Research Spotlight: Riboflavin Depletion Leads to a 30% Extension in Lifespan in C. Elegans

Armen Yerevanian, MD, a physician-investigator in the Division of Endocrinology at Massachusetts General Hospital, is the lead author of a new study in Aging Cell, Riboflavin Depletion Promotes Longevity and Metabolic Hormesis in Caenorhabditis elegans.

What was the question you were investigating with this study ?

We wished to examine the energetic and stress responses of depleting the essential vitamin riboflavin on the physiology of the worm C. elegans, which is a model animal to study lifespan and metabolism.

What are two or three key takeaways?

• We were able to genetically deplete the animal of riboflavin by 90%. This paradoxically led to a 30% extension in lifespan. The animals not only lived longer but were healthy and active despite having such low levels of this key vitamin.
• The animals exhibited a phenotype similar to dietary restriction even though they consumed a normal amount of food.

What were your conclusions?

We identified a new paradigm for lifespan extension that promotes a favorable energetic state and mimics dietary restriction. This is the first work to show that active depletion rather than supplementation of vitamins provides a health benefit to the animal.

What are the potential clinical implications of your work?

This work revealed the activation of conserved pathways such as FOXO and AMPK during riboflavin depletion, which are known to provide protective health effects in animals. This work opens the opportunity to explore whether selective riboflavin depletion can activate such pathways for favorable energetics and stress responses in humans. Mammals (including humans) share the same machinery for absorbing and maintaining riboflavin stores, and manipulation of this machinery can be used to study tissue-specific methods of inducing riboflavin depletion and targeting aging related metabolic diseases such as Type 2 diabetes and fatty liver.

Alexander Soukas, MD, PhD, a physician-investigator in the Center for Genomic Division at Mass General and Weissman Family MGH Research Scholar 2018-2023, is the corresponding author of the study.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.