Beschreibung:
<jats:title>Summary</jats:title><jats:p>Cellular metabolism is regulated by the <jats:styled-content style="fixed-case">mTOR</jats:styled-content> kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The <jats:styled-content style="fixed-case">mTOR</jats:styled-content> pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient‐sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. In response to environmental cues, this recently discovered lysosomal nutrient‐sensing complex regulates autophagy transcriptionally through conserved factors, such as the transcription factors <jats:styled-content style="fixed-case">TFEB</jats:styled-content> and <jats:styled-content style="fixed-case">FOXO</jats:styled-content>, associated with lifespan extension. This key metabolic pathway strongly depends on nucleocytoplasmic compartmentalization, a cellular phenomenon gradually lost during aging. In this review, we discuss the current progress in understanding the contribution of <jats:styled-content style="fixed-case">mTOR</jats:styled-content>‐regulating factors to autophagy and longevity. Furthermore, we review research on the regulation of metabolism conducted in multiple aging models, including <jats:italic>Caenorhabditis elegans</jats:italic>,<jats:italic> Drosophila</jats:italic> and mouse, and human <jats:styled-content style="fixed-case">iPSC</jats:styled-content>s. We suggest that conserved molecular pathways have the strongest potential for the development of new avenues for treatment of age‐related diseases.</jats:p>