Lifelong caloric restriction alters hepatic lipid mediator profiles in aging mice, associated with epoxide-diol pathway changes.

Researchers compared liver oxylipin (lipid mediator) profiles between ad libitum-fed and calorie-restricted mice across adulthood and aging. Ad libitum-fed mice showed a shift toward pro-inflammatory oxylipins around 9 months, followed by depletion of cytoprotective epoxides and accumulation of diols in later life. Caloric restriction blunted these inflammatory shifts, preserved epoxy-fatty acids, and induced CYB5R3, an enzyme that may sustain epoxide production despite reduced overall enzyme levels.