Surprise! Just when we thought we knew everything about vitamin C

One of the great things about following longevity research is that surprises are around every corner.  But I have not imagined a surprise of major importance about vitamin C supplementation.  Yesterday I would have said such a surprise is very unlikely because the stuff has been studied for more than 50 years including the Linus Pauling C-advocacy era.  There is a long history of controversy regarding therapeutic use of vitamin C, especially in megadose amounts(see the citations in ref).  Having been an aficionado of C megadosing back in the 70s, I have long since given up on the substance being other than an important antioxidant supplement.   Well, wrong again!  A 2010 research study just published in the FASEB Journal indicates that vitamin supplementation C cures mice with Werner’s Syndrome and could possibly be very important for the longevity of people with related genetic defects(ref)(ref).  What did we miss and what new is to be learned about vitamin C?

Werner’s Syndrome is a form of adult progeria (premature aging) due to a mutation in the WRN gene, a helicase deficiency.  For background on the disease and its genetic causes see the blog post Werner Syndrome – another model for aging.  

The new study is entitled Vitamin C restores healthy aging in a mouse model for Werner syndrome.  “Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many phenotypic features of WS, including a prooxidant status and a shorter mean life span compared to wild-type animals. Here, we show that Wrn mutant mice also develop premature liver sinusoidal endothelial defenestration along with inflammation and metabolic syndrome. Vitamin C supplementation rescued the shorter mean life span of Wrn mutant mice and reversed several age-related abnormalities in adipose tissues and liver endothelial defenestration, genomic integrity, and inflammatory status. At the molecular level, phosphorylation of age-related stress markers like Akt kinase-specific substrates and the transcription factor NF-kappaB, as well as protein kinase C and Hif-1 transcription factor levels, which are increased in the liver of Wrn mutants, were normalized by vitamin C. Vitamin C also increased the transcriptional regulator of lipid metabolism PPAR . Finally, microarray and gene set enrichment analyses on liver tissues revealed that vitamin C decreased genes normally up-regulated in human WS fibroblasts and cancers, and it increased genes involved in tissue injury response and adipocyte dedifferentiation in obese mice. Vitamin C did not have such effect on wild-type mice. These results indicate that vitamin C supplementation could be beneficial for patients with WS.”  In other words, vitamin C supplementation delivers on restoring a Wrn mutant mice to normal healthy mouse status and the researchers think it might do the same for human patients with WS.

The important implication of the study is that vitamin C could be extremely important for prolonging the lives of people with WS or related genetic defects who normally show accelerated aging around 20 and die by 50.  A discussion of the new result in EurekAlert quotes an author of the study:”Our study clearly indicates that a healthy organism or individuals with no health problems do not require a large amount of vitamin C in order to increase their lifespan, especially if they have a balanced diet and they exercise,” said Michel Lebel, Ph.D., co-author of the study from the Centre de Recherche en Cancerologie in Quebec, Canada. “An organism or individual with a mutation in the WRN gene or any gene affected by the WRN protein, and thus predisposes them to several age-related diseases, may benefit from a diet with the appropriate amount of vitamin C.”

The reports I have read of this study do not make it clear how exactly vitamin C works to overcome the multiple effects of accelerated aging  due to mutation in the WRN gene, and I suspect this is unknown.  I would like to learn more about that  since I doubt only a simple antioxidant effect is involved.  And, if we knew how vitamin C can halt extraordinary aging due to WS, that just possibly might give us a clue as to how something else could halt normal aging.

There is apparently a lot more to learn about the workings of that wonderful, familiar and cheap ascorbic acid stuff.   “Vitamin C has become one of the most misunderstood substances in our medicine cabinets and food,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “This study and others like it help explain how and why this chemical can help to defend some, but certainly not all, people from premature senescence(ref).”  

Rapidly curing a roaring case of hepatitis back in 1970 using megadoses of vitamin C is what started my interest in anti-aging science.  I will continue popping at least 3 grams a day of C as I have been doing for decades now.