Cell· 2026Q1
Fatty acid desaturation controls cellular fate decisions between senescence and ferroptosis
- 1citations
- Q1SCImago
- 2026year
Short summary
Dihomo-gamma-linolenic acid (DGLA) levels dictate whether cells undergo senescence or ferroptosis, with reduced DGLA promoting ferroptosis and senescent cells showing reduced DGLA. Oral DGLA supplementation reduced senescent cell burden in aged mice.
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Key points
- Senescent cells have reduced levels of the polyunsaturated fatty acid DGLA (20:3 ω-3).
- Exogenous DGLA repletion or inhibition of its metabolizing enzyme (delta-5-desaturase) induces ferroptosis.
- Oral DGLA supplementation reduced senescent cell burden and improved functional outcomes in aged mice.
- Obese humans with lower DGLA desaturation rates showed reduced markers of adipose tissue senescence.
AI-generated from the title and abstract; the full text is not read.
Abstract
Summary When subject to damage or stress, cells develop responses in order to maintain tissue homeostasis. Two such decisions are ferroptosis and cellular senescence, but how cells decide between these outcomes remains unclear. Here we show that senescent cells increase levels of multiple membrane-bound polyunsaturated fatty acids (PUFAs), but a specific PUFA, dihomo-gamma-linolenic acid (DGLA, 20:3 ω -3) is reduced. Exogenous repletion of DGLA or inhibition of delta-5-desaturase, the enzyme that metabolizes DGLA, instead results in cell death by ferroptosis. Senescent cells had elevated levels of other fezzroptosis sensitizers, including labile iron and expression of lipoxygenases – but also increased Gpx4 levels to prevent ferroptosis. Oral DGLA lowered senescent cell burden in aged mice and improved age-related functional outcomes. Finally, obese humans with lowered DGLA desaturation rates showed lower markers of adipose tissue senescence. Together, our data implicate DGLA and its desaturation as a major driver of decisions between senescence and ferroptosis.
The authors' abstract, as published at the source. Cell, 2026 · DOI ↗
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Field: Pulmonary and Respiratory Medicine
Pulmonary and Respiratory MedicineMedicine