Resolvin D2 Treatment Increases Monocyte Production and Slows Liver Aging in Mice
Researchers here report on their exploration of a way to adjust the production of monocytes in the bone marrow, cells that become macrophages of the innate immune system. This is chiefly interesting for the lasting effect that a single treatment appears to have on the progression of liver aging in mice, leading to reduced pathology connected to inflammation, such as fibrosis. Also interesting is that providing aged bone marrow to young mice accelerates this liver pathology, by altering the generation of macrophages in the direction that induces liver pathology. Fibrosis is the excessive generation of collagen structures in the extracellular matrix, disruptive to tissue structure and function, and presently hard to treat.
Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein-coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice.
MA mice that lacked GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors.
A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice. Transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.
Is Resolvin d2 available as an oral supplement?
Given how important the liver is in aging (see Klotho), I'd assume this would have resulted in a longer overall lifespan for the mice. (Though I saw no lifespan data in the study)