Accumulation of Nε-(carboxyethyl) lysine in Caenorhabditis elegans is correlated with the formation of ketone body.

ABSTRACT

Advanced glycation end-products (AGEs) are formed when proteins react with carbonyl compounds, and they gradually accumulate with age. However, AGE accumulation with ageing is not fully understood because longevity studies in mammals are time-consuming. Therefore, we used Caenorhabditis elegans to evaluate the correlation between ageing and AGE accumulation. Age-synchronized C.elegans nematodes were cultured for 3 and 12 days. The levels of Nε-(carboxymethyl) lysine, Nω-(carboxymethyl) arginine, Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl) ornithine and Nε-(carboxyethyl) lysine (CEL) were compared. Glucose, methylglyoxal and acetol were incubated with human serum albumin, and CEL formation was evaluated. The levels of methylglyoxal and ketone bodies in C.elegans were quantified. CEL accumulation increased significantly with culture duration. Methylglyoxal and ketone bodies-possible forerunners of AGE accumulation-were also quantified with respect to culture duration. The levels of ketone bodies increased significantly during culture, and correlated closely with CEL accumulation (R2 = 0.72, P = 0.0008), whereas the levels of methylglyoxal did not increase over time. CEL was formed in vitro in a time-dependent manner from methylglyoxal and acetol when incubated with human serum albumin (HSA) at the same temperature as C.elegans culture, suggesting that increased levels of CEL in C.elegans are attributable to ketone bodies.