Research Description As an organism ages, its proteins face an increasing severity in the challenges they receive from extrinsic and intrinsic environmental perturbation. Chaperones become dysregulated, while the degradation machineries stop working properly. The protein accumulates damage and starts to misfold. At this point, the cell needs to mount a response to restore its homeostasis; however, the stress response machinery that it typically relies upon when faced with such challenges has lost its capacity to function. This breakdown, however, does not lead to complete disorder. As the organism ages, it exhibits a degree of correlated, recognizable, and predictable changes to its physiology over time. These changes can occur synchronously across multiple tissues and organs. The phenotypic changes of aging occur in a type of concert, rather than in isolation, suggesting the residual participation of the endocrine system in the onset of age-related phenotypes. The demise of the cell thus most often occurs within the context of the simultaneous demise of the whole organism.