Pathology increases exponentially with age. Therefore, to determine if an intervention has effects on aging, longevity, and healthspan, investigators must know how the intervention affects age-related pathological lesions. Furthermore, pathological assessment of old animals helps investigators determine whether changes (functional, biochemical, molecular, etc.) are associated with, or independent of, underlying pathological conditions and histological changes. Such assessments also provide insights into potential biological/molecular mechanism(s) of the intervention. In addition, pathological analysis of young animals can reveal how genetic, pharmacological, and other interventions affect early life development. Thus, it is essential to obtain accurate and thorough histopathological assessments of animals throughout the lifespan. During the current funding period, the SA Shock Center Pathology Core performed services for 50 investigators (35 external to UTHSCSA). The resultant data were used in 26 publications (including papers in Cell, Cell Metabolism, Nature Cell Biology, Nature Communication, and Nature Medicine). With the rapid expansion of aging biology research locally and across the country, we anticipate that the demand for Pathology Core services will grow even more. The Pathology Core will provide investigators with detailed pathological analyses of age-related lesions in mice, rats, and other animal models, e.g., non-human primates. The Core will also offer histopathological, morphometric, immunohistochemical and molecular analyses of specific lesions and tissues. These include neoplastic lesions, inflammation, senescent cells, glomerulonephritis, brain gliosis, and histological characteristics of adipose tissue. The Specific Aims of the Core are: 1. To conduct comprehensive end-of-life and cross-sectional pathological analyses of established and new rodent models and other species used in aging research (including non-human primates). 2. To conduct immunohistochemical, molecular and quantitative morphometric analyses of tissues/organs of rodent models and other species to better understand age-related histological changes. 3. To continue to: a) amass a comprehensive database of histopathological data and images as a resource for the scientific community; b) provide basic pathological information for new studies; and c) create a tissue archive as a resource for morphological, biochemical and molecular analyses. 4. To provide histopathology services for investigators by preparing paraffin and frozen blocks, making unstained slides, and performing special staining. Histology services also include: a) preparation of tissue array slides for histological/morphological experiments; and b) performing laser capture microdissection. 5. To assist faculty and trainees with the interpretation of data from pathological analyses in models of aging and help them with their grant applications and manuscripts.