Figure 1. Hypothesized mechanisms of the role of lipids in brain aging.

Lower levels of short-chain acylcarnitines were associated with accelerated brain aging in women. Lower acylcarnitine levels suggest lower mitochondrial function, as acylcarnitines are transported from the inner mitochondrial membrane into the matrix and can influence oxidative phosphorylation (red box). In contrast, high levels of long-chain ceramides and very long-chain triglycerides were associated with accelerated brain aging in men. Long-chain ceramides can permeabilize and damage mitochondria, leading to a decrease in electron transport chain activity. Thus, in both cases, the adverse effect on the brain may be explained by mitochondrial dysfunction, but with different mechanisms in men and women.