Comparison of a Multi-Component Physical Function Battery to Usual Walking Speed for Assessing Lower Extremity Function and Mobility Limitation in Older Adults.

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.

Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults - A pilot study.

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 < 0.05. 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.

Effects of Fermented Papaya Preparation (FPP) on Safety Outcomes in Older Adults - A Short Report of a Placebo-Controlled Clinical Trial.

Fermented Papaya Preparation (FPP®) has shown antioxidative and anti-inflammatory effects in preclinical and clinical aging studies. However, clinical trials are needed to fully evaluate the safety of FPP® in moderate-functioning, generally healthy older adults. In this randomized (9g/day of FPP® or placebo), crossover design study, we enrolled 30 older moderate-functioning older adults (70-100 years old). The participants completed both a treatment and a placebo condition. After eight (8) weeks on each of these regimens (with a 4-week wash-out period in between), participants had their venous blood drawn for assessment of blood chemistries, metabolic outcomes and inflammatory biomarkers. Participants were asked to report any adverse events during the course of the study and complete post-treatment outcome assessments for anthropometric and metabolic outcomes. The major finding related to safety was that there were no adverse changes in blood chemistries and few adverse events in the FPP® condition, which did not differ from placebo (p>0.05). There were no serious adverse effects in either condition. Twenty-nine (29) participants (mean age 78.2±5.3 yrs) completed the study with 94% adherence to the dosing regimen. There were no significant effects of FPP® on anthropometric and metabolic outcomes. In addition, no effects on markers of inflammation were observed. Our trial demonstrates FPP® supplementation is safe and feasible in adults ages 70 years and older. Based on these findings and the positive effects FPP has demonstrated in previous trials, future trials should examine the effects of FPP® in older adults with impaired health status and/or older adults who may have insufficient anti-oxidant protection due to their genetic background.

Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis.

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68 pg/ml), ARBs (-0.37 pg/ml) and omega-3 (-0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

A New Adaptive Home-based Exercise Technology among Older Adults Living in Nursing Home: A Pilot Study on Feasibility, Acceptability and Physical Performance.

OBJECTIVES: To explore the feasibility and acceptability of a new home-based exercise technology among older adults and to evaluate its efficacy on physical performance measures. DESIGN: Longitudinal clinical trial. SETTING: Oak Hammock at the University of Florida, a nursing home located in Gainesville, Florida. PARTICIPANTS: Twelve pre-disabled older adults (≥75 years) living in a nursing home with a Short Physical Performance Battery (SPPB) score between 6 and 9 and no diagnosis of dementia. INTERVENTION: Thirty minutes of light intensity exercise (aerobic, strength and balance) two times per week for four weeks using a home-based physical activity technology called Jintronix. MEASUREMENTS: Feasibility and acceptability were assessed through a 9-item self-administered questionnaire and by exploring the percentage of quality of movements and time performing exercise which was calculated automatically by Jintronix technology. Physical performance measures were assessed through the SPPB score at baseline, after 4 weeks of intervention and after 3 months from the completion of the intervention. RESULTS: Twelve older adults (80.5±4.2 years old) performed light intensity exercise with Jintronix for a total of 51.9±7.9 minutes per week. Participants reached 87% score of quality of movements in strength and balance exercises, a global appreciation score of 91.7% and a global difficulty score of 36%. Compared to baseline, there was a significant improvement in SPPB score at the end of the intervention and at 3 months following the completion of the exercise program (0.67±0.98 and 1.08±0.99 respectively, p-value <0.05). CONCLUSION: Jintronix technology is feasible and acceptable among pre-disabled older adults without dementia living in nursing home and is beneficial in improving their physical performance.

A new approach to disentangle genetic and epigenetic components on disease comorbidities: studying correlation between genotypic and phenotypic disease networks.

Disease comorbidity is a result of complex epigenetic interplay. A disease is rarely a consequence of an abnormality in a single gene; complex pathways to disease patterns emerge from gene-gene interactions and gene-environment interactions. Understanding these mechanisms of disease and comorbidity development, breaking down them into clusters and disentangling the epigenetic - actionable - components, is of utter importance from a public health perspective. With the increase in the average life expectancy, healthy aging becomes a primary objective, from both an individual (i.e. quality of life) and a societal (i.e. healthcare costs) standpoint. Many studies have analyzed disease networks based on common altered genes, on protein-protein interactions, or on shared disease comorbidites, i.e. phenotypic disease networks. In this work we aim at studying the relations between genotypic and phenotypic disease networks, using a large statewide cohort of individuals (100, 000+ from California, USA) with linked clinical and genotypic information, the Genetic Epidemiology Research on Adult Health and Aging (GERA). By comparing their phenotypic and genotypic networks, we try to disentangle the epigenetic component of disease comorbidity.

Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms.

BACKGROUND: Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others. OBJECTIVES: 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression. DESIGN: Randomized controlled trial. SETTING: Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University). PARTICIPANTS: 396 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). INTERVENTION: 12-month PA intervention compared to an education control. MEASUREMENTS: Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales. RESULTS: Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms. CONCLUSIONS: Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.

Psychological influences predict recovery following exercise induced shoulder pain.

Predicting recovery following muscle injury can be difficult because it involves consideration of multiple factors. Our objective was to determine if psychological factors, sex, and peak pain and disability ratings could be predictive of delayed recovery following induced muscle injury. Healthy untrained volunteers (n=126; M:F 51:75) underwent a concentric/eccentric isokinetic exercise protocol on their dominant shoulder to induce fatigue, with individuals who reported pain (>0/10) at 96 h being classified as "not recovered". Individuals experiencing pain at 48 h were more likely not to be recovered (O.R.=1.62, p<0.001). Additionally, individuals with higher scores in pain catastrophizing at 48 h were more likely to experience pain at 96 h (O.R.=1.06, p<0.001). Pain duration (in days) was associated with pain scores at 48 h (ß=0.385, p<0.001) and baseline anxiety (ß=0.220, p=0.007). Fear of movement/re-injury at 96 h was found to be associated with pain catastrophizing at 48 h (ß=0.537, p<0.001) and baseline levels of fear of pain (ß=0.217, p=0.004). This study provides preliminary evidence that higher pain levels and pain catastrophizing following acute muscle injury are associated with poor recovery, higher fear of movement/re-injury and longer pain duration.

Direct effects of leisure-time physical activity on walking speed.

OBJECTIVE: This study quantifies the effects of leisure-time physical activity (LTPA) on walking speed independently of body composition in an elderly cohort, and in those elderly with metabolic derangements due to age, diabetes, and cardiovascular disease (CVD). METHODS: 1655 community-dwelling women and men >55 years were measured for body composition (lean mass : fat mass ratio, LNFAT) , based on estimated bioelectric impedance by using population-specific prediction equations derived from dual-energy x-ray absorptiometry. In addition to LNFAT, LTPA, diabetes, CVD, walking speed, and other covariates were measured biannually over an 8-year period. LTPA was categorized as <22.5 Mets/week, ≥ 22.5 Mets/week, based on public-health recommended guidelines, and LNFAT was dichotomized based on its sex-specific median. Direct effects of high vs. low LTPA on walking speed were estimated for fixed levels of LNFAT, which represented an intermediary variable in the analysis. Stratified estimates of effects were obtained using subject status (e.g., age≥75 years, diabetes, CVD) at each visit. RESULTS: Walking speed was significantly greater (0.74, 0.75 m/s in women and men, respectively) if subjects experienced LTPA ≥22.5 Mets/week and > median LNFAT, compared with <22.5 Mets/week and ≤ median LNFAT (0.68, 0.69 m/s). While direct effects of LTPA contributed to higher walking speed, none were significant in the overall, nor the stratified groups of subjects, of either sex. CONCLUSIONS: Walking speed increases with greater LTPA and LNFAT in the elderly, but there was no evidence to indicate that walking speed increases from LTPA independently of body composition and the metabolic processes it represents.

Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US Task Force recommendations.

An international task force of academic and industry leaders in sarcopenia research met on December 5, 2012 in Orlando, Florida to develop guidelines for designing and executing randomized clinical trials of sarcopenia treatments. The Task Force reviewed results from previous trials in related disease areas to extract lessons relevant to future sarcopenia trials, including practical issues regarding the design and conduct of trials in elderly populations, the definition of appropriate target populations, and the selection of screening tools, outcome measures, and biomarkers. They discussed regulatory issues, the challenges posed by trials of different types of interventions, and the need for standardization and harmonization. The Task Force concluded with recommendations for advancing the field toward better clinical trials.

WHAT WE HAVE LEARNED FROM EXERCISE AND LIFESTYLE TRIALS TO ALLEVIATE MOBILITY IMPAIRMENT IN OLDER ADULTS.

Enhancement of cardiovascular and muscular fitness through exercise and lifestyle interventions is critical to in alleviating mobility impairment in older adults. In this review article, we discuss the current knowledge-base surrounding mobility improvements in seniors following behavioral interventions that use lifestyle modifications involving physical activity and dietary interventions.

Relative safety of 4 weeks of blood flow-restricted resistance exercise in young, healthy adults.

This study evaluated the effect of 4 weeks of low-load resistance exercise with blood flow restriction (BFRE) on increasing strength in comparison with high-load resistance exercise (HLE), and assessed changes in blood, vascular and neural function. Healthy adults performed leg extension BFRE or HLE 3 days/week at 30% and 80% of strength, respectively. During BFRE, a cuff on the upper leg was inflated to 30% above systolic blood pressure. Strength, pulse-wave velocity (PWV), ankle-brachial index (ABI), prothrombin time (PT) and nerve conduction (NC) were measured before and after training. Markers of coagulation (fibrinogen and D-dimer), fibrinolysis [tissue plasminogen activator (tPA)] and inflammation [high sensitivity C-reactive protein (hsCRP)] were measured in response to the first and last exercise bouts. Strength increased 8% with BFRE and 13% with HLE (P<0.01). No changes in PWV, ABI, PT or NC were observed following training for either group (P>0.05). tPA antigen increased 30-40% immediately following acute bouts of BFRE and HLE (P=0.01). No changes were observed in fibrinogen, D-dimer or hsCRP (P>0.05). These findings indicate that both protocols increase the strength without altering nerve or vascular function, and that a single bout of both protocols increases fibrinolytic activity without altering selected markers of coagulation or inflammation in healthy individuals.

European ancestry and resting metabolic rate in older African Americans.

BACKGROUND/OBJECTIVES: Resting metabolic rate (RMR) contributes 60-80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through single nucleotide polymorphism (SNP) analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans. SUBJECTS/METHODS: RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7±3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex. RESULTS: Mean EA was 23.8±16% (range: 0.1-70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (P=0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry, with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association. CONCLUSIONS: EA in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.

Myogenic and proteolytic mRNA expression following blood flow restricted exercise.

AIM: Resistance exercise performed at low loads (20-30% of maximal strength) with blood flow restriction (BFR) acutely increases protein synthesis and induces hypertrophy when performed chronically. We investigated myogenic and proteolytic mRNA expression 8 h following an acute bout of knee extension exercise. METHODS: Fifteen subjects (22.8 ± 3.7 years, eight men and seven women) were randomized to two exercise conditions: BFR or control exercise. All participants performed four sets of exercise (30, 15, 15 and 15 repetitions) at 20% of maximal strength. Persons in the BFR group had a cuff placed on the upper thigh inflated to 1.5 times brachial systolic blood pressure (cuff pressure range: 135-186 mmHg). Muscle biopsies from the vastus lateralis were excised 24 h before and 8 h following the exercise. RESULTS: RT-PCR analysis demonstrated no change in myogenic gene expression (insulin-like growth factor-1, MyoD, myogenin, myostatin - a negative regulator) with either exercise condition (P > 0.123). However, BFR exercise downregulated mRNA expression in transcripts associated with proteolytic pathways (FOXO3A, Atrogin-1 and MuRF-1) with no change in the control exercise condition. Specifically, median mRNA expression of FOXO3A decreased by 1.92-fold (P = 0.01), Atrogin-1 by 2.10-fold (P = 0.01) and MuRF-1 by 2.44-fold (P = 0.01). CONCLUSION: These data are consistent with the downregulation of proteolytic transcripts observed following high-load resistance exercise. In summary, myogenic genes are unchanged and proteolytic genes associated with muscle remodelling are reduced 8 h following low-load BFR exercise.

Sarcopenia: clinical evaluation, biological markers and other evaluation tools.

Sarcopenia is characterized by a lower skeletal muscle quantity, higher fat accumulation in the muscle, lower muscle strength, and lower physical performance. The most commonly used, low cost and accessible methods to assess skeletal muscle mass include dual energy X-ray absorptiometry (DEXA), anthropometry and bioelectrical impedance analysis (BIA). Magnetic resonance imaging (MRI), computerized tomography (CT) and creatinine excretion are the most specific golden standards for assessing muscle mass or cross sectional muscle area. Other available measures include peripheral quantitative computerized tomography (pQCT), ultrasound and neutron activation. Skeletal muscle strength is another important component for the assessment of sarcopenia and muscle quality. Several methods are available for the measurement of muscle strength which include simple dynamometers to measure isometric strength and the most complex isokinetic strength measures of power and torque. Standardized physical performance measures complement the measures of muscle mass for the assessment of sarcopenia. A clinical definition of sarcopenia ought to use methods of assessment that are valid, reliable, specific to skeletal muscle, predictive of future health events, non-invasive, practical, low cost and widely accessible.