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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #370366
Research Project: Exploiting Nutrition and Protein Quality Controls to Delay Age-related Macular Degeneration and Cataracts

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Mechanistic targeting of advanced glycation end-products in age-related diseases

Author
item ROWAN, SHELDON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BEJARANO-FERNANDEZ, ELOY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TAYLOR, ALLEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Biochimica et Biophysica Acta
Publication Type: Review Article
Publication Acceptance Date: 8/27/2018
Publication Date: 8/29/2018
Citation: Rowan, S., Bejarano-Fernandez, E., Taylor, A. 2018. Mechanistic targeting of advanced glycation end-products in age-related diseases. Biochimica et Biophysica Acta. 1864(12):3631-3643. https://doi.org/10.1016/j.bbadis.2018.08.036.
DOI: https://doi.org/10.1016/j.bbadis.2018.08.036

Interpretive Summary:

Technical Abstract: Glycative stress, caused by the accumulation of cytotoxic and irreversibly-formed sugar-derived advanced glycation end-products (AGEs), contributes to morbidity associated with aging, age-related diseases, and metabolic diseases. In this review, we summarize pathways leading to formation of AGEs, largely from sugars and glycolytic intermediates, and discuss detoxification of AGE precursors, including the glyoxalase system and DJ-1/Park7 deglycase. Disease pathogenesis downstream of AGE accumulation can be cell autonomous due to aggregation of glycated proteins and impaired protein function, which occurs in ocular cataracts. Extracellular AGEs also activate RAGE signaling, leading to oxidative stress, inflammation, and leukostasis in diabetic complications such as diabetic retinopathy. Pharmaceutical agents have been tested in animal models and clinically to diminish glycative burden. We summarize existing strategies and point out several new directions to diminish glycative stress including: plant-derived polyphenols as AGE inhibitors and glyoxalase inducers; improved dietary patterns, particularly Mediterranean and low glycemic diets; and enhancing proteolytic capacities of the ubiquitin-proteasome and autophagy pathways that are involved in cellular clearing of AGEs.