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These targeted signaling molecules are either part of a signaling cascade, or transcription factor, or an enzyme that further generates signaling mediators (e -TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner

The decline of NAD + with age results from three converging factors: (1) increased activity of CD38, a NADase whose expression increases with age-related chronic inflammation (inflammaging), (2) reduced biosynthesis via the NAMPT (nicotinamide phosphoribosyltransferase) and NMN pathways, and (3) increased demand for NAD+ by PARP-1 to repair increasing oxidative DNA damage