氨基酸转运蛋白LAT2的减少导致衰老过程中蛋白质利用受损

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) : 95 -106.

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工程(英文) ›› 2024, Vol. 42 ›› Issue (11) : 95 -106. DOI: 10.1016/j.eng.2024.08.009
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氨基酸转运蛋白LAT2的减少导致衰老过程中蛋白质利用受损

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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

随着全球人口老龄化加剧,明确老年人蛋白质利用效率变得愈发重要。本文探究了蛋白质摄入与衰老之间的复杂联系,并重点关注老年人的精准营养需求。首先,本研究通过meta分析证实了老年人蛋白质利用效率下降,并明确了对植物与动物蛋白质的利用率存在差异。利用衰老小鼠模型研究发现,老年小鼠对酪蛋白、牛肉蛋白、大豆蛋白和谷蛋白的生物利用率均下降,其中酪蛋白的利用率下降最为显著。因此,后续重点研究衰老对酪蛋白消化吸收的影响。通过肽组学和胃蛋白酶水平检测等,发现老年小鼠胃的消化功能下降,然而这对衰老过程中整体蛋白质消化的影响不显著。进一步应用靶向氨基酸代谢组学,确认了老年小鼠中支链氨基酸(BCAAs)的吸收显著减少,表明氨基酸的吸收异常可能是衰老过程中蛋白质利用率下降的潜在原因。因此,进一步对肠道上皮细胞进行蛋白质组学分析,结果显示在老年人和老年小鼠中,大型中性氨基酸转运蛋白2(LAT2)的表达量减少了约60%,表明LAT2的减少可能是导致BCAAs利用率降低的关键因素。综上所述,本研究明确了LAT2介导的氨基酸吸收途径在衰老过程中对蛋白质利用的重要意义,为老年人蛋白质的高效利用提供新的理论依据。

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

Key words

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

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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 氨基酸转运蛋白LAT2的减少导致衰老过程中蛋白质利用受损[J]. 工程(英文), 2024, 42(11): 95-106 DOI:10.1016/j.eng.2024.08.009

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