氨基酸转运蛋白LAT2减少是导致衰老过程中蛋白质利用能力下降的主要原因

宋蕊, 李光, 赵亮, 仇莉丽, 秦锡雨, 张晓旭, 刘晓雪, 周君, 胡萌晓, 张力圩, 苏佳琪, 刘心娟, 王晓玉

工程（英文） ›› 2024, Vol. 42 ›› Issue (11) : 88-98.

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工程（英文） ›› 2024, Vol. 42 ›› Issue (11) : 88-98. DOI: 10.1016/j.eng.2024.08.009
研究论文

氨基酸转运蛋白LAT2减少是导致衰老过程中蛋白质利用能力下降的主要原因

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

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摘要

随着全球人口逐渐老龄化，了解老年人蛋白质利用效率的变化变得愈发重要。我们的研究深入探讨了蛋白质摄入与衰老之间的复杂联系，并着重关注了老年人的精准营养需求。通过Meta分析，我们证实了老年人蛋白质利用能力下降，并研究了植物和动物蛋白质摄入后的不同变化。在针对不同年龄小鼠的实验中，我们发现老年小鼠对四种蛋白质（酪蛋白、牛肉蛋白、大豆蛋白和谷蛋白）的利用率均有所下降，特别是对酪蛋白的表观消化率降低最为明显。因此，我们选择酪蛋白作为进一步研究的重点。通过肽组学分析和检测胃蛋白酶水平，我们发现老年小鼠的胃消化功能有所减弱，但这种减弱对整体蛋白质消化的影响并不显著。随后，我们利用氨基酸代谢组学技术发现，氨基酸的异常吸收是老年人蛋白质利用率下降的一个潜在原因，特别是支链氨基酸（BCAAs）的吸收减少。通过蛋白质组学研究，我们发现老年人和老年小鼠中的大型中性氨基酸转运蛋白2（LAT2）表达量减少了60%以上，这是导致BCAAs利用率降低的关键因素。综上所述，我们的研究揭示了LAT2在氨基酸吸收途径中对老年人蛋白质利用的重要性，并为提高老年人蛋白质利用率提供了新的理论依据。

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.

关键词

衰老 / 蛋白质利用 / 多肽 / 氨基酸 / 大型中性氨基酸转运蛋白2

Keywords

Aging / Protein utilization / Peptide / Amino acid / Large neutral amino acid transporter 2

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宋蕊, 李光, 赵亮. 氨基酸转运蛋白LAT2减少是导致衰老过程中蛋白质利用能力下降的主要原因. Engineering. 2024, 42(11): 88-98 https://doi.org/10.1016/j.eng.2024.08.009

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