Low fatty acid unsaturation: A mechanism for lowered lipoperoxidative modification of tissue proteins in mammalian species with long life spans

dCarbonyl compounds generated by the nonenzymatic oxidation of polyunsatura ted fatty acids react with nucleophilic groups in proteins, leading to thei r modification. It has not been tested whether fatty acid unsaturation is r elated to steady-state levels of lipoxidation-derived protein modification in vivo. A low fatty acid unsaturation, hence a low protein lipoxidation, i n tissues of longevous animals would be consistent with the free radical th eory of aging, because membrane lipids increase their sensitivity to oxidat ive damage as a function of their degree of unsaturation. To evaluate the r elationship between fatty acid composition, protein lipoxidation, and maxim um life span (MLSP), we analyzed liver fatty acids and proteins from seven mammalian species, ranging in MLSP from 3.5 to 46 years. The results show t hat the peroxidizability index of fatty acids and the sensitivity to in vit ro lipid peroxidation are negatively correlated with the MLSP. Based on gas chromatography and mass spectroscopy analyses, liver proteins of all these species contain malondialdehyde-lysine and N'-carboxymethyllysine adducts, two biomarkers of protein lipoxidation. The steady-state levels of malondi aldehyde-14 sine and N'-carboxymethyl lysine are directly related to the pe roxidizability index and inversely related to the MLSP. We propose that a l ow degree of fatty acid unsaturation may have been selected in longevous ma mmals to protect their tissue lipids and proteins against oxidative damage while maintaining an appropriate environment fur membrane function.