Physical resilience is the ability of an organism to respond to physical stress, and can be measured with various types of stress tests. The loss of resilience occurs earlier than the development of frailty. Thus, loss of resilience may result in age-related frailty. When measuring overall resilience, integrative responses involving multiple tissues, organs, and activities are desirable, so as to inform about the overall health status of the animal. Therefore, it is more likely that a battery of stress tests, rather than a single all-encompassing one, will be more informative. An ideal battery of tests should have enough dynamic range in the response to allow characterization of an individual in easily distinguishable groups as being resilient or non-resilient. Based on features of duplication as well as translational relevance, we have selected a number of stressors to investigate including the chemotherapeutic drug cyclophosphamide, sleep deprivation, wheel running, high fat diet, and pneumococcal vaccine. All stressors have quantifiable readouts, and we are showing that an age-dependent response of each individual stressor aligns with systemic physiological and geropathological measurements. For example, the neutrophil rebound response to cyclophosphamide decreases with increasing age, and young high-responder mice have better physiological performance and less disease at middle age than young low-responder mice. We are finding similar profiles for the other stressors, and will soon begin panel testing to determine if a battery approach provides a more robust prediction of resilience to aging in mice. We also are investigating the ability of individual stressors to measure resilience as an endpoint to anti-aging drugs. These preclinical mouse studies are aimed at development of resilience as a translational aging signature to not only predict healthy aging, but validate drug responses in middle age and geriatric populations.