifespan, and caution against the prolonged use of STING inhibitors, as chronic STING suppression may lead to detrimental metabolic effects.
Link: https://doi.org/10.1...659-025-00624-3
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