A Comparison of Two Mouse Frailty Assessment Tools.

The mouse clinical frailty index and the mouse frailty phenotype assessment are two recently developed tools used to assess frailty in mice. The objectives of this study were to investigate whether the same mice are identified as frail with both tools and to examine the association of each of the assessment tools with age and frailty-related outcomes. Frailty was measured using both tools in old (~24 months; n = 36) C57BL/6 male mice. After 2 weeks, blood pressure and heart rate were measured and serum samples were collected for analysis of alanine aminotransferase, creatinine, and albumin levels. The mouse frailty phenotype assessment identified no mice as frail but modification of the assessment tool identified six mice as frail. The mouse clinical frailty index identified 16 mice as frail and the agreement between the two scales was 50.0%. Increasing clinical frailty index scores were correlated with low serum alanine aminotransferase, as well as decreased heart rate, and reduced heart rate variance. We conclude that, consistent with equivalent frailty assessment scales in humans, both tools have value but do not necessarily identify the same mice as frail.

Kane AE ，Huizer-Pajkos A ，Mach J ，Mitchell SJ ，de Cabo R ，Le Couteur DG ，Howlett SE ，Hilmer SN ... -  《-》

Development of a Rat Clinical Frailty Index.

Rats are a commonly used model for aging studies, and a frailty assessment tool for rats would be of considerable value. There has been a recent focus on the development of preclinical models of frailty in mice. A mouse clinical frailty index (FI) was developed based on clinical frailty assessment tools. This FI measures the accumulation of clinically evident health-related deficits in mice. This paper aimed to develop a rat clinical FI. Male Fischer 344 rats were aged from 6 to 9 months (n = 12), and from 13 to 21 months (n = 41). A FI comprised of 27 health-related deficits was developed from a review of the literature and consultation with a veterinarian. Deficits were scored 0 if absent, 0.5 if mild, or 1 if severe. A FI score was determined for each rat every 3-4 months, and for the older group mortality was assessed up to 21 months. Mean FI scores significantly increased at each time point for the older rats. A high FI score measured at both 17 months of age and terminally was also associated with decreased probability of survival as assessed with Kaplan-Meier curves. The rat clinical FI has significant value for use in aging and interventional studies.

Yorke A ，Kane AE ，Hancock Friesen CL ，Howlett SE ，O'Blenes S ... -  《-》

A Clinically Relevant Frailty Index for Aging Rats.

Frailty is a clinical syndrome that is increasingly prevalent during aging. Frailty involves the confluence of reduced strength, speed, physical activity, and endurance and is associated with adverse health outcomes. The present study adapts existing clinical and preclinical indices of frailty to the Fischer (F344) rat. Male F344 rats (n = 133; 17 mo) completed a battery of behavioral tasks, including forelimb wire suspension (strength), rotarod (speed), open field (physical activity), and inclined screen (endurance). Rats that performed poorly (lowest quintile) on two tasks were considered mildly frail (17.29%, n = 23), and rats that performed poorly on 3-4 tasks were considered frail (2.26%, n = 3). Logistic regression of 100-day survival revealed that mildly frail rats were 3.8 times and frail rats were 27.5 times more likely to die during that period than nonfrail rats (p = .038; 95% confidence interval: 2.030, 372.564). The selected criterion tests, cutoff points, and index provide a potential tool for identifying frailty in aged F344 rats, which is consistent with existing frailty indices for humans and mice.

Miller MG ，Thangthaeng N ，Shukitt-Hale B 《-》

Comparison of frailty indicators based on clinical phenotype and the multiple deficit approach in predicting mortality and physical limitation.

To compare three simple bedside tools based on frailty phenotypes with a Frailty Index using the multiple deficit approach in the prediction of mortality and physical limitation after 4 years. Cohort study. Hong Kong, China. Four thousand men and women aged 65 and older living in the community who were ambulatory enough to attend the study center. Interviewers obtained information regarding physical, psychological, and functional health; body mass index (BMI), grip strength, blood pressure, and ankle brachial index were determined. Three clinical frailty scales based on the Fried phenotype (Cardiovascular Health Study (CHS); Fatigue, Resistance, Ambulation, Illness, and Loss (FRAIL); and Hubbard) and a frailty index (FI) were constructed from these variables, and their ability to predict incident mortality and physical function limitations was compared using receiver operating characteristic (ROC) curves. All tools predicted adverse outcomes. More participants were categorized into frail and prefrail categories using the CHS than with the other two clinical scales. For all frailty measures, with increasing levels of frailty, the sensitivity fell and the specificity increased to greater than 90%; the area under the ROC curve values were approximately 0.6. Simple frailty scores are comparable with a multidimensional deficit accumulation FI in predicting mortality and physical limitations. The newer FRAIL, proposed for use in a clinical setting, is comparable with other existing short screening tools, as well as tools based on the multiple-deficits model used for research settings. Addition of a physical performance measure to screening tools may increase predictive accuracy.

Woo J ，Leung J ，Morley JE 《-》

A New Frailty Score for Experimental Animals Based on the Clinical Phenotype: Inactivity as a Model of Frailty.

The development of animal models to study human frailty is important to test interventions to be translated to the clinical practice. The aim of this work was to develop a score for frailty in experimental animals based in the human frailty phenotype. We also tested the effect of physical inactivity in the development of frailty as determined by our score. Male C57Bl/6J mice, individually caged, were randomly assigned to one of two groups: sedentary (inactive) or spontaneous wheel-runners. We compared the sedentary versus the active lifestyle in terms of frailty by evaluating the clinical criteria used in humans: unintentional weight loss; poor endurance (running time); slowness (running speed); weakness (grip strength), and low activity level (motor coordination) at five different ages: 17, 20, 23, 26 and 28 months of age. Each criterion had a designated cut-off point to identify the mice with the lowest performance. Lifelong spontaneous exercise significantly retards frailty. On the contrary sedentary animals become frail as they age. Thus, physical inactivity is a model of frailty in experimental animals. Our frailty score provides a tool to evaluate interventions in mice prior to translating them to clinical practice.

Gomez-Cabrera MC ，Garcia-Valles R ，Rodriguez-Mañas L ，Garcia-Garcia FJ ，Olaso-Gonzalez G ，Salvador-Pascual A ，Tarazona-Santabalbina FJ ，Viña J ... -  《-》