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A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner.

ABSTRACT: A frailty index (FI) based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores, and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 and 23 months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool. Interestingly, while FI-Clinical scores were higher in females, the opposite was true for FI-Lab scores and there was no sex difference in FI-Combined scores. All three FI tools revealed a positive correlation between pro-inflammatory cytokine levels and frailty in aging mice that differed between the sexes. Elevated levels of the pro-inflammatory cytokines interleukin (IL)-6, IL-9, and interferon-? were associated with higher FI scores in aging females, while levels of IL-12p40 rose as FI scores increased in older males. Thus, an FI tool based on common laboratory tests can quantify frailty in mice; the positive correlation between inflammation and frailty scores in naturally aging mice differs between the sexes.

SUBMITTER: Kane AE

PROVIDER: S-EPMC6376103 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner.

Kane Alice E AE Keller Kaitlyn M KM Heinze-Milne Stefan S Grandy Scott A SA Howlett Susan E SE

The journals of gerontology. Series A, Biological sciences and medical sciences 20190201 3

A frailty index (FI) based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores, and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 and 23 months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) ba ...[more]

PMID: 29788087

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Project description:To explore the association between a newly developed cumulative laboratory-based frailty index (FI) and intrinsic (personal) and extrinsic (social, environmental) characteristics.Cross-sectional longitudinal study.The third and fourth waves of the community-representative, five-county, 10-year Duke Established Populations for Epidemiologic Studies of the Elderly study, carried out in a health service-rich area.Cognitively intact survivors of the third wave (N = 1,740), who provided blood samples for standard laboratory work.Biomarkers (n = 28) were measured to develop a cumulative deficit laboratory test-based FI (Duke FI) derived from standard laboratory tests: SMAC-24 chemistry panel, high-density lipoprotein cholesterol panel, and complete blood count. Information was gathered on scales assessing intrinsic characteristics (personal locus of control, life satisfaction, self-esteem, depressive symptomatology) and extrinsic characteristics (support received from and provided to family and friends, stressful life events, neighborhood disadvantage).The newly developed Duke FI had content, construct, concurrent, and predictive validity. In addition to sex, race, and income, the Duke FI was associated at the intrinsic level with locus of control, self-esteem, life satisfaction, and depressive symptomatology (each P < .01) and at the extrinsic level with provision (P < .01) and with receipt of instrumental help (P < .10), social stressors (P < .03), and neighborhood disadvantage (P < .01) in unadjusted analysis; race fully explained neighborhood disadvantage.Intrinsic (personality) characteristics and personally close extrinsic characteristics (contacts with family and friends, personal stressors) are associated with laboratory test-based frailty, as is neighborhood disadvantage, although in this accessible, health service-rich environment, race fully explained association with neighborhood disadvantage, suggesting that interventions to reduce frailty in residents in such an environment should pay particular attention to characteristics that immediately affect the individual.

Project description:BackgroundFrailty has been associated with a decline in sensory and motor function. However, given that different frailty measures were shown to overlap but also differ in their diagnostic properties, sensory and motor correlates of frailty might be different depending on the operationalization of frailty. Our objective was to identify sensory and motor determinants of frailty and compare the results between frailty phenotype (FP) and frailty index (FI).MethodsData from 44 pre-frail and frail subjects aged 65 and above were used. Frailty was measured using the FP and the FI. Sensory function in the visual, auditory, and tactile domain was assessed using visual acuity, absolute hearing threshold and mechanical detection threshold. Upper extremity motor performance was evaluated by the Purdue Pegboard Test and the Short Physical Performance Battery was used to assess lower extremity motor function. Multiple logistic regression models were employed to determine associations of sensory and motor function with frailty vs. pre-frailty for both frailty measures.ResultsThe frailty measures were moderately correlated (0.497, p ≤ 0.01) and had a Kappa agreement of 0.467 (p = 0.002). Using the FP, frailty was significantly associated with reduced upper extremity motor function only (OR = 0.50, 95% CI 0.29-0.87, p = 0.014). Frailty as assessed by the FI was significantly related to higher hearing thresholds (OR = 1.21, 95% CI 1.02-1.43, p = 0.027) and reduced lower extremity performance (OR = 0.32, 95% CI 0.13-0.77, p = 0.012).ConclusionFrailty is related to reduced performance in measures of sensory and motor function. However, traditional measures of frailty might be differentially sensitive to capture sensory and motor decline, possibly contributing to the much-observed discordance between the diagnostic instruments. This should be taken into account by researchers and clinicians when planning and evaluating therapeutic interventions for frailty.Trial registrationClinicalTrials.gov NCT03666039 . Registered 11 September 2018 - Retrospectively registered.

Project description:BackgroundFew studies have made longitudinal comparisons between frailty phenotype (FP) and frailty index (FI) changes. We aimed to investigate frailty status changes defined by FP and FI concurrently, and to compare the associated factors and incident disability among different combination of FI and FP trajectory groups.MethodsData on respondents aged over 50 who completed the 1999, 2003 and 2007 Taiwan Longitudinal Study on Aging (TLSA) surveys (n = 2807) were excerpted. Changes of FI, FP and major time-dependent variables were constructed by group-based trajectory modeling. Logistic regression was used to investigate the associated factors and relationships with incident disability among different frailty trajectories.ResultsWe identified four FP trajectories - stably robust, worsened frailty, improved frailty, and stably frail and three FI trajectories - stable FI, moderate increase FI and rapid increase FI. Lower self-rated health, mobility impairment, and depressed mood were associated with unfavorable FP and FI changes (all p < 0.001). Regardless of FP trajectory groups, the moderate and rapid increase FI group had significantly more comorbidities than the stable FI group, and more visual, hearing, oral intake impairment, more difficulty in meeting living expenses, and poorer cognitive function in ≥65-year-olds (all p < 0.05). In addition, the worsened frailty, improved frailty, and stably frail groups had ORs for incident disability of 10.5, 3.0, and 13.4, respectively, compared with the stably robust group (all p < 0.01); the moderate and rapid increase FI groups had 8.4-fold and 77.5-fold higher risk than the stable FI group (both p < 0.001). When combining FI and FP trajectories, risk increased with FI trajectory steepness, independent of FP change (all p < 0.01 in rapid increase FI vs stable FI).ConclusionsFour FP trajectories (stably robust, worsened frailty, improved frailty, and stably frail) and three FI trajectories (stable FI, moderate increase FI and rapid increase FI) were identified. Lower self-rated health, mobility impairment, and depressed mood were associated with both unfavorable FP and FI trajectories. Nevertheless, even for individuals in stably robust or improved frailty FP groups, moderate or rapid increase in FI, either due to comorbidities, sensory impairment, cognitive deficits, or financial challenges, may still increase the risk of incident disability.

Project description:BackgroundPrevious studies have shown that the frailty index based on laboratory tests (FI-Lab) can identify older adults at increased risk of adverse health outcomes. This study aimed to determine whether the FI-Lab is associated with mortality risk and can provide incremental improvements in risk stratification of patients with critical acute myocardial infarction (AMI).Materials and methodsWe conducted a secondary analysis of data from the Medical Information Mart for Intensive Care (MIMIC)-IV database. A 33-item FI-Lab was constructed. Outcomes of interest were in-hospital and 1-year mortality. Logistic regression models were used to investigate the association between the FI-Lab and outcomes. For the assessment of the incremental predictive value, the FI-Lab was added to several risk stratification scoring systems for critically ill patients, and the following indices were calculated: Δ C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).ResultsOut of 2,159 patients, 477 died in hospital (22.1%), and 898 died during the 1-year follow-up period. After adjustment for confounders, the FI-Lab was associated with increased in-hospital mortality [odds ratio (OR) = 1.06, 95% confidence interval (CI): 1.05-1.07] and 1-year mortality (OR = 1.05, 95% CI: 1.04-1.06) when assessed as a continuous variable (per 0.01-score increase). When assessed as a categorical variable, the FI-Lab was associated with in-hospital mortality (2nd Quartile: OR = 1.89, 95% CI: 1.18-3.03; 3rd Quartile: OR = 3.46, 95% CI: 2.20-5.46; and 4th Quartile: OR = 5.79, 95% CI: 3.61-9.28 compared to 1st Quartile) as well as 1-year mortality (2nd Quartile: OR = 1.66, 95% CI: 1.23-2.24; 3rd Quartile: OR = 2.40, 95% CI: 1.76-3.26; and 4th Quartile: OR = 3.76, 95% CI: 2.66-5.30 compared to 1st Quartile) after adjustment for confounders. The addition of the FI-Lab to all disease severity scores improved discrimination and significantly reclassified in-hospital and 1-year mortality risk.ConclusionThe FI-Lab was a strong predictor of short- and long-term mortality in patients with critical AMI. The FI-Lab improved the ability to predict mortality in patients with critical AMI and therefore might be useful in the clinical decision-making process.

Project description:C-cyanomethanimine (HNCHCN), existing in the two Z and E isomeric forms, is a key prebiotic molecule, but, so far, only the E isomer has been detected toward the massive star-forming region. Sagittarius B2(N) using transitions in the radio wavelength domain.With the aim of detecting HNCHCN in Sun-like-star forming regions, the laboratory investigation of its rotational spectrum has been extended to the millimeter-/submillimeter-wave (mm-/submm-) spectral window in which several unbiased spectral surveys have been already carried out.High-resolution laboratory measurements of the rotational spectrum of C-cyanomethanimine were carried out in the 100-420 GHz range using a frequency-modulation absorption spectrometer. We then searched for the C-cyanomethanimine spectral features in the mm-wave range using the high-sensitivity and unbiased spectral surveys obtained with the IRAM 30-m antenna in the ASAI context, the earliest stages of star formation from starless to evolved Class I objects being sampled.For both the Z and E isomers, the spectroscopic work has led to an improved and extended knowledge of the spectroscopic parameters, thus providing accurate predictions of the rotational signatures up to ~700 GHz. So far, no C-cyanomethanimine emission has been detected toward the ASAI targets, and upper limits of the column density of ~ 1011-1012 cm-2 could only be derived. Consequently, the C-cyanomethanimine abundances have to be less than a few 10-10 for starless and hot-corinos. A less stringent constraint, ? 10-9, is obtained for shocks sites.The combination of the upper limits of the abundances of C-cyanomethanimine together with accurate laboratory frequencies up to ~ 700 GHz poses the basis for future higher sensitivity searches around Sun-like-star forming regions. For compact (typically less than 1?) and chemically enriched sources such as hot-corinos, the use of interferometers as NOEMA and ALMA in their extended configurations are clearly needed.

Dataset Information

A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner.

Publications

A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner.

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