Aging and FADS1 polymorphisms decrease the biosynthetic capacity of long-chain PUFAs: A human trial using...

Area of Science:

• Biochemistry
• Human Physiology
• Genetics

Background:

• Long-chain polyunsaturated fatty acids (LCPUFAs) are essential components of cell membranes.
• Previous observations suggest aging and FADS gene variations influence LCPUFA synthesis.
• Direct quantification methods are needed to assess LCPUFA biosynthetic capacity.

Purpose of the Study:

• To investigate the combined effects of aging and FADS1 polymorphisms on LCPUFA biosynthetic capacity.
• To directly measure the conversion of linoleic acid to its metabolites using stable isotope labeling.
• To determine if aging exacerbates the impact of FADS1 polymorphisms on LCPUFA production.

Main Methods:

• Healthy young and elderly participants received a dose of [U-¹³C]linoleic acid.
• Plasma concentrations of ¹³C-labeled metabolites, including arachidonic acid (ARA), were monitored over 14 days.
• The influence of the FADS1 rs174547 polymorphism on ¹³C-ARA formation was analyzed.

Main Results:

• Maximum plasma concentration of ¹³C-arachidonic acid (ARA) was observed between 4-5 days post-administration.
• The area under the curve for ¹³C-ARA concentration significantly differed based on FADS1 rs174547 genotype (TT > TC > CC).
• Elderly individuals carrying the C allele showed a 32% reduction in ¹³C-ARA formation compared to younger carriers.

Conclusions:

• This study provides the first direct evidence that FADS1 polymorphisms regulate LCPUFA biosynthetic capacity.
• Aging significantly decreases LCPUFA biosynthetic capacity, particularly in individuals carrying the FADS1 C allele.
• Findings highlight the interplay between genetics and aging in determining essential fatty acid metabolism.