Oral health in geroscience: animal models and the aging oral cavity

Abstract

Age is the single greatest risk factor for many diseases, including oral diseases. Despite this, a majority of preclinical oral health research has not adequately considered the importance of aging in research aimed at the mechanistic understanding of oral disease. Here, we have attempted to provide insights from animal studies in the geroscience field and apply them in the context of oral health research. In particular, we discuss the relationship between the biology of aging and mechanisms of oral disease. We also present a framework for defining and utilizing age-appropriate rodents and present experimental design considerations, such as the number of age-points used and the importance of genetic background. While focused primarily on rodent models, alternative animal models that may be particularly useful for studies of oral health during aging, such as companion dogs and marmoset monkeys, are also discussed. We hope that such information will aid in the design of future preclinical studies of geriatric dental health, thus allowing more reliability for translation of such studies to age-associated oral disease in people.

Keywords: Dentistry; Dogs; Dry mouth; Hallmarks of aging; Inflammation; Marmosets; Mice; Oral cancer; Oral microbiome; Periodontal disease; Rapamycin; Xerostomia; mTOR.

Fig. 1

Periodontal disease is an age-associated disorder. The percentage of adults in USA with clinical periodontitis is shown for different age groups (mean, 24 teeth). Periodontitis is defined by a combination of periodontal probing depth and clinical attachment loss from six different sites per tooth on all teeth. All data were derived from the Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009–2012 (Eke et al., 2015 )

Fig. 2

Age-related oral diseases share molecular links with the hallmarks of aging. Highlighting a few oral health conditions in relationship to aging hallmarks (Bhattacharya & , R. Roy, A.M. Snijders, G. Hamilton, J. Paquette, T. Tokuyasu, H. Bengtsson, R.C.K. Jordan, A.B. Olshen, D. Pinkel, B.L. Schmidt, D.G. Albertson, ; Sumida & Hamakawa, ; Thevaranjan et al., ; Barrera et al., ; Khan et al., ; Yin & Chung, ; Parkinson et al., ; Lindroth & Park, ; Paul et al., ; Ballestar, 2011)

Fig. 3

Mouse age is an important consideration when modeling human age-associated disease. A typical survival curve for C57BL/6JNia mice maintained in the laboratory (adapted from 42). A mouse is mostly developmentally mature and can be considered a young adult by about 6 months of age. Most geroscience studies would not consider a mouse to be old until 18–24 months of age. A rough comparison of human age ranges is shown for different mouse ages. When studying or modeling a disease process that is most prevalent in elderly people, it is strongly recommended that older mice be used, in order to recapitulate the contributions of physiological changes that only occur in an aged animal