Fatty acid changes influence whether cells become old or die from iron-related damage

Senescent cells increase levels of multiple polyunsaturated fatty acids while reducing levels of dihomo-gamma-linolenic acid (DGLA).

• Exogenous DGLA supplementation leads to cell death by ferroptosis.
• Senescent cells show features associated with ferroptosis, including labile iron and low-level membrane peroxidation.
• Oral DGLA supplementation reduces markers of senescence in aged mice and enhances age-related functional outcomes.
• Obese humans with lower DGLA desaturation rates exhibit reduced markers of adipose tissue senescence.
• Shifts in polyunsaturated fatty acid metabolism may influence the decision between senescence and ferroptosis.

Simplified