Aging is the process of physiological deterioration over time. One of the hallmarks of aging is a failure in the maintenance of protein homeostasis, including protein homeostasis in the ER (Endoplasmic Reticulum). Accordingly, accumulation of misfolded proteins in the ER and aggregate formation are both associated with many age-related diseases. To identify new ways to ameliorate ER stress resistance, our lab conducted a forward genetic screen in C. elegans for mutations that confer resistance to the ER stress inducer tunicamycin. The screen revealed many mutations associated with defective sensory cilia structure/function. We find that the extreme ER stress resistance of these animals is complex as it is attributed by at least three combined pathways: a daf-16 dependent pathway, an IRE-1 UPR pathway and additional pathway/pathways whose identity is still unknown. Altogether, these findings indicate that animals with an impaired sensory system activate a variety of defense mechanisms that provide global stress resistance.