Moon Lily, Frederick David W, Baur Joseph A, Li Lin Z
Molecular Imaging Laboratory, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adv Exp Med Biol. 2017;977:51-57. doi: 10.1007/978-3-319-55231-6_8.
Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD) and the NAD-coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD/NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively. The redox ratio, i.e., the ratio of Fp to NADH, may be a surrogate indicator of the NAD/NADH redox potential. In this study we used the Chance redox scanner (NADH/Fp fluorescence imaging at low temperature) to investigate the effect of aging on the redox state of mitochondria in skeletal muscles. The results showed that there are borderline significant differences in nominal concentrations of Fp and NADH, but not in the redox ratio s when comparing 3.5-month and 13-month old muscles of mice (n = 6). It may be necessary to increase the number of muscle samples and study mice of more advanced age.
衰老是许多疾病的最大风险因素。细胞内烟酰胺腺嘌呤二核苷酸(NAD)的浓度以及NAD偶联的氧化还原状态被认为可调节许多与衰老相关的过程,但其具体机制仍不清楚。骨骼肌中NAD的浓度会随着年龄增长而下降,但对于衰老会增加还是降低NAD/NADH的氧化还原电位,目前尚无定论。氧化型黄素基团(Fp)(例如黄素蛋白中含有的黄素腺嘌呤二核苷酸FAD)和NADH分别是组织氧化和还原状态的固有荧光指示剂。氧化还原比,即Fp与NADH的比值,可能是NAD/NADH氧化还原电位的替代指标。在本研究中,我们使用了Chance氧化还原扫描仪(低温下的NADH/Fp荧光成像)来研究衰老对骨骼肌线粒体氧化还原状态的影响。结果显示,在比较3.5月龄和13月龄小鼠的肌肉(n = 6)时,Fp和NADH的名义浓度存在临界显著差异,但氧化还原比没有差异。可能有必要增加肌肉样本数量并研究更老龄的小鼠。