The endoplasmic reticulum (ER) is a multifunctional organelle which co-ordinates protein folding, lipid biosynthesis, calcium storage and release. Perturbations that disrupt ER homeostasis lead to ER stress and upregulation of a signaling pathway called the unfolded protein response (UPR). The UPR while robust in young animals appears to be compromised with aging; many of the components of the UPR have decreased expression and activity with age. There is also considerable evidence of oxidative damage. There are suggestions that an impaired UPR may contribute to the acceleration of neurodegenerative disorders.