Age-dependent changes of L-valine

As an essential amino acid, the absorption of L-valine in the mouse intestine relies on the transport system of intestinal epithelial cells. This uptake capacity exhibits significant age-dependent changes as mice age, with the core mechanisms closely linked to the maturation of intestinal epithelial cells, the regulatory expression of transport carriers, and changes in the intestinal physiological environment.

In newborn mice (within 1-2 weeks after birth), intestinal epithelial cells are not fully mature: the villi are short and sparse, and the intestinal barrier function is weak. At this stage, L-valine uptake mainly depends on passive diffusion and low-affinity transport systems (such as certain non-specific amino acid transporters), resulting in overall low uptake efficiency. During this period, mice primarily obtain nutrients from breast milk, which has a high amino acid concentration—passive diffusion is sufficient to meet early growth needs. Meanwhile, the active transport mechanism of intestinal epithelial cells is not fully activated, and the mRNA and protein expression levels of related carriers (e.g., the L-type amino acid transporter LAT1) remain at a basal state.

As mice enter the juvenile stage (2-4 weeks), the intestine develops rapidly: villi lengthen, crypts deepen, and intestinal epithelial cell differentiation becomes complete. The active transport system gradually becomes the dominant mode of L-valine uptake. During this period, the expression of high-affinity transporters such as LAT1 and LAT2 is significantly upregulated. These carriers, mainly distributed on the brush border membrane of intestinal epithelial cells, efficiently take up L-valine through a synergistic transport mechanism with sodium or hydrogen ions. Additionally, juvenile mice are in a peak growth period with a surge in amino acid demand; the enhanced metabolic activity of intestinal epithelial cells provides sufficient energy and material basis for the synthesis and function of transport carriers, pushing the uptake rate and capacity of L-valine to their peak.

In adulthood (after 8 weeks), the structure and function of the mouse intestine stabilize, and L-valine uptake remains at a relatively constant level. At this stage, the expression of transport carriers is stable but may be finely adjusted by factors such as diet and hormone levels. For example, a long-term high-protein diet can moderately upregulate LAT1 expression to enhance amino acid uptake; hormones like insulin may also affect carrier activity through signaling pathways, ensuring that L-valine uptake matches the body’s metabolic needs. The renewal rate of intestinal epithelial cells in adult mice is stable, with a complete turnover every 3-5 days. Newly differentiated cells maintain mature transport functions, keeping the overall uptake efficiency in balance.

When mice enter old age (over 18 months), intestinal function gradually declines, and L-valine uptake capacity tends to decrease. On one hand, intestinal villi atrophy and the integrity of epithelial cells is impaired, reducing the distribution area of transport carriers. On the other hand, aging-related oxidative stress and inflammatory responses can inhibit the synthesis and activity of transport carriers—for instance, LAT1 expression decreases, and its binding affinity for L-valine declines. Furthermore, the weakened activity of digestive enzymes in the intestines of elderly mice reduces the release rate of amino acids, indirectly affecting the uptake efficiency of L-valine by intestinal epithelial cells. Meanwhile, changes in the intestinal flora structure may affect epithelial cell function through metabolites, further exacerbating the decline in uptake capacity.

This age-dependent change is essentially a result of the body adapting to the needs of different growth stages: efficient uptake in the juvenile stage meets the energy and material demands of growth and development; stable uptake in adulthood maintains metabolic balance; and the decline in uptake in old age corresponds to the overall decline in physiological functions. In-depth research on this changing pattern helps understand the nutritional metabolism characteristics of mice at different ages, providing a theoretical basis for nutritional interventions in elderly animals or studies on disease models.