Decreased Amino Acid Transporter LAT2 Is the Main Determinant of Impaired Protein Utilization During Aging

IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Engineering Pub Date : 2024-11-01 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
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Abstract

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.

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氨基酸转运体 LAT2 减少是衰老过程中蛋白质利用受损的主要决定因素
随着全球人口向老龄化转变,了解老年人利用蛋白质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错综复杂的关系,重点关注老年人的精准营养。通过荟萃分析,我们证实了老年人蛋白质利用能力的下降,并研究了植物蛋白和动物蛋白的不同贡献。在涉及不同年龄小鼠的实验中,老年小鼠对四种蛋白质(酪蛋白、牛肉蛋白、大豆蛋白和麸质)的生物利用率都有所下降,尤其是酪蛋白。在随后的研究中,酪蛋白被作为一种关键蛋白质进行研究。通过肽组学和使用酪蛋白检测胃蛋白酶水平,观察到胃消化功能下降。尽管如此,这种下降并没有明显影响衰老过程中蛋白质的整体消化。氨基酸代谢组学的综合应用确定了氨基酸吸收异常是衰老过程中蛋白质利用率下降的根本原因,特别强调了老年小鼠支链氨基酸(BCAAs)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发现,在老年人和老龄小鼠体内,大中性氨基酸转运体 2 (LAT2) 蛋白表达量减少了 60% 以上。研究发现,LAT2 蛋白的减少是影响 BCAA 可用性降低的一个关键因素。总之,我们的研究证实了在衰老过程中通过 LAT2 吸收氨基酸对蛋白质利用的重要性,并为提高老年人对蛋白质的利用率提供了新的理论基础。
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来源期刊
Engineering
Engineering Environmental Science-Environmental Engineering
自引率
1.60%
发文量
335
审稿时长
35 days
期刊介绍: Engineering, an international open-access journal initiated by the Chinese Academy of Engineering (CAE) in 2015, serves as a distinguished platform for disseminating cutting-edge advancements in engineering R&D, sharing major research outputs, and highlighting key achievements worldwide. The journal's objectives encompass reporting progress in engineering science, fostering discussions on hot topics, addressing areas of interest, challenges, and prospects in engineering development, while considering human and environmental well-being and ethics in engineering. It aims to inspire breakthroughs and innovations with profound economic and social significance, propelling them to advanced international standards and transforming them into a new productive force. Ultimately, this endeavor seeks to bring about positive changes globally, benefit humanity, and shape a new future.
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