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cGAS/STING pathway linked to chronic inflammation and functional decline in aging

As we grow older, our bodies undergo numerous changes that can impact our overall health and make us more susceptible to diseases. One common factor in the aging process is low-grade inflammation, which contributes to age-related decline and impairment. However, the precise pathways responsible for this inflammation and their impact on natural aging have remained elusive until now.

Exciting new research led by Andrea Ablasser at EPFL has finally shed light on this mystery. The study focuses on a molecular signaling pathway called cGAS/STING, which plays a critical role in driving chronic inflammation and functional decline during aging. By blocking the STING , the researchers were able to suppress inflammatory responses in aging and tissues, leading to significant improvements in tissue function.

The cGAS/STING pathway is involved in detecting the presence of DNA in cells and triggering immune responses against viral and bacterial infections. Previous studies had already linked it to various biological processes, including , which is a key aspect of aging. Based on these connections, the research team investigated whether this pathway could underlie maladapted immune responses during aging.

Their findings were remarkable. Activating the STING protein caused specific patterns of gene activity in microglia, the immune cells that act as the brain's first line of defense. These gene activation patterns matched those seen in microglia during different neurodegenerative conditions, such as Alzheimer's disease and aging.

Digging deeper into the mechanism behind cGAS-STING activation in aging, the researchers found that DNA from malfunctioning mitochondria (the organelles responsible for energy production) accumulated in the cell cytoplasm of microglia from old mice. This accumulation suggested a possible mechanism by which the cGAS-STING pathway contributes to inflammation in the aging brain.

To validate their findings, the team performed experiments on aged mice. Blocking the STING protein led to a reduction in inflammation both in the body and the brain. Even more intriguingly, receiving STING inhibitors showed significant enhancements in spatial and associative memory, as well as improved muscle strength and endurance.

This study marks a significant step forward in understanding aging-related inflammation and offers potential strategies for slowing cognitive decline in age-associated neurodegenerative conditions. The precise insights into the neuroimmune crosstalk governing microglial-dependent neurotoxicity also hold great promise for future research on .

With this newfound knowledge, we may be better equipped to tackle age-related health challenges and potentially develop targeted therapies to improve the quality of life for older individuals.

Source: Ecole Polytechnique Federale de Lausanne

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