Frontiers in Bioscience · Oct 10, 2026
Targeting Endoplasmic Reticulum Stress as a Promising Strategy Against Aging
By Hu L, Li H, Abudurexiti D et al.
The endoplasmic reticulum (ER) is a vital organelle in eukaryotic cells that plays a key role in processes such as protein folding, post-translational modifications, and the regulation of intracellular calcium storage. Disruptions in ER function as organisms age can lead to endoplasmic reticulum stress (ERS), which activates the unfolded protein response (UPR). The UPR aims to restore ER homeostasis by modulating protein synthesis, facilitating the degradation of misfolded proteins and increasing the expression of molecular chaperones. However, sustained or severe ERS can trigger apoptosis, and has been associated with various age-related pathologies, such as neurodegenerative diseases, metabolic syndrome, and cardiovascular disorders. In this review, we systematically explore the pathophysiological mechanisms of ERS and the UPR, with a particular focus on structural and functional alterations during aging. Furthermore, we have summarized the significant roles of ERS and the UPR in various age-related diseases, review recent advances in anti-aging therapies targeting these pathways, and discuss potential future intervention strategies.