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Decreased Amino Acid Transporter LAT2 Is the Main Determinant of Impaired Protein Utilization During Aging
Engineering ( IF 10.1 ) Pub Date : 2024-08-30 , DOI: 10.1016/j.eng.2024.08.009
Rui Song, Guang Li, Liang Zhao, Lili Qiu, Xiyu Qin, Xiaoxu Zhang, Xiaoxue Liu, Jun Zhou, Mengxiao Hu, Liwei Zhang, Jiaqi Su, Xinjuan Liu, Xiaoyu Wang

As the global demographic shifts toward an aging population, understanding the efficiency of protein utilization in older adults becomes crucial. Our study explores the intricate relationship between protein intake and aging, with a focus on precision nutrition for older people. Through a meta-analysis, we confirm a decline in protein-utilization capacity in older individuals and examine the different contributions of plant and animal protein. In experiments involving mice of different ages, older mice exhibited decreases in the biological utilization of four proteins (casein, beef protein, soy protein, and gluten), particularly casein. In subsequent research, casein was studied as a key protein. A decline in gastric digestion function was observed through peptidomics and the examination of pepsin levels using casein. Nevertheless, this decline did not significantly affect the overall protein digestion during the aging process. The combined application of targeted amino acid metabolomics identified abnormal absorption of amino acids as the underlying cause of decreased protein utilization during aging, particularly emphasizing a reduction in branched-chain amino acids (BCAAs) in older mice. Delving deeper into the proteomics of the intestinal protein digestion and absorption pathway, a reduction of over 60% in large neutral amino acid transporter 2 (LAT2) protein expression was observed in both older humans and aged mice. The reduction in LAT2 protein was found to be a key factor influencing the diminished BCAA availability. Overall, our study establishes the significance of amino acid absorption through LAT2 in protein utilization during aging and offers a new theoretical foundation for improving protein utilization in the older adults.

中文翻译:


氨基酸转运蛋白 LAT2 减少是衰老过程中蛋白质利用受损的主要决定因素



随着全球人口结构转向人口老龄化,了解老年人蛋白质利用的效率变得至关重要。我们的研究探讨了蛋白质摄入与衰老之间的复杂关系,重点是老年人的精准营养。通过荟萃分析,我们确认了老年人蛋白质利用能力的下降,并研究了植物和动物蛋白的不同贡献。在涉及不同年龄小鼠的实验中,老年小鼠表现出四种蛋白质(酪蛋白、牛肉蛋白、大豆蛋白和麸质)的生物利用降低,尤其是酪蛋白。在随后的研究中,酪蛋白被研究为一种关键蛋白。通过消化组学和使用酪蛋白检查胃蛋白酶水平观察到胃消化功能下降。尽管如此,这种下降并没有显着影响衰老过程中的整体蛋白质消化。靶向氨基酸代谢组学的联合应用确定氨基酸吸收异常是衰老过程中蛋白质利用率降低的根本原因,特别强调老年小鼠支链氨基酸 (BCAA) 的减少。深入研究肠道蛋白质消化和吸收途径的蛋白质组学,在老年人和老年小鼠中观察到大型中性氨基酸转运蛋白 2 (LAT2) 蛋白表达降低 60% 以上。发现 LAT2 蛋白的减少是影响 BCAA 可用性降低的关键因素。总体而言,我们的研究确定了通过 LAT2 吸收氨基酸对衰老过程中蛋白质利用的重要性,并为提高老年人的蛋白质利用提供了新的理论基础。
更新日期:2024-08-30
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