Pathology is a critical aspect of preclinical aging studies

Abstract

Experimental design for mouse aging studies has historically involved lifespan, but it is now clear that survival data without pathology data limit 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, a long-term goal is to establish pathology information as an essential component of studies involving health span and lifespan of aging animals. Given that pathology 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. An increase in the level and scope of pathology assessment of tissues from old mice involved in aging studies is needed. A focus on the correlation of pathology data with longitudinal and cross-sectional lifespan data and health span physiology data can be established by enhancing standard histologic assessment of lesions observed in tissues from old mice. An environment for the development and integration of pathology data into aging studies of mice is needed to 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 will have an important positive impact on aging studies because of the significant empowerment on data analyses and interpretation.

The Vital Role of Pathology in Improving Reproducibility and Translational Relevance of Aging Studies in Rodents

“…2,3 The lack of standardized, well planned, and well-executed pathology assays in long-term and resource-intensive aging studies is problematic and should be addressed by developing and adopting consistent pathology protocols, terminology, and scoring systems. 41,42 Systematically employed, consistently applied pathology end points will increase accuracy, reproducibility, and translatability of preclinical interventional aging studies. 13,22 …”

“…This is for financial and logistical reasons as well as a perceived lack of access to expertise or failure to realize that histopathology contributes meaningfully to an understanding of treatment intervention effects. 2,41,64,65 The powerful multi-disciplinary datasets generated in preclinical testing are obtained through in-life and terminal metrics, consensus terminology and diagnostic criteria, lesion scoring, and data management. 32,33,64,65 Protocols and experimental designs should be standardized and well described.…”

“…Aging studies should strive to document all lesions present within an individual as it is the total burden of disease (or absence thereof) that defines health and enables investigations into senescence in non-diseased models. 11,19,41,59 Mechanisms of delayed aging or pathogenesis of altered disease onsets or total burden may be more fully characterized if a complete data set is generated and published. An aging population (human or rodent) typically has more than one independent disease process (co-morbidities) which may contribute to cause of death, although death may also be due to a single disease entity.…”

Histopathologic Evaluation and Scoring of Viral Lung Infection

“…Inclusion of experienced board-certified pathologists, who are specially trained to examine and interpret tissues changes, as part of the multidisciplinary team can greatly enhance the quality of tissue evaluation [22,27]. By histopathology, a skilled eye (ideally a pathologist familiar with the model) can not only define the types of inflammatory processes, but also corroborate these findings to clinical signs and/or data from other analyses [22,[27][28][29][30]. In addition, pathologists have knowledge of correct lesion nomenclature, as well as potential effects of such variables as strainrelated background lesions, husbandry, the microbiome, and diet on the interpretation of results [25].…”

Principles and approaches for reproducible scoring of tissue stains in research

“…Tissue examination (histopathology) retains an important role in the diagnosis of clinical disease and evaluation of tissues in the research setting [1][2][3][4][5]. Examination and interpretation of tissue changes can be enhanced through labeling of cellular and tissue markers to identify features not observable by routine stains, such as specific cell types, activation states, and protein expression, to name a few.…”