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

Exploring the utilization of casein, which is lowest during aging, revealed that peptide release in the gastrointestinal tract stabilized in older mice, primarily due to a decrease in amino acid absorption through LAT2. 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.