Arranz Lorena, Naudí Alba, De la Fuente Mónica, Pamplona Reinald
Department of Physiology (Animal Physiology II), Faculty of Biological Sciences, Complutense University of Madrid, Madrid, 28040, Spain.
Age (Dordr). 2013 Jun;35(3):621-35. doi: 10.1007/s11357-012-9391-0. Epub 2012 Feb 25.
Membrane unsaturation plays an important role in the aging process and the determination of inter-species animal longevity. Furthermore, the accumulation of oxidation-derived molecular damage to cellular components particularly in the nervous and immune systems over time leads to homeostasis loss, which highly influences age-related morbidity and mortality. In this context, it is of great interest to know and discern the degree of membrane unsaturation and the steady-state levels of oxidative damage in both physiological systems from long-lived subjects. In the present work, adult (28 ± 4 weeks), old (76 ± 4 weeks) and exceptionally old (128 ± 4 weeks) BALB/c female mice were used. Brain and spleen were analysed for membrane fatty acid composition and specific markers of protein oxidation, glycoxidation and lipoxidation damage, i.e. glutamic semialdehyde, aminoadipic semialdehyde, carboxyethyl-lysine, carboxymethyl-lysine and malondialdehyde-lysine, by gas chromatography-mass spectrometry. The results showed significantly lower peroxidizability index in brain and spleen from exceptionally old animals when compared to old specimens. The higher membrane resistance to lipid peroxidation and lower lipoxidation-derived molecular damage found in exceptionally old animals was associated with a significantly lower desaturase activity and peroxisomal β-oxidation. Protein oxidation markers in brain and spleen from adult and exceptionally old animals showed similar levels, which were higher in old mice. In addition, the higher levels of the glycoxidation-derived marker observed in exceptionally old animals, as well as in adult mice, could be considered as a good indicator of a better bioenergetic state of these animals when compared to the old group. In conclusion, low lipid oxidation susceptibility and maintenance of adult-like protein lipoxidative damage could be key mechanisms for longevity achievement.
膜不饱和状态在衰老过程以及不同物种间动物寿命的决定中起着重要作用。此外，随着时间推移，氧化衍生的分子对细胞成分尤其是神经和免疫系统的损伤积累会导致体内稳态丧失，这对与年龄相关的发病率和死亡率有很大影响。在这种情况下，了解和辨别长寿个体这两个生理系统中的膜不饱和程度以及氧化损伤的稳态水平非常有趣。在本研究中，使用了成年（28±4周）、老年（76±4周）和极老龄（128±4周）的BALB/c雌性小鼠。通过气相色谱 - 质谱法分析脑和脾脏的膜脂肪酸组成以及蛋白质氧化、糖氧化和脂氧化损伤的特定标志物，即谷氨酸半醛、氨基己二酸半醛、羧乙基赖氨酸、羧甲基赖氨酸和丙二醛赖氨酸。结果显示，与老年小鼠相比，极老龄动物脑和脾脏中的过氧化性指数显著降低。极老龄动物中发现的对脂质过氧化的较高膜抗性和较低的脂氧化衍生分子损伤与显著较低的去饱和酶活性和过氧化物酶体β - 氧化有关。成年和极老龄动物脑和脾脏中的蛋白质氧化标志物水平相似，老年小鼠中的水平更高。此外，与老年组相比，极老龄动物以及成年小鼠中观察到的糖氧化衍生标志物的较高水平可被视为这些动物具有更好生物能量状态的良好指标。总之，低脂质氧化敏感性和维持类似成年个体的蛋白质脂氧化损伤可能是实现长寿的关键机制。
