Asparagine prevents intestinal stem cell aging via the autophagy‐lysosomal pathway

Abstract The age‐associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age‐related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound anti‐aging properties on ISCs. Asn inhibits the hyperproliferation of aging ISCs in Drosophila , maintains intestinal homeostasis, and extends the lifespan of aging flies. Complementarily, Asn promotes the growth and branching of elderly murine intestinal organoids, indicating its anti‐aging capacity to enhance ISC function. Mechanistic analyses have revealed that Asn exerts its effects via the activation of the autophagic signaling pathway. In summary, this study has preliminarily explored the potential supportive role of Asn in ameliorating intestinal aging, providing a foundation for further research into therapeutic interventions targeting age‐related intestinal dysfunction.