Core Viewpoint - The research published in Nature Aging highlights the role of the glycolytic metabolite phosphoenolpyruvate (PEP) in promoting healthy aging by limiting cGAS-driven inflammation, suggesting PEP as a promising intervention for aging and age-related diseases [2][3][6]. Group 1: Research Findings - PEP accumulation is defined as an evolutionarily conserved protective mechanism against aging, with external supplementation of PEP alleviating neuroinflammation and improving cognitive function in Alzheimer's disease mouse models [3][6]. - Longitudinal analyses in mice and humans show that PEP levels exhibit a biphasic change with age, initially increasing and then decreasing, where blocking PEP accumulation exacerbates inflammation and accelerates aging phenotypes [5][6]. - In elderly populations, higher levels of PEP correlate significantly with lower inflammation levels and healthier characteristics [5]. Group 2: Mechanism of Action - PEP acts as an endogenous inhibitor of the cGAS-STING inflammatory signaling pathway by competitively binding to cGAS, functioning as a "natural anti-inflammatory" produced by the body [6]. - The study provides a metabolic explanation for the occurrence of inflammation-related aging and neurodegeneration, as indicated by the dual fluctuation of PEP levels during aging [7].