Physical Resilience

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 much 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, 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. We have selected four stressors, cold, sleep deprivation, isoflurane anesthetic exposure, and the chemotherapeutic drug cyclophosphamide, to investigate based on features of duplication as well as translational relevance. The hypothesis of this proposal is that a physical stress test panel consisting of 3 stressors (cold, sleep deprivation, isoflurane exposure, or cyclophosphamide) will measure resilience and predict healthy aging in mice.

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Aging Intervention – Alzheimers Disease

We hypothesize that preventing or reversing the decline in mitochondrial function during aging will be effective in preventing or reversing cognitive decline and pathologic processes associated with Alzheimers Disease (AD). We will test our hypothesis by inducing Aβ42 pathology and human mutant Tau (P301L) pathology in the hippocampus of aged mice (ADAβ42 and AD Tau mice), and then treating these mice with SS-31 or saline.