Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging.
BACKGROUND
Oxidative stress (OS) and inflammatory mediators increase with aging. The levels of advanced glycation endproducts (AGEs), prooxidant factors linked to chronic diseases such as diabetes, cardiovascular disease, and renal disease, also increase with aging. AGEs are readily derived from heat-treated foods. We propose that the excess consumption of certain AGEs via the diet enhances OS and inflammatory responses in healthy adults, especially in elderly persons.


METHODS
We examined 172 young (<45 years old) and older (>60 years old) healthy individuals to determine whether the concentration of specific serum AGEs (N(epsilon)-carboxymethyl-lysine [CML] or methylglyoxal [MG] derivatives) were higher in older compared to younger persons and whether, independent of age, they correlated with the intake of dietary AGEs, as well as with circulating markers of OS and inflammation.


RESULTS
Body weight, body mass index (BMI), and serum AGE, CML, and MG derivatives were higher in older participants, independent of gender. Serum CML correlated with levels of 8-isoprostanes (r = 0.448, p =.0001) as well as with Homeostasis Model Assessment index (HOMA), an index of insulin resistance (r = 0.247, p =.044). The consumption of dietary AGEs, but not of calories, correlated independently with circulating AGEs (CML: r = 0.415, p =.0001 and MG: r = 0.282, p =.002) as well as with high sensitivity C-reactive protein (hsCRP) (r = 0.200, p =.042).


CONCLUSIONS
Circulating indicators of AGEs (CML and MG derivatives), although elevated in older participants, correlate with indicators of inflammation and OS across all ages. Indicators of both AGEs and OS are directly influenced by the intake of dietary AGEs, independent of age or energy intake. Thus, reduced consumption of these oxidants may prove a safe economic policy to prevent age-related diseases, especially in an aging population.
Uribarri
Jaime
J
Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Cai
Weijing
W
Peppa
Melpomeni
M
Goodman
Susan
S
Ferrucci
Luigi
L
Striker
Gary
G
Vlassara
Helen
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D004032:Diet; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D002149:Energy Intake; D005260:Female; D017127:Glycation End Products, Advanced / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000031:analogs & derivatives
D017127:Glycation End Products, Advanced; C075750:8-epi-prostaglandin F2alpha; C048496:N(6)-carboxymethyllysine; D011765:Pyruvaldehyde; D002097:C-Reactive Protein; D015237:Dinoprost; D008239:Lysine