This review of literature and our data suggests that up-regulated production of interferon-gamma (IFNG) in periphery and brain triggers a merger of tryptophan (TRY)-kynurenine (KYN) and guanine-tetrahydrobiopterin (BH4) metabolic pathways into inflammation cascade involved in aging and aging-associated medical and psychiatric disorders (AAMPD) (metabolic syndrome, depression, vascular cognitive impairment).
The combination of high promoter T of (IFN-gamma) + 874(T/A) with high promoter A of (TNF-alpha) -308(G/A) might "superinduce" IDO and cause (or contribute to) inflammation of brain microvessels detected as white matter hyperintensities and leading to VCI development.