Tryptophan Metabolism Regulates Immunosenescence And Inflammaging: The Macrophage Immunometabolic Axis And Therapeutic Targets
As we age, our immune system can become less effective, a process called immunosenescence, and we often experience a persistent, low-grade inflammation known as inflammaging. Recent research sheds light on a key player in these age-related changes: the way our bodies process an essential amino acid called tryptophan. This process, particularly within immune cells called macrophages, appears to be central to how our immune system ages.
The study proposes a model where an imbalance in gut bacteria, common in older individuals, leads to a reduction in beneficial compounds produced by these microbes. This disruption affects how macrophages in the gut respond, weakening the gut barrier and allowing harmful substances to enter the bloodstream.
Once in the body, these substances trigger an overactivation of a specific pathway that processes tryptophan, leading to macrophages becoming more pro-inflammatory. This creates a self-sustaining cycle where the altered tryptophan metabolism further impairs macrophage function, locking them into a state of chronic inflammation.
This persistent inflammatory state, termed macrophage-specific SASP (mSASP), is characterized by the continuous release of inflammatory signals and a metabolic shift that is difficult to reverse. Understanding this intricate connection between tryptophan metabolism, gut health, and macrophage behavior offers exciting new avenues for developing therapies to combat the effects of aging on our immune system. Targeting elements like the gut microbiome, specific receptors (AhR), tryptophan processing pathways, and a molecule called NAD+ could be promising strategies to promote healthier aging.
Source: link to paper