Hallmarks of aging include the accumulation of aberrant proteins and a lower resistance to stresses. Because the endoplasmic reticulum (ER) functions to fold proteins and possesses unique stress sensing pathways, the central hypothesis of this dissertation is that the ER is a target of cellular aging and significantly underlies these...
The vascular endothelium is a single cell layer that lines the lumen of the entire vasculature. It is the site of synthesis of nitric oxide (NO), a vasodilatory compound synthesized by endothelial nitric oxide synthase (eNOS). NO causes intracellular calcium sequestration of the vascular smooth muscle cells, relaxing and dilating...
Oxidative stress is the major driving force behind the aging process and many age-related diseases. However, direct experimental evidence of whether antioxidants, such as ascorbate (AA) and lipoic acid (LA) can slow the progression of aging process and/or reduce risks of developing degenerative disease is largely absent. This suggests a...
Vitamin C is an essential component of the human diet. Uptake of vitamin C in the cell is regulated by the function of sodium-dependent vitamin C transporters (SVCTs). SVCT1 (encoded by the SLC23A1 gene) is expressed in the colon, liver and kidney, where it plays a vital role in determining...
Glutathione (GSH) is the predominant low molecular weight thiol antioxidant
in liver tissue. GSH plays an important role in maintaining the intracellular thiol redox
ratio as well as detoxification of electrophiles and xenobiotics. Aging leads to a significant decline (35%; P ≤ 0.05) in hepatocellular GSH levels. Using young (2-4...