(P23-085-23) Plasma Folate as a Biomarker for Folate Status Is Not Indicative of Folate Levels in Aged Versus Young Mouse Skeletal Muscle

Objectives: According to the US Census Bureau and CDC, in 2030 more than 20% of the US population will be >65 yrs old. With a life expectancy in the US of ~78 years, Americans are living longer with increased rates of disability. A central contributor to disability is loss of muscle mass and function, which accelerates after age 60. Additionally, mitochondrial function declines with age and may precede age-related phenotypes. It is well recognized that nutrient needs change throughout the lifespan and may play a pivotal role in reducing age-related muscle declines, thus monitoring nutrient status is becoming increasingly important. The majority of nutrients are monitored through blood analyses, however understanding how nutrient biomarkers relate to tissue levels and markers of health is not well understood. The purpose of this study was to investigate folate levels in plasma, liver, and skeletal muscles from 10 and 52 wk mice consuming a folate-sufficient or folate-deficient diets.

Methods: Plasma, liver, and gastrocnemius muscles were harvested from 10 and 52 wk mice that were weaned to either AIN-93G control diet or a modified AIN-93G diet lacking folic acid. Folate levels were quantified using the L. casei microbiological assay. Skeletal muscles and liver were examined for mitochondrial DNA integrity.

Results: Total folates were reduced in 10 and 52 wk mice consuming a folate-deficient diet in plasma and liver. In gastrocnemius muscle, total folates were reduced in 10 wk mice consuming a folate-deficient diet but were elevated in 52 wk mice consuming a folate-deficient diet. Total folates in 52 wk mice were elevated by 20% in plasma, reduced by 40% in gastrocnemius muscle, and were not significantly different in liver compared to 10 wk mice on a folate-sufficient diet. Gastrocnemius muscle from 52 wk mice consuming a folate-sufficient diet had elevated levels of the mtDNA 3860 common deletion compared to 10 wk mice. Furthermore, gastrocnemius muscle from 52 wk mice consuming a folate-deficient diet had elevated levels of the mtDNA 3860 common deletion compared to mice consuming a folate-sufficient diet.

Conclusions: Our results demonstrate that plasma levels of folate are not reflective of folate status in 52 wk mouse skeletal muscle. Furthermore, age-associated reductions in skeletal muscle folates are associated with impaired mitochondrial integrity.

Funding Sources: N/A