Age-related alterations in fatty acid metabolism: a clinical study of erythrocyte and plasma profiles in a population from Brandenburg, Germany

Introduction: Aging is accompanied by changes in lipid metabolism that may influence cellular homeostasis and risk for age-related disease. Circulating polyunsaturated fatty acid (PUFA) status is increasingly recognized as an important marker of metabolic health and may shift with age. Product-to-precursor ratios of fatty acids, including PUFA are commonly used as proxy indices of desaturation and elongation but do not directly reflect enzyme activity. Methods: In this cross-sectional study, plasma and erythrocyte fatty acid profiles were measured by gas chromatography-flame ionization detection (GC-FID) in patients (n = 1277) from a metabolic disease clinic in Brandenburg, Germany. Participants were stratified into five age groups (≤ 34, 35-44, 45-54, 55-64, ≥ 65 years) and differences between groups were assessed using statistical tests. Results: Participants aged ≥ 65 years had higher total omega-3 (n-3) and lower total omega-6 (n-6) PUFA levels in both matrices. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased with age, whereas linoleic acid (LA) and dihomo-gamma-linolenic acid (DGLA) decreased. Ratio-based indices showed consistent age associations. The delta-5-desaturase index (D5D) and arachidonic acid (AA)/LA ratio were positively associated with age, while elongation of very long chain fatty acids (ELOVL)2 and ELOVL6 were inversely associated. Discussion: Overall, blood PUFA profiles and multiple ratio-based indices showed consistent, age-related trends in this clinical cohort. Interpretation is limited by the cross-sectional design and the lack of key determinants of PUFA status (e.g., diet, clinical covariates, genetic information and gut/microbiome factors). Nevertheless, these results underscore age-related shifts in PUFA composition and enzymatic proxy indices, providing new insights into lipid metabolism across the lifespan.