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Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression
Author(s) -
Li Yuanyuan,
Liu Liang,
Tollefsbol Trygve O.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-149328
Subject(s) - telomerase reverse transcriptase , epigenetics , biology , dna methylation , cancer cell , chromatin , telomerase , cancer research , gene expression , microbiology and biotechnology , cancer , gene , genetics
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.—Li, Y., Liu, L., Tollefsbol, T. O. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J. 24, 1442–1453 (2010). www.fasebj.org