Experimental Section / Mini-Review Gerontology Frailty Assessment in Animal Models Stefan D. Heinze-Milne a Shubham Banga a Susan E. Howlett a, b a Department of Pharmacology, Dalhousie University, Halifax, NS, Canada; b Department of Medicine (Geriatric Medicine), Dalhousie University, Halifax, NS, Canada Received: April 8, 2019 Accepted after revision: June 5, 2019 Published online: July 22, 2019 Susan E. Howlett, PhD Department of Pharmacology, Dalhousie University 5850 College St., PO Box 15000 Halifax, NS B3H 4R2 (Canada) E-Mail susan.howlett @dal.ca © 2019 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/ger DOI: 10.1159/000501333 Keywords Aging · Animal models · Frailty · Frailty index · Frailty phenotype · Health span Abstract Although frailty has been extensively investigated for the last 2 decades, preclinical models of frailty have only been developed over the past decade. Frailty is a concept that helps to explain the difference between chronologic age and biologic age and to discuss health span along with lifes- pan. In general, a frail individual will be more susceptible to adverse health outcomes than a healthy, nonfrail individual of the same age. However, the biology and mechanisms of frailty are still unclear. The development of preclinical mod- els of frailty and frailty assessment tools are invaluable to geriatric research. This review briefly describes the concept of frailty and discusses the newly developed animal models of frailty, specifically the frailty phenotype- and frailty index- based models. Mouse models are the most common models for preclinical frailty research, but rat and canine models for frailty assessment have also been developed. These models can facilitate the testing of frailty-specific treatments and help to investigate the effects of various interventions on frailty. Similarities and differences between human and ani- mal models, including sex differences in frailty, are also dis- cussed. The availability of animal models of frailty is a valu- able and welcome addition to the study of frailty, aging, or the disorders of old age and will enable a better understand- ing of frailty mechanisms. © 2019 S. Karger AG, Basel Introduction to Frailty How and why people “age” at different rates continues to elude us. It has long been known that people and ani- mals develop health deficits at different rates as they age. Some individuals simply become frail faster than others, although the reasons for this are not well understood and may involve several mechanisms. In recent years, the in- terest in understanding and quantifying frailty has grown. This is, in part, due to the aging population in many de- veloped countries. The prevalence of frail older people increases with age (i.e., >80 years) around the globe [1]. This is problematic for healthcare since frail individuals are at an increased risk of morbidity/mortality [2]. Frailty has no internationally accepted definition; however, it has been defined as an increased susceptibility to adverse health outcomes [3]. It is associated with age and disease, although neither is necessary for frailty to occur [4]. The biology of frailty is not yet well understood, although pro- posed mechanisms include increased oxidative stress, DNA repair malfunction, chronic inflammation, cellular senescence, endocrine dysfunction, and mitochondrial damage [4, 5]. Overall it is thought that frailty lowers physiologic reserves, which predisposes a frail person to a worse reaction to health challenges than a nonfrail per- son. Frailty has been studied in humans increasingly since the early 2000s. The breakthrough into studying frailty as a clinical condition was the development of tools to quan- tify frailty. The 2 dominant methods to measure frailty in