Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging

Abstract

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.

Figure 1

Levels of serum advanced glycation endproducts (AGEs), carboxymethyl-lysine (sCML) and methylglyoxal (sMG) derivatives are elevated in older men and women. Fasting blood was obtained in older (60–80 years old [y.o.]) and younger (18–45 y.o.) healthy participants for measurement of CML and MG derivatives, by enzyme-linked immunosorbent assay, as described. Data, representing the average of triplicate values, are shown as mean ± standard error of the mean, *p < .05.

Figure 2

Serum carboxymethyl-lysine (sCML) levels are highly associated with levels of serum methylglyoxal derivatives (sMG). Fasting fresh blood samples obtained from study participants were used for assessment of CML and MG derivatives, by enzyme-linked immunosorbent assay. Data, representing triplicate values, are shown as linear correlations.

Figure 3

Serum carboxymethyl-lysine (sCML) levels are associated with plasma 8-isoprostane. Fasting fresh blood samples obtained from study participants were used for assessment of CML and plasma 8-isoprostanes, as described. Data are shown as linear correlations.

Figure 4

Dietary intake of advanced glycation endproducts (AGEs) is associated with circulating levels of carboxymethyl-lysine (CML) and methylglyoxal (MG) derivatives. Fasting fresh blood samples obtained from study participants were used for assessment of CML (A) and MG derivatives (B). Daily consumption of AGEs was assessed based on 3-day food records as described, and data are expressed as equivalents of AGE/d (1 Eq = 1 × 10³ kU AGE). Data, indicating triplicate values, are shown as linear correlations.