ABSTRACT
BACKGROUND: The ability to identify frail older adults using a self-reported version of the physical frailty phenotype (PFP) that has been validated with the standard PFP could facilitate physical frailty detection in clinical settings. METHODS: We collected data from volunteers (N = 182), ages 65 years and older, in an aging research registry in Baltimore, Maryland. Measurements included: standard PFP (walking speed, grip strength, weight loss, activity, exhaustion); and self-reported questions about walking and handgrip strength. We compared objectively-measured gait speed and grip strength to self-reported questions using Cohen's Kappa and diagnostic accuracy tests. We used these measures to compare the standard PFP with self-reported versions of the PFP, focusing on a dichotomized identification of frail versus pre- or non-frail participants. RESULTS: Self-reported slowness had fair-to-moderate agreement (Kappa(k) = 0.34-0.56) with measured slowness; self-reported and objective weakness had slight-to-borderline-fair agreement (k = 0.10-0.21). Combining three self-reported slowness questions had highest sensitivity (81%) and negative predictive value (NPV; 91%). For weakness, three questions combined had highest sensitivity (72%), while all combinations had comparable NPV. Follow-up questions on level of difficulty led to minimal changes in agreement and decreased sensitivity. Substituting subjective for objective measures in our PFP model dichotomized by frail versus non/pre-frail, we found substantial (k = 0.76-0.78) agreement between standard and self-reported PFPs. We found highest sensitivity (86.4%) and NPV (98.7%) when comparing the dichotomized standard PFP to a self-reported version combining all slowness and weakness questions. Substitutions in a three-level model (frail, vs pre-frail, vs. non-frail) resulted in fair-to-moderate agreement (k = 0.33-0.50) with the standard PFP. CONCLUSIONS: Our results show potential utility as well as challenges of using certain self-reported questions in a modified frailty phenotype. A self-reported PFP with high agreement to the standard phenotype could be a valuable frailty screening assessment in clinical settings.
Subject(s)
Frailty , Aged , Cross-Sectional Studies , Frail Elderly , Frailty/diagnosis , Frailty/epidemiology , Geriatric Assessment/methods , Hand Strength , Humans , Independent Living , Registries , Self ReportABSTRACT
Chronic inflammation (CI) in older adults is associated with reduced health span and life span. Interleukin-6 (IL-6) is one CI marker that is strongly associated with adverse health outcomes and mortality in aging. We have previously characterized a mouse model of frailty and chronic inflammatory pathway activation (IL-10tm/tm, IL-10 KO) that demonstrates the upregulation of numerous proinflammatory cytokines, including IL-6. We sought to identify a more specific role for IL-6 within the context of CI and aging and developed a mouse with targeted deletion of both IL-10 and IL-6 (IL-10tm/tm/IL-6tm/tm, DKO). Phenotypic characteristics, cytokine measurements, cardiac myocardial oxygen consumption, physical function, and survival were measured in DKO mice and compared to age- and gender-matched IL-10 KO and wild-type mice. Our findings demonstrate that selective knockdown of IL-6 in a frail mouse with CI resulted in the reversal of some of the CI-associated changes. We observed increased protective mitochondrial-associated lipid metabolites, decreased cardiac oxaloacetic acid, improved myocardial oxidative metabolism, and better short-term functional performance in DKO mice. However, the DKO mice also demonstrated higher mortality. This work shows the pleiotropic effects of IL-6 on aging and frailty.
Subject(s)
Aging/physiology , Inflammation/physiopathology , Interleukin-6/deficiency , Aging/genetics , Animals , Chronic Disease , Citric Acid Cycle , Disease Models, Animal , Female , Glycolysis , Inflammation/genetics , Interleukin-10/deficiency , Interleukin-10/genetics , Interleukin-10/physiology , Interleukin-6/genetics , Interleukin-6/physiology , Lipids/blood , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria, Heart/metabolism , Oxidative PhosphorylationABSTRACT
Interleukin 10tm1Cgn (IL 10tm) mice have been utilized as a model of chronic inflammation and declining health span because of their propensity to develop chronic activation in NFkB pathways, skeletal muscle and cardiac changes, and mitochondrial dysfunction. We hypothesized that older IL 10tm frail mice would have alterations similar to frail, older humans in measured parameters of glucose metabolism, oxygen consumption (VO2), respiratory quotient (RQ), spontaneous locomotor activity, body composition and plasma adipokine levels. To test this hypothesis, we investigated these metabolic parameters in cohorts of 3, 10, and 20 month old IL 10tm female mice and age and gender matched C57Bl/6 mice. Insulin sensitivity, glucose homeostasis, locomotor activity and RQ were not significantly altered between the two strains of mice. Interestingly, old IL 10tm mice had significantly decreased VO2 when normalized by lean mass, but not when normalized by fat mass or the lean/fat mass ratio. NMR based body composition analysis and dissection weights show that fat mass is decreased with age in IL 10tm mice compared to controls. Further, plasma adiponectin and leptin were also decreased in IL 10tm.These findings suggest that frailty observed in this mouse model of chronic inflammation may in part be driven by alterations in fat mass, hormone secretion and energy metabolism.