Experimental design for mouse aging studies has historically involved lifespan, but it is now clear that survival data without pathologic data limis the information that can be obtained on aging animals. This limitation becomes more serious when interventions of any sort are implemented. Pathology gives an insight into the health of an animal by revealing lesions not readily observable in the live animal. As such, it is a snapshot of disease conditions at the time of death. Therefore, the long term goal is to establish pathologic information as an essential component of studies involving aging animals. Given that pathologic assessment is essential to help define the progression of lesions associated with aging, the real challenge is including it in aging studies because there is currently a lack of specialized expertise and resources. The objective of this application is to increase the level and scope of pathologic assessment of tissues from old mice involved in aging studies using a core network of pathologists and scientists with expertise in the pathology of aging. The rationale for the proposed work is that the expertise and methods for assessing aging pathology are critically lacking and as such impose major limitations on gathering essential information from aging studies. We plan to attain the objective of this application by pursuing two specific aims.
Aim 1 i designed to provide an environment to promote learning and exchange of scientific information for pathologists and other scientists in aging pathology research through a series of pathology of aging online research symposia. The symposia will also be a venue for presenting updates on progress on the development of uniform ways of integrating pathology into aging studies of mice as described in Aim 2.
Aim 2 will focus on the correlation of pathology data with longitudinal and cross-sectional lifespan data and physiologic data by enhancing standard histologic assessment of lesions observed in tissues from old mice. There will be one-week hands- on training sessions for selected individual trainees. The approach is innovative because it is based on the concept that pathologic assessment can be promoted by a series of online research symposia conducted by expert pathologists and scientists with a focus on new information and exchange of scientific ideas related to pathology of aging. The proposal is significant because it will provide an environment for the development and integration of pathology data into aging studies of mice, encourage more pathologists and other scientists to specialize in pathology of aging, and establish relevant standards to compare with other species including humans. Such results would be expected to have an important positive impact on aging studies because of the significant empowerment on data analyses and interpretation.
The proposed research is relevant to public health because it will enhance the importance and use of pathologic information as an essential component of aging studies that will help determine effective prevention and treatment procedures. Thus the proposed project is relevant to the pad of NIH's mission that pertains to developing knowledge that will help to reduce the burden of human disability.
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| Niedernhofer, L J; Kirkland, J L; Ladiges, W (2017) Molecular pathology endpoints useful for aging studies. Ageing Res Rev 35:241-249 |
| Lefebvre, Kathi A; Kendrick, Preston S; Ladiges, Warren et al. (2017) Chronic low-level exposure to the common seafood toxin domoic acid causes cognitive deficits in mice. Harmful Algae 64:20-29 |
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| Ladiges, Warren (2016) Pathology assessment is necessary to validate translational endpoints in preclinical aging studies. Pathobiol Aging Age Relat Dis 6:31478 |
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