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OBJECTIVES: To compare a composite measure of physical function that comprises locomotor and non-locomotor tests (i.e., the Mobility Battery Assessment (MBA)) with traditional measures of mobility (4-m usual gait speed (UGS), six-minute walk (6MW) gait speed, and short physical performance battery (SPPB) score) for assessing lower extremity function and discriminating community dwelling older adults with and without mobility limitations. DESIGN: Cross-sectional, observational study. SETTING: Laboratory-based. PARTICIPANTS: 89 community-dwelling older adults (74.9±6.7). MEASUREMENTS: Using principal component analysis we derived an MBA score for 89 community-dwelling older adults, and quantified 4-m UGS, 6MW gait speed, and SPPB score. The MBA score was based on five lab-based tests. We also quantified self-reported lower extremity function/mobility using the Neuro-QOL Lower Extremity Function-Mobility instrument. Based on this data a continuous score was derived and subjects were classified as “mobility limited” or “non-mobility limited”. Correlations between the mobility measures and the Neuro-QOL score were calculated, and ROC curves were constructed to determine the AUC for the mobility measures ability to predict mobility limitations. RESULTS: The MBA had the largest AUC (0.92) for discriminating mobility limitations and exhibited the strongest correlation (0.73) with the Neuro-QOL Lower Extremity Function-Mobility Scale. The worst performing predictors were the 4-meter UGS and stair climb power both with an AUC of 0.8 for discriminating mobility limitations, and a low correlation with Neuro-QOL Lower Extremity Function Scale of 0.39 and 0.46, respectively. CONCLUSION: The MBA score moderately improves the magnitude of correlation and discrimination of mobility limitation in older adults than singular, standard tests of mobility.

Background Approximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks. Methods In community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r2) for indices of lean mass, indices of muscle strength, and the four square step test. Results When aggregated by sex, the four square step test explained 17–34% of the variance for all mobility tasks (p p Conclusion The four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance. Trial registration NCT02505529–2015/07/22.

Sufficient physical activity (PA) reduces the risk of a myriad of diseases and preserves physical capabilities in later life. While there have been significant achievements in mapping accelerations to real-life movements using machine learning (ML), errors continue to be common, particularly for wrist-worn devices. It remains unknown whether ML models are robust for estimating age-related loss of physical function. In this study, we evaluated the performance of ML models (XGBoost and LASSO) to estimate the hallmark measures of PA in low physical performance (LPP) and high physical performance (HPP) groups. Our models were built to recognize PA types and intensities, identify each individual activity, and estimate energy expenditure (EE) using wrist-worn accelerometer data (33 activities per participant) from a large sample of participants (n = 247, 57% females, aged 60+ years). Results indicated that the ML models were accurate in recognizing PA by type and intensity while also estimating EE accurately. However, the models built to recognize individual activities were less robust. Across all tasks, XGBoost outperformed LASSO. XGBoost obtained F1-Scores for sedentary (0.932 ± 0.005), locomotion (0.946 ± 0.003), lifestyle (0.927 ± 0.006), and strength flexibility exercise (0.915 ± 0.017) activity type recognition tasks. The F1-Scores for recognizing low, light, and moderate activity intensity were (0.932±0.005), (0.840 ± 0.004), and (0.869 ± 0.005), respectively. The root mean square error for EE estimation was 0.836 ± 0.059 METs. There was no evidence showing that splitting the participants into the LPP and HPP groups improved the models’ performance on estimating the hallmark measures of physical activities. In conclusion, using features derived from wrist-worn accelerometer data, machine learning models can accurately recognize PA types and intensities and estimate EE for older adults with high and low physical function.

Objectives Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study. Design Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years. Setting LIFE was a multicenter eight-site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD. Participants Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment. Measurements Self-reported fatigue was assessed using the modified trait version of the Exercise-Induced Feelings Inventory, a six-question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual-paced 400-m walk every 6 months. We defined incident MMD as the inability to walk 400-m at follow-up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates. Results Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio [HR] for MMD = .71; 95% confidence interval [CI] = .57-.90; P = .004) and PMMD (HR = .60; 95% CI = .44-.82; P = .001). For those with lower baseline fatigue, no group differences in MMD (P = .36) or PMMD (P = .82) were found. Results of baseline fatigue by intervention interaction was MMD (P = .18) and PMMD (P = .05). Conclusion A long-term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619-624, 2020.

Background Cut-points to define slow walking speed have largely been derived from expert opinion. Methods Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4–6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not. Results Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as “fast”; 478 (9.5%) as “intermediate” (walking speed ≥0.62 m/s but Conclusions Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.

OBJECTIVES Decline in physical function is associated with older age. Healthcare utilization and expenditures related to physical functioning declines will likely increase as the proportion of the population of older adults rises. This study evaluated resource utilization associated with differences in physical functioning in a nationally representative sample of older adults. DESIGN A retrospective panel study nationally representative for 26 809 552 older adults in the United States. SETTING Medical Expenditure Panel Survey (MEPS) data from 2013 to 2014. PARTICIPANTS Adults aged 70 years or older who completed both rounds of the Self-Administered Questionnaire in MEPS. MEASUREMENTS Physical Component Score (PCS) from the Short-Form Health Survey as a measure of physical functioning was stratified into quartiles. Healthcare utilization (count of medical visits by setting) and total expenditures were assessed during and after the PCS measurements. Generalized linear mixed models, adjusted for demographic and clinical covariates, estimated the relationship between healthcare utilization and physical functioning. RESULTS The lowest functional status (Q1) was associated with significantly increased healthcare utilization of emergency department, inpatient, home health, outpatient, and total medical visits compared with the three higher quartiles groups (P

PURPOSE: To examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity. METHODS: 1635 sedentary adults aged 70 to 89 years from the Lifestyle Interventions and Independence for Elders (LIFE) single-blinded randomized, multi-center clinical trial, which compared a structured physical activity (PA) program to a health education (HE) program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400m, measured every 6 months for an average of 2.6 years. Secondary outcomes included persistent mobility disability (PMD), Short Physical Performance Battery (SPPB), 400m walk speed, and grip strength. RESULTS: A third of participants reported using FO at baseline (456, 28%; mean age, 78.5 years; 70.5% women). MMD was experienced by 131 participants (28.7%) in the FO group and 405 (34.4%) participants in the nonuser group. After adjusting for confounders, FO supplementation was associated with a lower risk (hazard ratio [HR], 0.78; 95% CI, 0.64–0.96) of incident MMD. However, there was no interaction (P= .19) between FO supplementation and PA intervention for MMD. For the secondary outcome of PMD, the intervention association differed by supplementation (P= .002) with PA intervention associations of (HR, 1.36; 95% CI, 0.83–2.23) for users and (HR, 0.61; 95% CI, 0.46–0.81) for nonusers. Changes in physical performance outcomes were not modified by baseline FO supplementation or combination with PA. CONCLUSIONS: FO supplementation was associated with a lower risk of major mobility disability in low to moderate functioning older adults. However, supplementation did not enhance the benefit of physical activity on risk of mobility disability. These results are hypothesis generating and need to be confirmed in randomized trials.

OBJECTIVES Proton pump inhibitors (PPIs) and histamine2 receptor antagonists (H2 RAs) are associated with pharmacologic effects that may be detrimental to mobility and response to physical activity. Mobility disability and injurious fall outcomes in PPI and H2 RA users were compared with nonusers in this secondary analysis of data from the Lifestyle Interventions for Elders (LIFE) study. METHODS Participants ages 70-89 years were randomized to a physical activity (PA) or successful aging intervention and evaluated by medication use. Confounders included baseline demographic characteristics, physical function, cognitive function, sleep quality, and acid reflux symptoms that were adjusted via propensity score weighting. Outcomes were incident and persistent major mobility disability (MMD and pMMD) and injurious falls. Weighted proportional hazard models evaluated independent and interaction effects of PPIs and H2 RAs. RESULTS No interaction was found between PPIs and H2 RAs and the PA intervention. Drug use associations were significant for H2 RAs (hazard ratio [HR] 1.74 [95% confidence interval [CI] 1.12-2.68]) and PPIs (HR 1.32 [95% CI 1.02-1.70]) compared with nonusers for pMMD. PPIs were associated with increased injurious falls compared with nonusers (HR 1.44 [95% CI 1.06-1.96]). Pooling of data from the H2 RA and PPI exposure groups showed a 26% increase in MMD (HR 1.26 [95% CI 1.07-1.48]), a 44% increase in pMMD (HR 1.44 [95% CI 1.16-1.77]), and a 48% increase in injurious falls (HR 1.48 [95% CI 1.15-1.91]) compared with nonusers. All direct comparisons between PPIs and H2 RAs were nonsignificant. CONCLUSIONS Compared with nonusers, participants using either PPIs or H2 RAs had an increased risk of MMD, pMMD, and injurious falls. It is not known if these effects are related to the individual pharmacology of each medication, reduced acid secretion, or the underlying disease state. Further study is required to determine causality.

Transcutaneous electrical stimulation (TES) is a frequently used adjunctive modality in dysphagia rehabilitation. Stimulating deeper swallowing muscles requires higher TES amplitude. However, TES amplitude is limited by maximum amplitude tolerance (MAT). Previous studies have reported high interindividual variability regarding MAT and perceived discomfort. This variability might be one of the potential reasons of conflicting outcomes in TES-based swallowing studies. MAT and perceived discomfort are influenced by a variety of biopsychological factors. The influence of these factors related to swallow applications is poorly understood. This study explored the relation of biopsychological factors with MAT and perceived discomfort related to TES in the submental area. A convenience sample of thirty community-dwelling older adults between 60 and 70 years of age provided data for this study. Gender, submental adipose tissue thickness, perceptual pain sensitivity, and pain-coping strategies were evaluated for each subject. Subsequently, MAT and perceived discomfort level were determined using TES on the submental area. Relation of different biopsychological variables with MAT and discomfort level was examined using Pearson and Spearman correlation, and Mann–Whitney U test. Results indicated that neither gender nor adipose thickness was related to MAT and perceived discomfort. Among studied pain-coping strategies, catastrophizing was significantly related to MAT(r = – 0.552, p

Background Lack of consensus on how to diagnose sarcopenia has limited the ability to diagnose this condition and hindered drug development. The Sarcopenia Definitions and Outcomes Consortium (SDOC) was formed to develop evidence-based diagnostic cut points for lean mass and/or muscle strength that identify people at increased risk of mobility disability. We describe here the proceedings of a meeting of SDOC and other experts to discuss strategic considerations in the development of evidence-based sarcopenia definition. Methods Presentations and panel discussions reviewed the usefulness of sarcopenia as a biomarker, the analytical approach used by SDOC to establish cut points, and preliminary findings, and provided strategic direction to develop an evidence-based definition of sarcopenia. Results The SDOC assembled data from eight epidemiological cohorts consisting of 18,831 participants, clinical populations from 10 randomized trials and observational studies, and 2 nationally representative cohorts. In preliminary assessments, grip strength or grip strength divided by body mass index was identified as discriminators of risk for mobility disability (walking speed Conclusions International consensus on an evidence-based definition of sarcopenia is needed. Grip strength—absolute or adjusted for body mass index—is an important discriminator of mobility disability and other endpoints. Additional research is needed to develop a predictive risk model that takes into account sarcopenia components as well as age, sex, race, and comorbidities.

Supplemental digital content is available in the text., Purpose The goal of this trial was to determine whether low-load blood flow–restricted (BFR) exercise of appendicular muscles induces a cross-transfer of effect to the trunk extensor (TE) muscles, such that low-load TE exercise would enhance TE size and function to a greater extent than standard low-load exercise in people with recurrent low back pain (LBP). We also investigated the direct effects of BFR exercise in the appendicular muscles. Methods Thirty-two adults with recurrent, nonspecific LBP were randomized into two groups: Appendicular BFR exercise (BFR exercise) or control exercise (CON exercise). All participants trained (two times per week) for 10 wk, with a 12-wk follow-up. Participants performed three sets of leg extension (LE), plantar flexion (PF), and elbow flexion (EF) exercises followed by low-load TE exercise without BFR. Outcome measures included magnetic resonance imaging–derived muscle size (quadriceps and TE), strength (LE, PF, EF, and TE), and endurance (LE and TE). Results There was no evidence for a cross-transfer of effect to the TE. There was also no statistically significant enhancement of limb skeletal muscle size or function of BFR relative to CON exercise at any time point; though, moderate effect sizes for BFR exercise were observed for enhanced muscle size and strength in the leg extensors. Conclusions Low-load BFR exercise of the appendicular muscles did not result in a cross-transfer of effect to the TE musculature. There was also no significant benefit of low-load BFR exercise on the appendicular muscle size and function, suggesting no benefit from low-load BFR exercise in adults with recurrent, nonspecific LBP.

Limited research in swallowing physiology has suggested that the most common existing transcutaneous electrical stimulation (TES) protocol (VitalStim) may not penetrate to layers of tissue to affect deep swallowing muscles. TES amplitude is the primary parameter that determines the depth of electrical current penetration (DECP). Preliminary work suggests that replacing a long-pulse duration with a short-pulse duration can increase maximum amplitude tolerance (MAT) within subjects' comfort level. Increasing MAT may indicate a higher DECP. The current study evaluates this premise in reference to the effects of varying pulse duration on lingual-palatal pressure during swallowing. Thirty healthy older adults (60-70 years of age) participated in this study. Each subject swallowed three trials of 10 mL pudding under three TES conditions: no stimulation, short-pulse duration, and long-pulse duration. TES was delivered using two pairs of surface electrodes on the submental muscles. MAT and perceived discomfort levels were identified separately for short and long-pulse TES conditions. Lingual-palatal peak pressure, pressure integral, and pressure duration were measured under each condition. Two-way repeated measures ANOVAs were conducted to identify within subject effects of TES condition and tongue bulb location. Lingual-palatal pressure and pressure integral were significantly reduced in the short-pulse duration condition. MAT was significantly higher in the short-pulse duration versus the long-pulse duration condition. Furthermore, MAT was significantly correlated with lingual-palatal pressure. Changing pulse duration had no significant impact on tongue pressure duration. Results suggest that a short-pulse duration may penetrate deeper into muscles involved in swallowing. The specific impact is reflected in a reduced upward pressure of the tongue on the palate during swallowing. This 'restrictive' effect of TES on tongue pressure may have the potential to be used during a resistive exercise paradigm for tongue elevation during swallowing.

Background The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)—a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD. Methods Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry. Results A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM. Conclusions Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD. Trial Registration clinicaltrials.gov Identifier NCT01072500

BACKGROUND. We provide the first examination of mitochondrial DNA (mtDNA) variants and pulmonary function in older persons. METHODS. Cross-sectional associations between mtDNA variants and pulmonary function were evaluated as a combined p-values meta-analysis, using data from two independent cohorts of older persons. The latter included white and black participants, aged ≥70 years, from the Lifestyle Interventions and Independence for Elders study (LIFE) (N=1,247) and the Health, Aging and Body Composition study (Health ABC) (N=731), respectively. Pulmonary function included the forced expiratory volume in one-second as a Z-score (FEV1z) and the maximal inspiratory pressure (MIP) in cm of water. RESULTS. In black participants, significant associations were found between mtDNA variants and MIP: m.7146A>G, COI (p=3E-5); m.7389T>C, COI (p=2E-4); m.15301G>A, CYB (p=9E-5); m.16265A>G, HV1 (p=9E-5); meta-analytical p-values

Background Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial. Methods The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50–100 mg/d or placebo (n = 43), (ii) fish oil 1,400–2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66). Results Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = −0.065 ± 0.116 [SE], 95% confidence interval [CI]: −0.293–0.163, p = .58) or fish oil (−0.020 ± 0.077, 95% CI: −0.171–0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (−0.025 ± 0.026, 95% CI: −0.076–0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: −0.025–0.044, p = .58) on walking speed (m/s). Conclusions These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation. Registration Clinicaltrials.gov NCT02676466.

Accelerometer-based fitness trackers and smartwatches are proliferating with incessant attention towards health tracking. Despite their growing popularity, accurately measuring hallmark measures of physical activities has yet to be accomplished in adults of all ages. In this work, we evaluated the performance of four machine learning models: decision tree, random forest, extreme gradient boosting (XGBoost) and least absolute shrinkage and selection operator (LASSO), to estimate the hallmark measures of physical activities in young (20–50 years), middle-aged (50–70 years], and older adults (70–89 years]. Our models were built to recognize physical activity types, recognize physical activity intensities, estimate energy expenditure (EE) and recognize individual physical activities using wrist-worn tri-axial accelerometer data (33 activities per participant) from a large sample of participants (n = 253, 62% women, aged 20–89 years old). Results showed that the machine learning models were quite accurate at recognizing physical activity type and intensity and estimating energy expenditure. However, models performed less optimally when recognizing individual physical activities. F1-Scores derived from XGBoost’s models were high for sedentary (0.955–0.973), locomotion (0.942–0.964) and lifestyle (0.913–0.949) activity types with no apparent difference across age groups. Low (0.919–0.947), light (0.813–0.828) and moderate (0.846–0.875) physical activity intensities were also recognized accurately. The root mean square error range for EE was approximately 1 equivalent of resting EE [0.835–1.009 METs]. Generally, random forest and XGBoost models outperformed other models. In conclusion, machine learning models to label physical activity types, activity intensity and energy expenditure are accurate and there are minimal differences in their performance across young, middle-aged and older adults.

Author(s): Gill, Thomas M; Bhasin, Shalender; Reuben, David B; Latham, Nancy K; Araujo, Katy; Ganz, David A; Boult, Chad; Wu, Albert W; Magaziner, Jay; Alexander, Neil; Wallace, Robert B; Miller, Michael E; Travison, Thomas G; Greenspan, Susan L; Gurwitz, Jerry H; Rich, Jeremy; Volpi, Elena; Waring, Stephen C; Manini, Todd M; Min, Lillian C; Teresi, Jeanne; Dykes, Patricia C; McMahon, Siobhan; McGloin, Joanne M; Skokos, Eleni A; Charpentier, Peter; Basaria, Shehzad; Duncan, Pamela W; Storer, Thomas W; Gazarian, Priscilla; Allore, Heather G; Dziura, James; Esserman, Denise; Carnie, Martha B; Hanson, Catherine; Ko, Fred; Resnick, Neil M; Wiggins, Jocelyn; Lu, Charles; Meng, Can; Goehring, Lori; Fagan, Maureen; Correa-de-Araujo, Rosaly; Casteel, Carri; Peduzzi, Peter; Greene, Erich J | Abstract: Background/objectivesIn the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability.DesignPragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries.SettingA total of 86 primary care practices within 10 U.S. healthcare systems.ParticipantsA random subsample of 743 persons aged 75 and older.MeasurementsThe well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument.ResultsParticipants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference.ConclusionsSTRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being.

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial&ndash, iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA4977) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score &le, 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores &ge, 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.

Background Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile. Methods We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed ( Results We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13–1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12–1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10–1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12–2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85–1.66). Conclusions High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.

Background The Lifestyle Interventions and Independence for Elders (LIFE) Study physical activity (PA) intervention was found to be cost-effective compared to health education (HE). However, long-term effects postintervention are unknown. Method This was a secondary analysis of LIFE Study data linked to Medicare claims data (2014–2016). Participants were linked via Social Security Numbers to Medicare claims data. Utilization and cost variables were analyzed using generalized linear models with negative binomial and Tweedie distributions. Unadjusted means and 95% confidence intervals were compared by year and overall stratified. Each model compared PA versus HE and adjusted for other baseline characteristics and stratified by study site. Additional models were stratified by baseline physical functioning assessment scores. Results Of the 1,635 LIFE Study participants, 804 (53.5%) were linked to Medicare claims with an average of 33 months of follow-up time during the 3-year data linkage period. Mean outpatient (6.6 vs 6.8), inpatient (0.40 vs 0.40), and other utilization metrics were similar between PA and HE groups. Costs were also similar for each group and each type of service, for example, outpatient: $2,070 versus $2,093 and inpatient: $4,704 versus $4,792. Regression results indicated no statistically significant differences between PA and HE groups. Conclusions While the LIFE Study demonstrated that PA reduced mobility disability in older adults and was cost-effective, it did not appear to affect long-term health care utilization costs posttrial. These findings suggest that it remains challenging to affect long-term health care costs using PA interventions effects.

Background The Enabling Reduction of Low-grade Inflammation in Seniors (ENRGISE) Pilot Study is a multicenter randomized clinical trial examining the feasibility of testing whether omega-3 fish oil (ω-3) and the angiotensin receptor blocker losartan alone or in combination can reduce inflammation and improve walking speed in older adults with mobility impairment. We describe recruitment methods and results. Methods Eligible participants were 70 years and older, had elevated interleukin-6 levels (2.5–30 pg/mL) and mobility impairment. Results Of those who responded to recruitment, 83% responded to mailings. A total of 5,424 telephone screens were completed; of these, 2,011 (37.1%) were eligible for further screening. The most common reasons for ineligibility at the telephone screens were lack of mobility impairment or use of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (n=1.789). Of the 1,305 initial screening visits, 1,087 participants had slow gait speed ( Conclusion Recruitment for ω-3 exceeded goals, but goals for the losartan and combination strata were not met due to the high proportion of participants taking angiotensin receptor blockers or angiotensin-converting enzyme inhibitors.

Key Points Question What is the risk of experiencing the prescribing cascade of treating dihydropyridine calcium channel blocker–induced lower-extremity edema with a loop diuretic? Findings In this cohort study of 1.2 million patients who initiated a dihydropyridine calcium channel blocker, excessive use of loop diuretics was found, which cannot be fully explained by secular trends or hypertension progression. This was particularly pronounced among patients who received a high dose of dihydropyridine calcium channel blockers. Meaning In this study, many patients received loop diuretics instead of a dose reduction or discontinuation of dihydropyridine calcium channel blockers, constituting a prescribing cascade. Future studies are needed to test strategies to mitigate or prevent prescribing cascades., This cohort study used prescription sequence symmetry analysis to assess the magnitude and characteristics of the prescribing cascade of treating dihydropyridine calcium channel blocker–induced lower-extremity edema with loop diuretics., Importance Calcium channel blockers, specifically dihydropyridine calcium channel blockers (DH CCBs, eg, amlodipine), may cause lower-extremity edema. Anecdotal reports suggest this may result in a prescribing cascade, where DH CCB–induced edema is treated with loop diuretics. Objective To assess the magnitude and characteristics of the DH CCB prescribing cascade. Design, Setting, and Participants This cohort study used a prescription sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of DH CCBs among patients aged 20 years or older without heart failure. Data from a private insurance claims database from 2005 to 2017 was analyzed. Use of loop diuretics associated with initiation of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other commonly used medications was used as negative controls. Data were analyzed from March 2019 through October 2019. Exposures Initiation of DH CCB or negative control medications. Main Outcomes and Measures The temporality of loop diuretic initiation relative to DH CCB or negative control initiation. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs were calculated using data from 360 days before and after initiation of DH CCBs. Results Among 1 206 093 DH CCB initiators, 55 818 patients (4.6%) (33 100 [59.3%] aged

Background The Lifestyle Interventions and Independence for Elders (LIFE) clinical trial demonstrated that a structured program of physical activity (PA) reduced mobility-disability in older adults by up to 28%. It remains unknown whether the benefits of LIFE PA can be translated to older adults at risk for mobility-disability in real-world community-based settings. To address this knowledge gap, we conducted the ENhancing independence using Group-based community interventions for healthy AGing in Elders (ENGAGE) pilot study and examined the safety, feasibility, and preliminary effectiveness of translating LIFE PA to a community-based senior center. Methods Forty older adults with severe lower extremity functional limitations (age: 76.9 ± 7.3 years; body mass index: 32.7 ± 8 kg/m2; 85% female; short physical performance battery score: 6.3 ± 2.2) were randomized to 24 weeks of PA or a health education control intervention. Results Community-based PA was safe (serious adverse events: PA vs health education, 0:2; nonserious adverse events: PA vs health education, 3:1) and participants successfully adhered to the PA intervention (65.2%). Compared to health education, PA participants who attended ≥25% of scheduled visits had meaningful and sustained short physical performance battery improvements at follow-up (between group short physical performance battery score differences: ~0.7 units). Conclusions ENGAGE has demonstrated the preliminary safety, feasibility, and effectiveness of LIFE PA in a real-world community-based setting. Larger-scale translational studies are needed to further disseminate the benefits of LIFE PA to vulnerable older adults in a variety of community-based settings.

OBJECTIVES Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at several mtDNA sites in complex I lead to inherited neurological neurologic diseases and brain magnetic resonance imaging (MRI) abnormalities. Here, we test the hypothesis that mtDNA heteroplasmy at these complex I sites is associated with depressive symptoms in the elderly. METHODS We examined platelet mtDNA heteroplasmy for associations with depressive symptoms among 137 participants over age 70 from the community-based Health, Aging and Body Composition Study. Depressive symptoms were assessed using the 10-point version of the Center for Epidemiologic Studies Depression Scale (CES-D 10). Complete mtDNA sequencing was performed and heteroplasmy derived for 5 mtDNA sites associated with neurologic mitochondrial diseases and tested for associations with depressive symptoms. RESULTS Of 5 candidate complex I mtDNA mutations examined for effects on depressive symptoms, increased heteroplasmy at m.13514A>G, ND5, was significantly associated with higher CES-D score (P = .01). A statistically significant interaction between m.13514A > G heteroplasmy and sex was detected (P = .04); in sex-stratified analyses, the impact of m.13514A>G heteroplasmy was stronger in male (P = .003) than in female (P = .98) participants. Men in highest tertile of mtDNA heteroplasmy exhibited significantly higher (P = .0001) mean ± SE CES-D 10 scores, 5.37 ± 0.58, when compared with those in the middle, 2.13 ± 0.52, and lowest tertiles, 2.47 ± 0.58. No associations between the 4 other candidate sites and depressive symptoms were observed. CONCLUSIONS Increased mtDNA heteroplasmy at m.13514A>G is associated with depressive symptoms in older men. Heteroplasmy may represent a novel biological risk factor for depression.

Objective: The purpose of this trial was to study the effects of chronic resveratrol use on cognitive function in humans. Design: The authors conducted a double-blind, Phase IIa randomized, placebo-controlled trial to obtain preliminary estimates of the effects of resveratrol supplementation on cognitive function over a 90-day period in older adults. Location: University of Florida in Gainesville, FL. Subjects: Sedentary, overweight older adults (N = 32; age range: 65–93 years, M age = 73.34 years, SD age = 7.02 years). Intervention: Participants were randomized to one of three treatment groups (placebo, 300 mg/day resveratrol, 1000 mg/day resveratrol) for 90 days. Outcome measures: Cognitive function was assessed before and after treatment using a well-characterized test battery: Trail Making, Digits Forward and Backward, Erikson-Flanker, Controlled Oral Word Association, Hopkins Verbal Learning Test-Revised, and Task Switching. Results: Psychomotor speed improved on the Trail Making Test part A in participants taking 1000 mg/day of resveratrol compared with participants in both the 300 mg/day condition and the placebo condition (p = 0.02). Conclusion: This pilot study suggests that 90 days of resveratrol supplementation at a dose of 1000/mg per day selectively improves psychomotor speed but does not significantly affect other domains of cognitive function in older adults. These findings provide modest support to further study the effects of resveratrol on cognitive function in older adults.

Background Structured physical activity interventions delay the onset of disability for at-risk older adults. However, it is not known if at-risk older adults continue to participate in physical activity or maintain mobility benefits after cessation of structured intervention. Methods One thousand six hundred and thirty-five sedentary men and women aged 70-89 years with Short Physical Performance Battery (SPPB) scores of 9 or less and able to walk 400 m were randomized to a structured, moderate-intensity physical activity (PA) program consisting of center-based (twice/week) and home-based (three to four times per week) aerobic, resistance, and flexibility training or a health education (HE) program combined with upper extremity stretching. Results Most of the participants (88% of HE and 87% of PA) returned for a follow-up visit (POST) 1 year after cessation of formal intervention. The HE group reported about 1-hour less activity per week than the PA group at end of intervention (LAST TRIAL; -68.9; 95% confidence interval [CI] = -86.5 to -51.3) but similar weekly activity at POST (-13.5; 95% CI = -29.5 to 2.47). SPPB did not differ between the two groups at LAST TRIAL (-0.06; 95% CI = -0.31 to 0.19) nor POST (-0.18; 95% CI = -0.45 to 0.088). Conclusions Although sedentary at-risk older adults increased their physical activity during a structured physical activity intervention, they did not continue at this level following the cessation of intervention. Future exercise interventions need to include novel methods to support older adults in continued physical activity following structured interventions.

High-load resistance training (HL) may be contraindicated in older adults due to pre-existing health conditions (e.g. osteoarthritis). Low-load blood flow restricted (BFR) resistance training offers an alternative to HL with potentially similar strength improvement.To compare muscle strength, cross-sectional area (CSA), physical function, and quality of life (QOL) following 12-weeks of HL or BFR training in older adults at risk of mobility limitations.Thirty-six males and females (mean: 75.6years 95% confidence interval: [73.4-78.5], 1.67m [1.64-1.70], 74.3kg [69.8-78.8]) were randomly assigned to HL (70% of one repetition maximum [1-RM]) or low-load BFR (30% 1-RM coupled with a vascular restriction) exercise for the knee extensors and flexors twice per week for 12weeks. A control (CON) group performed light upper body resistance and flexibility training. Muscle strength, CSA of the quadriceps, 400-m walking speed, Short Physical Performance Battery (SPPB), and QOL were assessed before, midway and after training.Within 6-weeks of HL training, increases in all strength measures and CSA were evident and the gains were significantly greater than the CON group (P0.05). The BFR group had strength increases in leg extension and leg press 1-RM tests, but were significantly lower in leg extension isometric maximum voluntary contraction (MVC) and leg extension 1-RM than the HL group (P0.01). At 12-weeks HL and BFR training did not differ in MVC (P=0.14). Walking speed increased 4% among all training groups (P0.01) and no changes were observed for overall SPPB score and QOL (P0.05).Both training programs resulted in muscle CSA improvements and HL training had more pronounced strength gains than BFR training after 6-weeks and were more similar to BFR after 12-weeks of training. These changes in both groups did not transfer to improvements in QOL, SPPB, and walking speed. Since both programs result in strength and CSA gains, albeit at different rates, future research should consider using a combination of HL and BFR training in older adults with profound muscle weakness and mobility limitations.

Background Greater brain network integrity may associate with physically active lifestyles. Three resting state networks may provide unique insights into known physical activity-mediated brain health benefits: the default mode network (involved with self-monitoring), the salience network (involved in orienting oneself to salient external and internal stimuli), and the central executive network (responsible for higher level cognitive task). The current study explored relationships between system-wide neural network integrity measured by functional magnetic resonance imaging and objectively-measured physical activity. We hypothesize connectivity patterns as measured by fMRI networks will relate to actigraphy markers such that 1) there will be higher connectivity within the central executive network in more physically active individuals, and 2) there will be higher connectivity within the default mode network and salience network in those with higher levels of physical activity. Methods Eighteen non-demented older adults with orthopedic pain (age 67.11 ± 5.61, 50% female, education 15.94 ± 2.51 years) completed brain magnetic resonance imaging, and wore an actigraphy device to objectively measure types of physical and sedentary engagement. Results Results showed a negative relationship between central executive network connectivity and sedentary time (β = ‐0.108, p = .039), and a positive relationship with both moderate-to-vigorous physical activity (β = 0.629, p = .029) and total activity time (β = 0.645, p = .039). Results also showed positive relationships for the default mode network (β = 0.588, p = .033) and the salience network (β = 0.608, p = .037) with mean cadence (i.e. steps per minute). Conclusions Our work adds to the existing literature on specific types of activity measurement (i.e. sedentary time, cadence and moderate-to-vigorous physical activity) which will be useful for interventions aimed at improving the integrity of underlying neural networks.

To examine the effect of a long-term structured physical activity (PA) intervention on accelerometer-derived metrics of activity pattern changes in mobility-impaired older adults.Participants were randomized to either a PA or health education (HE) program. The PA intervention included a walking regimen with strength, flexibility, and balance training. The HE program featured health-related discussions and a brief upper body stretching routine. Participants (n = 1341) wore a hip-worn accelerometer for ≥10 h·d for ≥3 d at baseline and again at 6, 12, and 24 months postrandomization. Total PA (TPA)-defined as movements registering 100+ counts per minute-was segmented into the following intensities: low-light PA (LLPA; 100-759 counts per minute), high light PA (HLPA; 760-1040 counts per minute), low moderate PA (LMPA; 1041-2019 counts per minute), and high moderate and greater PA (HMPA; 2020+ counts per minute). Patterns of activity were characterized as bouts (defined as the consecutive minutes within an intensity).Across groups, TPA decreased an average of 74 min·wk annually. The PA intervention attenuated this effect (PA = -68 vs HE: -112 min·wk, P = 0.002). This attenuation shifted TPA composition by increasing time in LLPA (10+ bouts increased 6 min·wk), HLPA (1+, 2+, 5+, and 10+ bouts increased 6, 3, 2, and 1 min·wk, respectively), LMPA (1+, 2+, 5+, and 10+ bouts increased: 19, 17,16, and 8 min·wk, respectively), and HMPA (1+, 2+, 5+, and 10+ bouts increased 23, 21, 17, and 14 min·wk, respectively).The PA intervention increased PA by shifting the composition of activity toward higher-intensity activity in longer-duration bouts. However, a long-term structured PA intervention did not completely eliminate overall declines in total daily activity experienced by mobility-impaired older adults.

Objectives To examine associations between objectively measured physical activity (PA) and incidence of major mobility disability (MMD) and persistent MMD (PMMD) in older adults in the Lifestyle Interventions and Independence for Elders (LIFE) Study. Design Prospective cohort of individuals aged 65 and older undergoing structured PA intervention or health education. Setting The LIFE Study was a multicenter (eight sites) randomized controlled trial designed to compare the efficacy of a long-term structured PA intervention with that of a health education (HE) program in reducing the incidence of MMD in mobility-limited older adults. Participants LIFE Study participants (n = 1,590) had a mean age±standard deviation of 78.9 ± 5.2, low levels of PA, and measured mobility-relevant functional impairment at baseline. Measurements Activity data were collected using hip-worn 7-day accelerometers at baseline and 6, 12, and 24 months after randomization to test for associations with incident MMD and PMMD (≥2 consecutive instances of MMD). Results At baseline, every 30 minutes spent being sedentary (

Background The objective assessment of major mobility disability (objective MMD) by a 400-m walk test (400 MWT) is important but not always practical. Previous research on the relationship between self-reported MMD (SR MMD) and objective MMD is sparse and limited to cross-sectional data. Methods We evaluated agreement between SR MMD and objective MMD using longitudinal data from the Lifestyle Interventions for Elders (LIFE) study. The SR MMD indices were defined based on having a lot of difficulty or inability to walk a quarter of a mile (SR-1/4MILE), walk several blocks (SR-BLOCKS), and climb one flight of stairs (SR-STAIRS). Results Using objective MMD as the gold standard, SR-1/4MILE and SR-BLOCKS had relatively low sensitivity (around 0.4) and high specificity (around 0.9) for prevalence. Their overall sensitivity and specificity for cumulative incident objective MMD were approximately 0.6 and 0.8, respectively. While the annual probability of staying MMD free was similar for objective MMD, SR-1/4MILE, and SR-BLOCKS (90% for all), the probability of recovering from SR MMD was higher (50%) than that of objective MMD (22%). The development of objective MMD (439 events), SR-1/4MILE (356 events), and SR-BLOCKS (379 events) had a similar trajectory over time with substantially overlapping survival curves. SR-STAIRS generally did not agree well with objective MMD. Incorporating SR-STAIRS with either SR-1/4MILE or SR-BLOCKS did not significantly improve the agreement between SR MMD and objective MMD. Conclusions Simple SR-1/4MILE and SR-BLOCKS are reasonable candidates to define MMD if the primary outcome of interest is incident MMD.

BACKGROUND: An important decision with accelerometry is the threshold in counts per minute (CPM) used to define moderate to vigorous physical activity (MVPA). We explore the ability of different thresholds to track changes in MVPA due to a physical activity (PA) intervention among older adults with compromised function: 760 CPM, 1,041 CPM, and an individualized threshold. We also evaluate the ability of change in accelerometry and self-reported PA to attenuate treatment effects on major mobility disability (MMD). METHODS: Data from a week of hip worn accelerometers and self-reported PA data (30-day recall) were examined from baseline, 6-, 12-, and 24-months of follow-up on 1,528 older adults. Participants were randomized to either PA or Health Education (HE). MMD was objectively defined by loss of ability to walk 400 m during the follow-up. RESULTS: The three thresholds yielded similar and higher levels of MVPA for PA than HE (p < .001), however, this difference was significantly attenuated in participants with lower levels of physical function. Self-reported PA that captured both walking and strength training totally attenuated the intervention effect for MMD, an 18% reduction to a 3% increase. Accelerometer CPMs showed less attenuation of the intervention effect. CONCLUSIONS: Accelerometry assessment within the LIFE study was not sensitive to change in level in physical activity for older adults with very low levels of physical function. A combination of self-report and objective measures are recommended for use in physical activity intervention studies of the elderly; limitations of accelerometry deserve closer attention.

OBJECTIVES: To investigate whether baseline social participation modifies the effect of a long-term structured physical activity (PA) program on major mobility disability (MMD). METHODS: 1,635 sedentary adults (70–89 years) with physical limitations were randomized to either a structured PA or health education (HE) intervention. Social participation was defined categorically at baseline. High social participation was defined as attending organized group functions at least once per week and visiting with noncohabitating friends and family ≥7 hr per week. Anything less was considered limited social participation. Participants performed a standardized walking test at baseline and every 6 months for up to 42 months. MMD was defined as the loss in the ability to walk 400 m. RESULTS: There was a significant intervention by social participation interaction (p = .003). Among individuals with high levels of social participation, those randomized to PA had significantly lower incidence of MMD (hazard ratio [HR], 0.43 [95% confidence interval (CI), 0.27–0.68]; p < .01) than those randomized to HE. Individuals with limited social participation showed no mobility benefit of the PA intervention when compared with their HE counterparts (HR, 0.92 [95% CI, 0.77–1.11]; p = .40). DISCUSSION: Our findings suggest that baseline social participation is an important factor for the success of a PA intervention aimed at delaying mobility disability.

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

Background Physical activity (PA) reduces the rate of mobility disability, compared with health education (HE), in at risk older adults. It is important to understand aspects of performance contributing to this benefit. Objective To evaluate intervention effects on tertiary physical performance outcomes. Design The Lifestyle Interventions and Independence for Elders (LIFE) was a multi-centered, single-blind randomized trial of older adults. Setting Eight field centers throughout the United States. Participants 1635 adults aged 78.9 ± 5.2 years, 67.2% women at risk for mobility disability (Short Physical Performance Battery [SPPB]

We investigated the acute myogenic response to resistance exercise with and without blood-flow restriction (BFR). Six men and women (age, 22 ± 1 years) performed unilateral knee extensions at 40% of 1-repetition maximum with or without (CNTRL) BFR applied via pressure cuff inflated to 220 mm Hg. Muscle biopsies were collected at 4 h and 24 h postexercise. Addition of BFR increased myoD and c-Met messenger RNA expression relative to CNTRL. Expression of hepatocyte growth factor protein was significantly higher following CNTRL.

Whether disruption of iron metabolism is implicated in human muscle aging is presently unclear. We explored the relationship among iron metabolism, muscle mitochondrial homeostasis, inflammation, and physical function in older adults and young controls. Eleven young and 23 older men and women were included. Older adults were classified into high&ndash, functioning (HF) and low&ndash, functioning (LF) groups according to their Short Physical Performance Battery score. Vastus lateralis muscle biopsies were assayed for total iron content, expression of 8-oxoguanine and DNA glycosylase (OGG1), 3-nitrotyrosine (3-NT) levels, and mitochondrial DNA (mtDNA) content and damage. Circulating ferritin and hepcidin levels were also quantified. Muscle iron levels were greater in the old group. Protein expression of transferrin receptor 1, Zrt-Irt-like protein (ZIP) 8, and ZIP14 were lower in old participants. Circulating levels of ferritin, hepcidin, interleukin 6 (IL6), and C-reactive protein were higher in the old group. Old participants showed lower mtDNA content and greater mtDNA damage. OGG1 protein expression declined with age, whereas 3-NT levels were greater in old participants. Finally, a negative correlation was determined between ZIP14 expression and circulating IL6 levels in LF older adults. None of assayed parameters differed between HF and LF participants. Our findings suggest that muscle iron homeostasis is altered in old age, which might contribute to loss of mtDNA stability. Muscle iron metabolism may therefore represent a target for interventions against muscle aging.

OBJECTIVES: Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht2); and slowness (walking speed

Older adults are at high risk of developing cardiovascular disease (CVD). Pre-clinical studies indicate that resveratrol (RSV), a polyphenol commonly found in grapes and red wine, may help prevent development of CVD. Based on our previous reports where the 300 mg and 1000 mg doses appeared safe and improved psychomotor function in a dose-dependent manner, our hypothesis was that RSV would reduce biomarkers of CVD risk in overweight, but otherwise healthy older adults and that 1000 mg would lower CVD biomarkers >300 mg. This analysis was performed on samples from older participants (65 years and older) who were randomized to a 90 day RSV treatment with 300 mg (n = 10), 1000 mg (n = 9) or placebo (n = 10). We measured levels of CVD risk biomarkers i.e. oxidized low-density lipoprotein (oxLDL), soluble E-selectin-1 (sE-selectin), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), total plasminogen activator inhibitor (tPAI-1). Statistical significance was set at p Both sVCAM-1 and tPAI increased significantly more in the 1000 mg vs. 300 mg and placebo groups. Other biomarkers (300 mg vs. 1000 mg vs. placebo: oxLDL, sEselectin-1 and sICAM-1) followed the same trend toward higher levels in the 1000 mg group compared to the 300 mg and placebo groups, without reaching statistical significance. This pilot project suggests that a higher dose of RSV may increase the levels of CVD risk biomarkers in overweight older adults. Given no change in the CVD risk biomarkers in response to a lower dose, future studies should test the effects of different doses of RSV to evaluate potential detrimental effects of higher doses on CVD biomarkers and measures of cardiovascular function in older adults at risk for CVD.

Background Sarcopenia is often conceptualized as a precursor to loss of mobility, but its effect on recovery of mobility after a hip fracture is unknown. We determined the prevalence of low muscle strength (weakness) after hip fracture using putative sarcopenia metrics (absolute grip strength, and grip strength normalized to body mass index, total body fat, arm lean mass, and weight) identified by the Sarcopenia Definitions and Outcomes Consortium (SDOC). Methods We examined two well-characterized hip fracture cohorts of community-dwelling older adults from the Baltimore Hip Studies (BHS). The prevalence of muscle weakness was assessed using the SDOC cut points compared to published definitions at 2 and 6 months postfracture. We assessed associations of 2-month weakness with 6-month walking speed Results Two hundred and forty-six participants (192 women; 54 men) were included; mean (SD) age of 81 (8) for women and 78 (7) for men. At 2 months, 91% women and 78% men exhibited slow walking speed (< 0.6 m/s). SDOC grip strength standardized by weight ( Conclusions SDOC cut points for grip strength standardized to weight provided consistent indication of poor walking speed performance post-hip fracture.

BackgroundPersons with HIV may experience greater mobility limitations than uninfected populations. Accurate tools are needed to identify persons at greatest risk of decline. We evaluated the performance of novel muscle weakness metrics (grip, grip/body mass index [BMI], grip/weight, grip/total body fat, grip/arm lean mass) and association with slowness and falls in older persons with or at risk for HIV infection as part of the work of the Sarcopenia Definitions and Outcomes Consortium (SDOC).MethodsWe assessed the prevalence of sarcopenia among 398 men (200 HIV+, 198 HIV−) from the Multicenter AIDS Cohort Study and 247 women (162 HIV+, 85 HIV−) from the Women’s Interagency HIV Study using previously validated muscle weakness metrics discriminative of slowness. Sensitivity and specificity were used to compare new muscle weakness and slowness criteria to previously proposed sarcopenia definitions.ResultsThe prevalence of muscle weakness ranged from 16% to 66% among men and 0% to 47% among women. Grip/BMI was associated with slowness among men with HIV only. Grip/BMI had low sensitivity (25%–30%) with moderate to high specificity (68%–89%) for discriminating of slowness; all proposed metrics had poor performance in the discrimination of slowness (area under the curve [AUC] < 0.62) or fall status (AUC < 0.56). The combination of muscle weakness and slowness was not significantly associated with falls (p ≥ .36), with a low sensitivity in identifying those sustaining one or more falls (sensitivity ≤ 16%).DiscussionClinical utility of new sarcopenia metrics for identification of slowness or falls in men and women with or at risk for HIV is limited, given their low sensitivity.

A growing body of evidence indicates that time restricted feeding (TRF), a popular form of intermittent fasting, can activate similar biological pathways as caloric restriction, the only intervention consistently found to extend healthy lifespan in a variety of species. Thus, TRF may have the potential to also improve function in older adults. Given the challenges many individuals have in following calorie restriction regimens over long-time periods, evaluation of alternative approaches that may produce weight loss and improve function in overweight, older adults is important. Ten overweight, sedentary older adults (&ge, 65 years) at risk for, or with mobility impairments, defined by slow gait speed (&lt, 1.0 m/s) participated in this trial. All participants received the intervention and were instructed to fast for approximately 16 h per day over the entire four-week intervention. Outcomes included changes in body weight, waist circumference, cognitive and physical function, health-related quality of life, and adverse events. Adherence levels were high (mean = 84%) based on days goal was met, and mean weight loss was 2.6 kg (p &lt, 0.01). Since body composition was not measured in this study, it is unclear if the observed weight loss was due to loss of fat mass, muscle mass, or the combination of fat and muscle mass. There were no significant changes in other outcomes, however, there were clinically meaningful changes in walking speed and improvements in quality of life, with few reported adverse events. The findings of this pilot study suggest that time restricted feeding is an acceptable and feasible eating pattern for overweight, sedentary older adults to follow.

Background Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may protect against aging-related decline. This study directly compared ACEis and ARBs on associations with risk of mobility disability in older adults when combined with a physical activity intervention. Methods This was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) trial. Participants aged 70–89 years were randomized to a physical activity or health education intervention. Outcomes included incident and persistent major mobility disability, injurious falls, short physical performance battery, and gait speed. For this analysis, only participants who reported ACEi or ARB use at baseline were included. Baseline differences between ACEi and ARB groups were adjusted for using inverse probability of treatment weights. Weighted Cox proportional hazard models and analysis of covariance models were used to evaluate the independent effects of medications and interaction effects with the intervention on each outcome. Results Of 1,635 participants in the Lifestyle Interventions and Independence for Elders study, 796 used either an ACEi (496, 62.3%) or ARB (300, 37.7%). Compared with ACEi users, ARB users had 28% lower risk (hazard ratio [HR] = 0.72 [0.60–0.85]) of incident major mobility disability and 35% (HR = 0.65 [0.52–0.82]) lower risk of persistent major mobility disability whereas no interaction between medication use and intervention was observed. Risk of injurious falls and changes in short physical performance battery or gait speed were not different between ARB and ACEi users. Conclusions These results suggest that ARBs may protect from major mobility disability by other mechanisms than improving physical performance.

Background There has been an increasing interest in understanding the usefulness of wrist-based accelerometer data for physical activity (PA) assessment due to the ease of use and higher user compliance than other body placements. PA assessment studies have relied on machine learning methods which take accelerometer data in forms of variables, or feature vectors. Methods In this work, we introduce automated shape feature derivation methods to transform epochs of accelerometer data into feature vectors. As the first step, recurring patterns in the collected data are identified and placed in a codebook. Similarities between epochs of accelerometer data and codebook’s patterns are the basis of feature calculations. In this paper, we demonstrate supervised and unsupervised approaches to learn codebooks. We evaluated these methods and compared them with the standard statistical measures for PA assessment. The experiments were performed on 146 participants who wore an ActiGraph GT3X+ accelerometer on the right wrist and performed 33 activities of daily living. Results Our evaluations show that the shape feature derivation methods were able to perform comparably with the standard wrist model (F1-score: 0.89) for identifying sedentary PAs (F1-scores of 0.86 and 0.85 for supervised and unsupervised methods, respectively). This was also observed for identifying locomotion activities (F1-scores: 0.87, 0.83, and 0.81 for the standard wrist, supervised, unsupervised models, respectively). All the wrist models were able to estimate energy expenditure required for PAs with low error (rMSE: 0.90, 0.93, and 0.90 for the standard wrist, supervised, and unsupervised models, respectively). Conclusion The automated shape feature derivation methods offer insights into the performed activities by providing a summary of repeating patterns in the accelerometer data. Furthermore, they could be used as efficient alternatives (or additions) for manually engineered features, especially important for cases where the latter fail to provide sufficient information to machine learning methods for PA assessment.

IMPORTANCE: Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor. OBJECTIVE: To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people with PAD vs high-intensity home-based walking exercise that induces ischemic leg symptoms and vs a nonexercise control. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial conducted at 4 US centers and including 305 participants. Enrollment occurred between September 25, 2015, and December 11, 2019; final follow-up was October 7, 2020. INTERVENTIONS: Participants with PAD were randomized to low-intensity walking exercise (n = 116), high-intensity walking exercise (n = 124), or nonexercise control (n = 65) for 12 months. Both exercise groups were asked to walk for exercise in an unsupervised setting 5 times per week for up to 50 minutes per session wearing an accelerometer to document exercise intensity and time. The low-intensity group walked at a pace without ischemic leg symptoms. The high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms. Accelerometer data were viewable to a coach who telephoned participants weekly for 12 months and helped them adhere to their prescribed exercise. The nonexercise control group received weekly educational telephone calls for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was mean change in 6-minute walk distance at 12 months (minimum clinically important difference, 8-20 m). RESULTS: Among 305 randomized patients (mean age, 69.3 [SD, 9.5] years, 146 [47.9%] women, 181 [59.3%] Black patients), 250 (82%) completed 12-month follow-up. The 6-minute walk distance changed from 332.1 m at baseline to 327.5 m at 12-month follow-up in the low-intensity exercise group (within-group mean change, −6.4 m [95% CI, −21.5 to 8.8 m]; P = .34) and from 338.1 m to 371.2 m in the high-intensity exercise group (within-group mean change, 34.5 m [95% CI, 20.1 to 48.9 m]; P

Background Chronic inflammation, changes in body composition, and declining physical function are hallmarks of the ageing process. The aim of the present study was to provide a preliminary characterisation of the relationship among these age-related phenomena via multivariate modelling. Methods Thirty-five old adults (OAs) and 17 young adults (YAs) were enrolled. The volume of skeletal muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) of the thigh was quantified by three-dimensional magnetic resonance imaging. Muscle strength was measured by knee extension strength testing. In OAs, physical performance was further assessed via the Short Physical Performance Battery (SPPB). Multi-block partial least squares-discriminant analysis (PLS-DA) was employed to explore the relationship among inflammatory profiles and functional and imaging parameters. Double cross-validation procedures were used to validate the predictive ability of the PLS-DA model. Results The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 92.3% in calibration (94.1% in YAs and 91.4% in OAs), 84.6% in internal validation (95.3% in YAs and 78.5% in OAs), and 82.6% in external validation (94% in YAs and 76.9% in OAs). Relative to YAs, OAs were characterised by smaller muscle volume, greater IMAT volume, lower muscle strength, and higher levels of myeloperoxidase, P-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Compared with OAs with SPPB >8, those scoring ≤8 were characterised by smaller muscle volume, greater SAT volume, lower muscle strength, and higher levels of interleukin 1 beta, 6, 10, 12, 13, tumour necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor. Conclusions Multi-block PLS-DA identified distinct patterns of relationships among circulating cytokines and functional and imaging parameters in persons of different ages and varying levels of physical performance. The longitudinal implementation of such an innovative strategy could allow for the tracking of health status over time, the early detection of deviations in health trajectories, and the monitoring of response to treatments.

// Nicholas R. Wawrzyniak 1 , Anna-Maria Joseph 2 , David G. Levin 1 , David M. Gundermann 2 , Christiaan Leeuwenburgh 2 , Bhanuprasad Sandesara 2 , Todd M. Manini 2 and Peter J. Adhihetty 1 1 Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA 2 Department of Aging and Geriatric Research, Division of Biology of Aging, University of Florida, Gainesville, Florida, USA Correspondence to: Peter J. Adhihetty, email: // Todd M. Manini, email: // Keywords : fatigue; skeletal muscle; mitochondria; PGC-1α; Gerotarget Received : January 11, 2016 Accepted : June 09, 2016 Published : July 18, 2016 Abstract Fatigue is a symptom of many diseases, but it can also manifest as a unique medical condition, such as idiopathic chronic fatigue (ICF). While the prevalence of ICF increases with age, mitochondrial content and function decline with age, which may contribute to ICF. The purpose of this study was to determine whether skeletal muscle mitochondrial dysregulation and oxidative stress is linked to ICF in older adults. Sedentary, old adults ( n = 48, age 72.4 ± 5.3 years) were categorized into ICF and non-fatigued (NF) groups based on the FACIT-Fatigue questionnaire. ICF individuals had a FACIT score one standard deviation below the mean for non-anemic adults > 65 years and were excluded according to CDC diagnostic criteria for ICF. Vastus lateralis muscle biopsies were analyzed, showing reductions in mitochondrial content and suppression of mitochondrial regulatory proteins Sirt3, PGC-1α, NRF-1, and cytochrome c in ICF compared to NF. Additionally, mitochondrial morphology proteins, antioxidant enzymes, and lipid peroxidation were unchanged in ICF individuals. Our data suggests older adults with ICF have reduced skeletal muscle mitochondrial content and biogenesis signaling that cannot be accounted for by increased oxidative damage.

Objectives To determine whether moderate-intensity physical activity (PA) and health education (HE) are differentially associated with categories of hospitalizations or subgroups of participants. Design Multicenter randomized controlled trial in which participants were randomized to a PA or HE program for an average of 2.6 years. Setting Eight field centers. Participants Sedentary men and women aged 70–89 with lower extremity physical limitations but able to walk 400-m in 15 minutes or less (N = 1,635). Interventions Structured, moderate-intensity PA (n = 818) at a center (2×/wk) and at home (3–4×/wk) that included aerobic, strength, balance, and flexibility training or HE (n = 817) of educational workshops and upper extremity stretching exercises. Measurements All-cause inpatient hospitalizations ascertained at 6-month intervals. Results There were 1,458 hospitalizations (49.1% of PA, 44.4% of HE; risk difference = 4.68%, 95% confidence interval (CI) = −0.18–9.54; hazard ratio (HR) = 1.16, 95% CI = 1.00–1.34). The intervention effect on incident hospitalization did not differ according to race, sex, Short Physical Performance Battery score, age, or history of cardiovascular disease or diabetes mellitus. PA was associated with higher rates of hospitalization in the middle baseline gait speed category, than HE ( 1.0 m/s: HR = 1.05, 95% CI = 0.67–1.65; interaction P = .005). Conclusion A PA program in older adults at risk for mobility disability did not lead to a different risk of specific types of hospitalizations than a HE program overall. Baseline gait speed may be a marker for risk of hospitalization during a PA intervention, because individuals with moderate baseline gait speed in the PA group had slightly higher rates of hospitalization than those in the HE group. Trial Registration: ClinicalTrials.gov identifier: NCT01072500.

Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect. Methods We used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline. Results After adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels (P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score (P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively). Conclusions A 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging. Trial registration Clinicaltrials.gov, NCT01072500 Electronic supplementary material The online version of this article (10.1186/s12916-018-1174-8) contains supplementary material, which is available to authorized users.

Declines in walking speed are associated with a variety of poor health outcomes including disability, comorbidity, and mortality. While genetic factors are putative contributors to variability in walking, few genetic loci have been identified for this trait. We examined the role of mitochondrial genomic variation on walking speed by sequencing the entire mitochondrial DNA (mtDNA). Data were meta-analyzed from 1758 Lifestyle Interventions and Independence for Elders (LIFE) Study and replication data from 730 Health, Aging, and Body Composition (HABC) Study participants with baseline walking speed information. Participants were 69+ years old of diverse racial backgrounds (African, European, and other race/ethnic groups) and had a wide range of mean walking speeds [4–6 m (0.78–1.09 m/s) and 400 m (0.83–1.24 m/s)]. Meta-analysis across studies and racial groups showed that m.12705C>T, ND5 variant was significantly associated (p A, ND2 and m.309C>CT, HV2 variants at short and long distances, respectively. All results remained statistically significant after multiple comparisons adjustment for 499 mtDNA variants. The m.12705C>T variant can be traced to the beginnings of human global migration and that cells carrying this variant display altered tRNA expression. Significant pooled effects related to stopping during the long-distance walk test were observed across OXPHOS complexes I (p = 0.0017) and III (p = 0.0048). These results suggest that mtDNA-encoded variants are associated with differences in walking speed among older adults, potentially identifying those at risk of developing mobility impairments.