The lower extremities are important to performing physical activities of daily life. This study investigated lower extremity tissue composition, i.e. muscle and fat volumes, in young and older adults and the relative importance of individual tissue compartments to the physical function of older adults. A total of 43 older (age 78.3 ± 5.6 yr) and 20 younger (age 23.8 ± 3.9 yr) healthy men and women participated in the study. Older participants were further classified as either high- (HF) or low-functioning (LF) according to the Short Physical Performance Battery (SPPB). Magnetic resonance images were used to determine the volumes of skeletal muscle, subcutaneous fat (SAT), and intermuscular fat (IMAT) in the thigh (femoral) and calf (tibiofibular) regions. After adjusting for the sex of participants, younger participants had more femoral muscle mass than older adults (p < 0.001 for between group differences) as well as less femoral IMAT (p = 0.008) and tibiofibular IMAT (p < 0.001). Femoral muscle was the only tissue compartment demonstrating a significant difference between the two older groups, with HF participants having 31% more femoral muscle mass than LF participants (mean difference = 103.0 ± 34.0 cm3; p = 0.011). In subsequent multiple regression models including tissue compartments and demographic confounders, femoral muscle was the primary compartment associated with both SPPB score (r2 = 0.264, p= 0.001) and 4-meter gait speed (r2 = 0.187, p= 0.007). These data suggest that aging affects all lower extremity compartments, but femoral muscle mass is the major compartment associated with physical function in older adults.

Background.

Muscle weakness and obesity are two significant threats to mobility facing the increasing number of older adults. To date, there are no studies that have examined the association of strength and body mass index (BMI) on event rates on a widely used performance measure of major mobility disability.

Methods.

This study was a secondary analysis of a randomized controlled trial in which sedentary functionally limited participants (70–89 years, Short Physical Performance Battery ≤ 9) who were able to complete a 400-m walk test at baseline were randomized to a physical activity or health education intervention and reassessed for major mobility disability every 6 months for up to 18 months. We evaluated whether baseline grip strength and BMI predicted failure to complete the 400-m walk test in 15 minutes or less (major mobility disability).

Results.

Among N = 406 participants with baseline measures, lower grip strength was associated with an increased risk for developing major mobility disability, with and without covariate adjustment (p < .01): The hazard ratio (95% confidence interval) for the lowest versus high sex-specific quartile of grip strength was 6.11 (2.24–16.66). We observed a U-shaped relationship between baseline BMI and the risk of developing major mobility disability, such that the risk for participants with a BMI of 25–29 kg/m2 was approximately half that of participants with BMI less than 25 or 30 kg/m2 or more (p = .04 in fully adjusted analyses).

Conclusions.

Our data highlight the importance of muscle weakness, low BMI, and obesity as risk factors for major mobility disability in older adults. Being overweight may be protective for major mobility disability.

Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject.

Abstract

Obese older adults are particularly susceptible to sarcopenia and have a higher prevalence of disability than their peers of normal weight. Interventions to improve body composition in late life are crucial to maintaining independence. The main mechanisms underlying sarcopenia have not been determined conclusively, but chronic inflammation, apoptosis, and impaired mitochondrial function are believed to play important roles. It has yet to be determined whether impaired cellular quality control mechanisms contribute to this process. The objective of this study was to assess the effects of a 6-month weight loss program combined with moderate-intensity exercise on the cellular quality control mechanisms autophagy and ubiquitin-proteasome, as well as on inflammation, apoptosis, and mitochondrial function, in the skeletal muscle of older obese women. The intervention resulted in significant weight loss (8.0 ± 3.9 % vs. 0.4 ± 3.1% of baseline weight, p = 0.002) and improvements in walking speed (reduced time to walk 400 meters, − 20.4 ± 16% vs. − 2.5 ± 12%, p = 0.03). In the intervention group, we observed a three-fold increase in messenger RNA (mRNA) levels of the autophagy regulators LC3B, Atg7, and lysosome-associated membrane protein-2 (LAMP-2) compared to controls. Changes in mRNA levels of FoxO3A and its targets MuRF1, MAFBx, and BNIP3 were on average seven-fold higher in the intervention group compared to controls, but these differences were not statistically significant. Tumor necrosis factor-α (TNF-α) mRNA levels were elevated after the intervention, but we did not detect significant changes in the downstream apoptosis markers caspase 8 and 3. Mitochondrial biogenesis markers (PGC1α and TFAm) were increased by the intervention, but this was not accompanied by significant changes in mitochondrial complex content and activity. In conclusion, although exploratory in nature, this study is among the first to report the stimulation of cellular quality control mechanisms elicited by a weight loss and exercise program in older obese women.

Background

Preclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.

Methodology/Principal Findings

Community-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R2 = 0.78; Q2 = 0.61) as well as gait speed (R2 = 0.81; Q2 = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).

Conclusions/Significance

Data from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons.

Background

A growing body of evidence has consistently shown a correlation between obesity and chronic sub-clinical inflammation. Several studies have suggested that measures of body fat distribution, rather than overall adiposity, may be more closely associated with inflammation level.

Objective

To investigate the relationship between levels of inflammatory markers and specific measures of abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat of older white and black adults.

Design

Data of 2,651 black and white men and women aged 70-79 participating in the Health, Aging and Body Composition (Health ABC) study were used. Levels of the inflammatory markers, IL-6, CRP, and TNF-α were obtained from blood samples. The areas of abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were quantified on CT images. Linear regression analysis was used to evaluate the cross-sectional relationship between each body composition measure and serum levels of inflammatory markers in the four race/gender groups.

Results

Abdominal visceral adiposity was most consistently associated with significantly higher IL-6 and CRP levels in all race/gender groups (p<0.05). Thigh intermuscular fat had an inconsistent but significant association with inflammation, and there was a trend toward lower inflammation level with increasing thigh subcutaneous fat in white and black women.

Conclusions

Despite the previously established differences in abdominal fat distribution across gender and race, visceral fat remained a significant predictor of inflammatory marker level across all four subgroups examined.

Purpose

To determine the effects of a 12-month physical activity intervention on inflammatory biomarkers in elderly men and women.

Methods

424 elderly (aged 70–89 years), nondisabled, community-dwelling men and women at risk for physical disability were enrolled in a multicenter, single-blind, randomized controlled-trial. Participants were randomized to participate in either a 12-month moderate-intensity physical activity (PA) intervention or a successful aging (SA) health education intervention. Biomarkers of inflammation (IL-6sR, IL-1sRII, sTNFRI, sTNFRII, IL-8, IL-15, adiponectin, IL-1ra, IL-2sRα, and TNF-α) were measured at baseline, 6 and 12 months.

Results

A baseline blood sample was successfully collected from 368 participants. After adjustment for gender, clinic site, diabetes status, and baseline outcome measure, IL-8 was the only inflammatory biomarker affected by the PA intervention (p=0.03). The adjusted mean IL-8 at month 12 was 9.9% (0.87 pg/mL) lower in the PA compared to the SA group. Secondary interaction analyses between baseline biomarker status and treatment showed one significant interaction (p=0.02) such that the PA intervention reduced IL-15 concentrations in participants with a baseline IL-15 above the median value of 1.67 pg/mL. However, these associations were no longer significant after consideration for multiple comparisons.

Conclusions

Overall, this study does not provide definitive evidence for an effect of regular exercise for altering systemic concentrations of the measured inflammatory biomarkers in older adults.

A primary focus of longevity research is to identify prognostic risk factors that can be mediated by early treatment efforts. To date, much of this work has focused on understanding the biological processes that may contribute to aging process and age-related disease conditions. Although such processes are undoubtedly important, no current biological intervention aimed at increasing health and lifespan exists. Interestingly, a close relationship between mobility performance and the aging process has been documented in older adults. For example, recent studies have identified functional status, as assessed by walking speed, as a strong predictor of major health outcomes, including mortality, in older adults. This paper aims to describe the relationship between the comorbidities related to decreased health and lifespan and mobility function in obese, older adults. Concurrently, lifestyle interventions, including diet and exercise, are described as a means to improve mobility function and thereby limit the functional limitations associated with increased mortality.

The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a pro-thrombotic imbalance in the fibrinolysis homeostasis has been hypothesized at the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the resulting of the interactions among multiple plasminogen activators and inhibitors constituing the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen. In this review, current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker which may become a biological parameter to be growingly considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the next future.

Background.

As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking. A Phase 3 randomized controlled trial is needed to fill this evidence gap.

Methods.

The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled trial designed to compare a supervised moderate-intensity physical activity program with a successful aging health education program in 1,600 sedentary older persons followed for an average of 2.7 years.

Results.

LIFE's primary outcome is major mobility disability, defined as the inability to walk 400 m. Secondary outcomes include cognitive function, serious fall injuries, persistent mobility disability, the combined outcome of major mobility disability or death, disability in activities of daily living, and cost-effectiveness.

Conclusions.

Results of this study are expected to have important public health implications for the large and growing population of older sedentary men and women.

Background:

Obesity and a sedentary lifestyle are associated with physical impairments and biologic changes in older adults. Weight loss combined with exercise may reduce inflammation and improve physical functioning in overweight, sedentary, older adults. This study tested whether a weight loss program combined with moderate exercise could improve physical function in obese, older adult women.

Methods:

Participants (N = 34) were generally healthy, obese, older adult women (age range 55–79 years) with mild to moderate physical impairments (ie, functional limitations). Participants were randomly assigned to one of two groups for 24 weeks: (i) weight loss plus exercise (WL+E; n = 17; mean age = 63.7 years [4.5]) or (ii) educational control (n = 17; mean age = 63.7 [6.7]). In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions within their community each week. During exercise sessions, participants engaged in brisk walking and lower-body resistance training of moderate intensity. Participants in the educational control group attended monthly health education lectures on topics relevant to older adults. Outcomes were: (i) body weight, (ii) walking speed (assessed by 400-meter walk test), (iii) the Short Physical Performance Battery (SPPB), and (iv) knee extension isokinetic strength.

Results:

Participants randomized to the WL+E group lost significantly more weight than participants in the educational control group (5.95 [0.992] vs 0.23 [0.99] kg; P < 0.01). Additionally, the walking speed of participants in the WL+E group significantly increased compared with that of the control group (reduction in time on the 400-meter walk test = 44 seconds; P < 0.05). Scores on the SPPB improved in both the intervention and educational control groups from pre- to post-test (P < 0.05), with significant differences between groups (P = 0.02). Knee extension strength was maintained in both groups.

Conclusion:

Our findings suggest that a lifestyle-based weight loss program consisting of moderate caloric restriction plus moderate exercise can produce significant weight loss and improve physical function while maintaining muscle strength in obese, older adult women with mild to moderate physical impairments.

Background.

Short-term adherence to physical activity (PA) in older adults improves psychomotor processing abilities and is associated with greater brain activation. It is not known whether these associations are also significant for longer-term adherence to moderate-intensity activities.

Methods.

We measured the cross-sectional association of regular walking with brain activation while performing the digit symbol substitution test (DSST). Participants of the lifestyle interventions and independence for elders—pilot study were examined 2 years after completing a 1-year treatment, consisting of either PA or education in successful aging (SA). Data were obtained from 20 PA participants who reported having remained active for 2 years after the end of the treatment and from 10 SA participants who reported having remained sedentary during the same period (mean age: 81.5 and 80.8 years). Complete brain activation and behavioral data were available for 17 PA and 10 SA participants.

Results.

Two years after the formal intervention had ended, the PA group engaged in more minutes of moderate activity and had significantly greater DSST score and higher brain activation within regions important for processing speed (left dorsolateral prefrontal, posterior parietal, and anterior cingulate cortices). Associations were independent of self-reported health, blood pressure, cognition, medication records, gray matter atrophy, and white matter hyperintensities.

Conclusions.

Persistent engagement in PA may have beneficial effects on psychomotor processing speed and brain activation, even for moderate levels and even when started late in life. Future studies are warranted to assess whether these beneficial effects are explained by delayed neuronal degeneration and/or new neurogenesis.

We examined the costs of a physical activity (PA) and an educational comparison intervention. 424 older adults at risk for mobility disability were randomly assigned to either condition. The PA program consisted of center-based exercise sessions 3× weekly for 8 weeks, 2× weekly for weeks 9 to 24 and weekly behavioral counseling for 10 weeks. Optional sessions were offered during maintenance weeks (25–52). The comparison intervention consisted of weekly education meetings for 24 weeks, and then monthly for 6 months. Cost analyses were conducted from the “payer’s” perspective, with a 1-year time horizon. Intervention costs were estimated by tracking personnel activities and materials used for each intervention and multiplying by national unit cost averages. The average cost/participant was $1134 and $175 for the PA and the comparison interventions, respectively. A preliminary cost/effectiveness analysis gauged the cost/disability avoided to be $28,206. Costs for this PA program for older adults are comparable to those of other PA interventions. The results are preliminary and a longer study is required to fully assess the costs and health benefits of these interventions.

Background

The authors sought to evaluate the acceptability and feasibility of maximal fitness testing in sedentary older individuals at risk for mobility disability.

Methods

Maximal cycle-ergometer testing was performed at baseline and 6 and 12 months later in a subset of LIFE-P study participants at the Cooper Institute site. The mean age of the 20 participants (80% female) tested was 74.7 ± 3.4 years. The following criteria were used to determine whether participants achieved maximal effort: respiratory-exchange ratio (RER) ≥1.1, heart rate within 10 beats/min of the maximal level predicted by age, and rating of perceived exertion (RPE) >17.

Results

Participants’ mean peak VO2 was 12.1 (3.7) mL · kg–1 · min–1. At baseline testing, only 20% of participants attained an RER ≥1.10, only 35% achieved a peak heart rate within 10 beats of their age-predicted maximum, and 18% had an RPE of >17. Subsequent testing at 6 and 12 months produced similar results.

Conclusions

In this pilot study of sedentary older persons at risk for mobility disability, very few participants were able to achieve maximal effort during graded cycle-ergometer testing.

Objectives

Weight change may be considered an effect of depression. In turn, depression may follow weight change. Deteriorations in health may mediate these associations. The objective was to examine reciprocal associations between depressed mood and weight change, and the potentially mediating role of deteriorations in health (interim hospitalizations and incident mobility imitation) in these associations.

Design

Prospective observational cohort study

Settings

Memphis, Tennessee and Pittsburgh, Pennsylvania

Participants

2406 black and white men and women, aged 70–79 participating in the Health, Aging and Body composition (Health ABC) study.

Measurements

Depressed mood at baseline (T1) and 3-year follow-up (T4) was measured with the CES-D scale. Three weight change groups (T1–T4) were created: loss (≥5% loss), stable (within ±5% loss or gain), and weight gain (≥5% gain).

Results

At T1 and T4, respectively 4.4% and 9.5% of the analysis sample had depressed mood. T1 depressed mood was associated with weight gain over the 3-year period (OR:1.91; 95%CI:1.13–3.22). Weight loss over the 3-year period was associated with T4 depressed mood (OR:1.51; 95%CI:1.05–2.16). Accounting for deteriorations in health in the reciprocal associations between weight change and depressed mood reduced effect sizes between 16–27%.

Conclusions

In this study, depressed mood predicted weight gain over three years, while weight loss over three years predicted depressed mood. These associations were partly mediated through deteriorations in health. Implications for clinical practice and prevention include increased awareness that depressed mood can cause weight change, but can also be preceded by deteriorations in health and weight change.

Context

Older adults responding to executive control function (ECF) tasks show greater brain activation on functional MRI (fMRI). It is not clear whether greater fMRI activation indicates a strategy to compensate for underlying brain structural abnormalities while maintaining higher performance.

Objective

To identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities.

Design

Cross-sectional analysis. Main variables of interest: fMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), volume of white matter hyperintensities and of total brain atrophy.

Setting

Cohort of community-dwelling older adults.

Participants

Data were obtained on 25 older adults (20 women, 81 years mean age).

Outcome Measure

Accuracy (number of correct response / total number of responses) while performing the Digit Symbol Substitution Test.

Results

Greater accuracy was significantly associated with greater peak fMRI activation, from ECF regions, including left middle frontal gyrus and right posterior parietal cortex. Greater WMH was associated with lower activation within accuracy-related regions. The interaction of accuracy by white matter hyperintensities volume was significant within the left posterior parietal region. Specifically, the correlation of white matter hyperintensities volume with fMRI activation varied as a function of accuracy and it was positive for greater accuracy. Associations with brain atrophy were not significant.

Conclusions

Recruitment of additional areas and overall greater brain activation in older adults is associated with higher performance. Posterior parietal activation may be particularly important to maintain higher accuracy in the presence of underlying brain connectivity structural abnormalities.

Background: the existence of a relationship among inflammation, high-density lipoprotein cholesterol (HDL-C) and physical function has been suggested.

Objective: the aim of the study is to investigate the possible interaction of HDL-C on inflammation and physical function.

Design: cross-sectional study.

Setting: town of Tuscania (Italy).

Subjects: all the 329 community-dwelling older persons aged ≥75 years (mean age 79.8 ± 5.2 years, women 56.2%).

Methods: HDL-C, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. Activities of daily living (ADL), instrumental ADL (IADL) and 4-m walking speed were assessed. Linear regression models were performed.

Results: given the multiple significant interactions, models were stratified according to HDL-C concentrations. In participants with normal HDL-C concentrations, only IL-6 showed a significant association with IADL (β = −0.439, SE = 0.176, P = 0.01). In participants with low HDL-C concentrations, all three inflammatory biomarkers were significantly associated with 4-m walking speed and IADL. IL-6 was also significantly associated with ADL (β = −0.755, SE = 0.259, P = 0.006), whereas borderline significances were reported for CRP and ESR.

Conclusions: the association between inflammation and physical function is particularly enhanced in elders with low HDL-C concentrations. Though HDL-C may merely act as a wellbeing index, HDL-C concentrations should be considered in studies evaluating inflammation and physical function.

Objectives

Aim of the present study is to evaluate whether an ACE inhibitor intervention is able to significantly improve physical performance and muscle strength in a sample of older persons.

Design

Double-blind, cross-over, randomized, placebo-controlled trial.

Setting

The Trail of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.

Participants

Two hundred fiftyseven subjects aged 55 years and older with high cardiovascular risk profile.

Intervention

Six month of fosinopril use versus placebo.

Measurements

The Short Physical Performance Battery score (rescaled to obtain a continuous variable ranging from 0 to 3 points), and the hand grip strength were measured at the baseline visit, and after 6 and 12 months of follow-up. Paired t-test analyses were performed to compare results of physical function measures after ACE inhibition and placebo interventions.

Results

Mean age of the sample population was 65.97 (standard deviation 7.41) years old. No statistically significant difference was found at the Short Physical Performance Battery (p=0.23) and hand grip strength (p=0.57) results after ACE inhibition (2.113, standard deviation [SD] 0.284; and 37.044 kg, SD 12.993 kg, respectively) compared to placebo (2.096, SD 0.298; and 36.898 kg, SD 13.178 kg, respectively). No significant effects from ACE inhibition were also found when the three subtests composing the Short Physical Performance Battery (i.e., 4-meter walking speed, balance, and chair stand tests) were separately analyzed. Consistent negative results were obtained after analyses were restricted to participants showing the highest compliance to treatment and/or receiving the maximum fosinopril dosage.

Conclusion

No significant modifications in physical performance and muscle strength were reported after 6 months of fosinopril use in older persons with high cardiovascular risk profile. Given these negative findings, it is possible that the beneficial effects of ACE inhibitors on physical function might be due to the activation of a virtuous cycle determined by an improved cardiovascular system. Further specifically designed studies are needed to confirm our findings, and expand them to different populations and ACE inhibitors. If our findings will be confirmed, the extra-cardiovascular properties of ACE inhibitors in older persons might be substantially resized.

Background

There is growing evidence that higher levels of inflammatory markers are associated with physical decline in older persons, possibly through the catabolic effects of inflammatory markers on muscle. The aim of this study was to investigate the association between serum levels of inflammatory markers and loss of muscle mass and strength in older persons.

Methods

Using data on 2,177 men and women in the Health, Aging, and Body Composition Study, we examined 5-year change in thigh muscle area estimated by computed tomography and grip and knee extensor strength in relation to serum levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-alpha (TNF-α), and soluble receptors (measured in a subsample) at baseline.

Results

Higher levels of inflammatory markers were generally associated with greater 5-year decline in thigh muscle area. Most associations, with the exception of soluble receptors, were attenuated by adjustment for 5-year change in weight. Higher TNF-α and interleukin-6 soluble receptor levels remained associated with greater decline in grip strength in men. Analyses in a subgroup of weight-stable persons showed that higher levels of TNF-α and its soluble receptors were associated with 5-year decline in thigh muscle area and that higher levels of TNF-α were associated with decline in grip strength.

Conclusions

TNF-α and its soluble receptors showed the most consistent associations with decline in muscle mass and strength. The results suggest a weight-associated pathway for inflammation in sarcopenia.

The purpose of this study was to conduct a pilot clinical trial to test the feasibility and efficacy of an exercise program and anti-depressant treatment compared with usual care in improving the emotional and physical functioning of older adults with minor depression. Participants were 37 older adults with minor depression who were randomized to exercise, sertraline, or usual care; 32 participants completed the 16 week study. Outcomes included measures of both emotional (clinician and self-report) and physical (observed and self-report) functioning. There were trends for the superiority of the exercise and sertraline conditions over usual care in improving SF-36 mental health scores and clinician-rated depression scores. Individuals in the exercise condition showed greater improvements in physical functioning than individuals in the usual care condition. Both sertraline and exercise show promise as treatments for late-life minor depression. However, exercise has the added benefit of improving physical functioning as well.

Background

Cognitive impairment is an important contributor to disability. Limited clinical trial evidence exists regarding the impact of physical exercise on cognitive function (CF). We report results of a pilot study to provide estimates of the relative impact of physical activity (PA) on 1-year changes in cognitive outcomes and to characterize relationships between changes in mobility disability and changes in cognition in older adults at increased risk for disability.

Methods

Sedentary persons (102) at increased risk for disability (aged 70–89 years) were randomized to moderate-intensity PA or health education. Participants were administered the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), modified Stroop test, and Modified Mini-Mental State Examination at baseline and 1 year.

Results

Group differences were not significant but improvements in cognitive scores were associated with improvements in physical function. Specifically, the DSST significantly correlated with change in the Short Physical Performance Battery score (r = .38, p = .0002), in chair stand score (r = .26, p = .012), in balance score (r = .21, p = .046), and in 400-m gait speed (r = .15, p = .147). Change recall on the RAVLT and in the Stroop test was also positively correlated with changes in chair stand and balance, respectively.

Conclusions

These results provide further support for the benefits of exercise on CF in older adults. An adequately powered clinical trial of PA involving older adults at increased risk for cognitive disability is needed to expand the indications for prescribing exercise for prevention of decline in brain function.

Background

Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status.

Methods

We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and anthropometric measures.

Results

Higher levels of CRP and IL-6, but not TNF-α, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results.

Conclusions

Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.

Background

Sarcopenia, the age-related loss of muscle mass, may not be an isolated process but is associated with an increase in fat mass. The aim of this study was to estimate the mortality risk of sarcopenia in the presence or absence of obesity.

Methods

Data are from 934 participants aged 65 years or older, enrolled in the “Invecchiare in Chianti” study, and followed for 6 years. At baseline, a peripheral quantitative computerized tomography (pQCT) scan was performed on all participants to evaluate the muscle density, and the muscular and fat cross-sectional areas of the calf. Walking speed was measured on a 7-m track. Cox proportional hazard models were performed to estimate the association of pQCT measures (per 1 standard deviation increase) with mortality.

Results

Unadjusted analyses showed significant associations of muscle density (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.69–0.88), muscle area (HR 0.75, 95% CI 0.66–0.86), and fat area (HR 0.82, 95% CI 0.73–0.92) with mortality. After adjustment for potential confounders, no body composition parameter was significantly associated with mortality. Walking speed (used as a reference measure to verify whether the negative results were due to peculiarities of the study sample) confirmed its well-established association with mortality risk (HR 0.73, 95% CI 0.60–0.88). These results did not change after the analyses were stratified according to sarcopenia and body mass index groups, and restricted to participants with frailty or a high inflammatory profile.

Conclusions

Calf skeletal muscle and fat mass are not significant risk factors for mortality in community-dwelling older adults. Walking speed confirmed to be a powerful predictor of health-related events.

OBJECTIVES

To examine the association of stopping to rest during a 400 meter usual-pace walk test (400-MWT) with incident mobility disability in older persons with functional limitations.

DESIGN

Prospective cohort study

SETTING

Community-based

PARTICIPANTS

Four hundred twenty-four participants of the Lifestyle Intervention and Independence for Elders Pilot (LIFE-P) Study aged 70–89 years, having functional limitation (summary score =9 on the Short Physical Performance Battery (SPPB)), and being able to complete the 400-MWT within 15 minutes.

MEASUREMENTS

Rest stops during the 400-MWT were recorded. The onset of mobility disability, defined as being unable to complete the 400-MWT or taking more than 15 minutes to do so, was recorded at months 6 and 12.

RESULTS

Fifty-four (12.7%) participants rested during the 400-MWT at baseline, of whom 37.7% experienced mobility disability during follow-up versus 8.6% of those not stopping to rest. Performing any rest stop was strongly associated with incident mobility disability at follow-up (odds ratio (OR) = 5.4, 95% confidence interval (CI) = 2.7–10.9) after adjustment for age, gender, and clinic site. This association was diminished, but remained statistically significant, after further adjusting for SPPB and the time to complete the 400-MWT simultaneously (OR = 2.6, 95%CI = 1.2–5.9).

CONCLUSION

Stopping to rest during the 400-MWT is strongly associated with incident mobility disability in non-disabled older persons with functional limitations. Given the prognostic value, rest stops should be recorded as part of the standard assessment protocol for the 400-MWT.