Carbohydrates are crucial molecules that are used for various cellular processes, including energy production. However, carbohydrate utilization should be properly controlled, as abnormal regulation of carbohydrate metabolism is associated with diseases, such as diabetes, cardiovascular diseases, and stroke.  High glucose treatments have negative effects on aging in human endothelial cells and fibroblasts. In these human cells, treatment with high glucose accelerates various aging-related phenotypes, such as increased levels of senescence-associated (SA) b-gal staining, reduced proliferation, irregular morphology, and increased ROS levels. One mechanism by which glucose-enriched diets shorten the lifespan is through down-regulation of DAF-16/FOXO and HSF-1 transcription factors in IIS. Glucose-rich diets reduce the lifespan of wild-type worms, but do not further decrease the short lifespan of daf-16/FOXO or hsf-1 mutant worms. In addition, sirtuins (Sir2-like proteins: SIRTs) appear to mediate glucose-induced accelerated cellular aging. SIRTs are NAD+-dependent protein deacetylases implicated in the aging of many organisms. Glucose treatments down-regulate SIRTs and FOXO1. Conversely, treatment with a SIRT1 activator or SIRT3 overexpression restores FOXO1 activity and delays glucose-induced accelerated aging.  High glucose also accelerates the senescence of human endothelial progenitor cells (EPCs) by activating p38 mitogen-activated protein kinase (MAPK). Under glucose-rich conditions, cellular aging phenotypes, such as increased levels of SA b-gal staining and reduced cellular proliferation, are observed in EPCs, and p38 MAPK is activated. These aging phenotypes are restored by treatment with a p38 MAPK inhibitor, suggesting that p38 MAPK mediates the pro-aging effects of high glucose. There were also identified other genes and pathways that would mediate the acceleration of aging effects of high carbohydrate diets such as insulin/ IGF-1 signaling, MED15 (Mediator of RNA polymerase II transcription subunit 15) and SREBPs (major fat metabolism-regulatory transcription factors).  In conclusion, several studies identified that high glucose treatments accelerate senescence in cultured human endothelial cells and fibroblasts.