Social isolation of aged mice drives dramatic release of inflammatory lipoxygenase-derived oxylipins

Abstract Oxylipins, signalling molecules derived from polyunsaturated fatty acids, act as key mediators controlling inflammatory processes. Ageing fuels the disruption of this network, promoting inflammageing. Social isolation, a common feature of ageing, may contribute to the emergence of pro-inflammatory responses, further aggravating conditions like cognitive decline and frailty. Here, we studied how repeated social isolation impacts inflammation-related oxylipin profiles in seven different organs and serum of aged mice. Additionally, we explored physical exercise as a tool to ameliorate age- and isolation-associated inflammation. Our results show that social isolation induces significant increases in interleukin-1β levels and stimulates a dramatic production of lipoxygenase (LOX)-derived oxylipins in an organ-dependent manner, particularly pronounced in liver, lung, and spleen. Physical exercise failed to mitigate the pro-inflammatory effects induced by social isolation. These effects did not occur in the circulatory system as serum oxylipin levels remained relatively unchanged by isolation. The unexpected and striking elevation of oxylipins across the organs highlights the detrimental effect of social isolation and proposes key roles of oxylipins in stress-related inflammageing.