Pathology of Mouse Models of Accelerated Aging

Abstract

Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data.

Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice

“…After reaching adulthood, the senescence and SASP markers were significantly increased in multiple tissues and by multiple measures, and continued to rise as the animals aged (Figures and ). This correlates with the onset and progression of age‐related pathologies in multiple tissues of the Ercc1 − /∆ model (Dolle et al, ; Gregg et al, ; Gurkar & Niedernhofer, ; Harkema et al, ; Yousefzadeh et al, ; Yousefzadeh, Zhu, et al, ), providing further evidence that senescent cells play a causal role in numerous age‐related pathologies (Baker et al, ).…”

Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging

“…During GCV treatment, visual inspection of mice revealed obvious signs of aging such as pronounced spinal kyphosis and hair graying (Harkema, Youssef, & Bruin, 2016). We evaluated these parameters at the end of the treatment and found a significantly higher proportion of animals showing kyphosis in the Sox2‐TK treated group compared to the Sox2‐WT group (Figure 1c).…”

Vascular senescence and ageing: a role for the MEOX proteins in promoting endothelial dysfunction

“…In addition to the aforementioned mouse models, there exists several other genetically modified mouse strains that have shown potential utility for the study of vascular disease and ageing (Harkema et al 2016;Koks et al 2016). While the relatively short lifespan of mice permits the study of ageing, unlike humans, mice have much longer telomeres and do not have a propensity for the development of atherosclerotic vascular disease (Calado and Dumitriu 2013;Russell and Proctor 2006).…”