In older individuals, chronic inflammation is often linked to inappropriate activation of innate immune pathways involving proteins like STING. Research has focused on inhibiting STING activity to address this issue, but suppressing inflammatory regulators poses challenges as these pathways are also crucial for defense and regeneration. Rather than targeting regulators of inflammation, some propose removing the triggers of inflammation – a daunting task given the complexity of these triggers.
Furthermore, blocking STING may not be a viable solution to combat age-related chronic inflammation due to its role in promoting autophagy, a process essential for cellular maintenance and longevity. STING activation leads to the creation of more lysosomes, which are crucial for autophagy. Therefore, suppressing STING could hinder autophagy and potentially hasten the aging process. These findings suggest that targeting downstream components of the inflammation pathway rather than STING itself may be a more effective approach to address age-related inflammation.
Recent studies have uncovered a new aspect of STING’s role in aging, revealing its involvement in activating genes responsible for lysosome production during cellular stress. This function of STING is vital for maintaining health and longevity, indicating that selectively targeting inflammatory components downstream of STING may be a more beneficial approach in managing age-related diseases. It is essential to reconsider the use of STING-blocking therapies to preserve its beneficial functions in promoting autophagy and lysosomal biogenesis.
In a groundbreaking discovery, researchers have identified an unexpected function of the STING protein – the promotion of lysosomal biogenesis independent of TBK1, a key factor in interferon production. Through proteomics and bioinformatics analyses, it was found that STING activates transcription factor EB (TFEB), a regulator of lysosomal biogenesis and cellular defense, in various species. This STING-mediated activation of TFEB supports lysosomal biogenesis and autophagy, processes crucial for immunity and cellular stress resistance. These findings highlight a primordial function of STING in maintaining cellular health and resilience against age-related conditions.
