Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans

Age (Dordr). 2015 Dec;37(6):113. doi: 10.1007/s11357-015-9850-5. Epub 2015 Nov 6.


Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments.

Keywords: Aging; Caenorhabditis elegans; Dietary restriction; Folic acid; Oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • Folic Acid / administration & dosage*
  • Folic Acid / pharmacology*
  • Forkhead Transcription Factors / metabolism
  • Glutathione Transferase / metabolism
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Longevity / drug effects*
  • Microscopy, Fluorescence
  • Models, Animal
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Sirtuins / metabolism
  • Superoxide Dismutase / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Transcription Factors
  • daf-16 protein, C elegans
  • skn-1 protein, C elegans
  • Insulin-Like Growth Factor I
  • Folic Acid
  • Superoxide Dismutase
  • Glutathione Transferase
  • TOR Serine-Threonine Kinases
  • SIR-2.1 protein, C elegans
  • Sirtuins