Glycoxidation or advanced glycation endproducts (AGE) accelerate oxidative mechanisms, resulting in activation of transcriptional pathways, excessive proliferative/growth-related phenomena and sustained inflammation leading to clinical aging. These are further accelerated by diabetes or by conditions associated with increased production or decreased AGE clearance, eg. renal insufficiency. A major source of AGE precursors and oxidant-stress is identified to be the western diet. The turnover of AGE involves specific AGE receptors and depends on renal function. Advancing age is known to be associated with increased OS, increased prevalence of cardiovascular disease, impaired glucose tolerance, diabetes mellitus, renal decline, as well as with accumulation of AGE. While efforts have linked AGE-mediated OS and chronic complications in aging animals, human studies are strikingly lacking. We plan to test the hypotheses that: 1) older men and women (age 60+ years) who consume standard (high in AGE) diets will have higher serum AGE in conjunction with higher OS, and markers of vascular dysfunction or inflammation, compared to age-matched subjects consuming low in AGE diet, and to younger (<35 years) subjects, and 2) AGE-restriction, by dietary modification, will reduce the total AGE burden, oxidative and inflammatory mediators and attenuate the differences between older and younger groups.
The Specific Aims are to determine: 1) The correlation of circulating levels of defined AGE and inflammatory markers, eg. CRP, TNFa, and IL-6 in older and younger groups with the dietary intake of AGE. 2) The effect of dietary AGE restriction on AGE and AGE-dependent parameters of OS and inflammation. 3) The effect of environmental (dietary) glycotoxic burden on AGE-receptor-mediated removal mechanisms in PBMN from older and young persons. It is hoped that the data will lay the groundwork for future studies evaluating optimal methods of nutrient preparation as ways to ameliorate a major environmental promoter of pro-oxidant events, and thus aging.
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