"ScienceDaily (Dec. 26, 2009) - Going back for a second dessert after your holiday meal might not be the best strategy for living a long, cancer-free life say researchers from the University of Alabama at Birmingham. That's because they've shown exactly how restricted calorie diets -- specifically in the form of restricted glucose -- help human cells live longer.
They found that the normal cells lived longer, and many of the precancerous cells died, when given less glucose. Gene activity was also measured under these same conditions. The reduced glucose caused normal cells to have a higher activity of the gene that dictates the level of telomerase, an enzyme that extends their lifespan and lower activity of a gene (p16) that slows their growth. Epigenetic effects (effects not due to gene mutations) were found to be a major cause in changing the activity of these genes as they reacted to decreased glucose levels.
"Western science is on the cusp of developing a pharmaceutical fountain of youth" said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This study confirms that we are on the path to persuading human cells to let us to live longer, and perhaps cancer-free, lives.""
Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression.
Li Y, Liu L, Tollefsbol TO.
FASEB J. 2009 Dec 17. [Epub ahead of print]
PMID: 20019239
doi: 10.1096/fj.09-149328
Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16(INK4a). Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. The altered gene expression was partly due to glucose restriction-induced DNA methylation changes and chromatin remodeling of the hTERT and p16 promoters in normal and immortalized WI-38 cells. Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches.