NAD+ regulates macrophage TGFB1 silencing

A proposed theory asks whether ageing can make human macrophages, immune cells that help resolve inflammation, also release transforming growth factor beta 1, a signal linked to tissue scarring. The test would treat aged human macrophages with NMN, a molecule intended to replenish the cellular cofactor NAD+, for 48 hours before specialized pro-resolving mediators drive a healing-like state. It predicts that NAD+ enables SIRT6, a gene-regulating protein, to silence the TGFB1 gene and cut secreted signal by more than 50%. Adding OSS_128167, a SIRT6 inhibitor, should erase that predicted NMN effect. Measurements of secreted signal and gene-associated chromatin changes would test this mechanism against alternatives involving DNA methylation, the surrounding matrix, stiffness, or a cell-surface receptor.