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1.  Intervening on spontaneous physical activity to prevent weight regain in older adults: Design of a randomized, clinical trial 
Contemporary clinical trials  2011;33(2):450-455.
There is a need to identify evidenced-based obesity treatments that are effective in maintaining lost weight. Weight loss results in reductions in energy expenditure, including spontaneous physical activity (SPA) which is defined as energy expenditure resulting primarily from unstructured mobility-related activities that occur during daily life. To date, there is little research, especially randomized, controlled trials, testing strategies that can be adopted and sustained to prevent declines in SPA that occur with weight loss. Self-monitoring is a successful behavioral strategy to facilitate behavior change, so a provocative question is whether monitoring SPA-related energy expenditure would override these reductions in SPA, and slow weight regain. This study is a randomized trial in older, obese men and women designed to test the hypothesis that adding a self-regulatory intervention (SRI), focused around self-monitoring of SPA, to a weight loss intervention will result in less weight and fat mass regain following weight loss than a comparable intervention that lacks this self-regulatory behavioral strategy. Participants (n=72) are randomized to a 5-month weight loss intervention with or without the addition of a behavioral component that includes an innovative approach to promoting increased SPA. Both groups then transition to self-selected diet and exercise behavior for a 5-month follow-up. Throughout the 10-month period, the SRI group is provided with an intervention designed to promote a SPA level that is equal to or greater than each individual's baseline SPA level, allowing us to isolate the effects of the SPA self-regulatory intervention component on weight and fat mass regain.
PMCID: PMC4318512  PMID: 22155531
Obesity; Weight loss maintenance; Self-monitoring; Self-regulation; Physical activity
2.  The Independent and Combined Effects of Physical Activity and Weight Loss on Inflammatory Biomarkers in Overweight and Obese Older Adults 
To determine the independent effect of long-term physical activity (PA) and the combined effects of long-term PA and weight loss (WL) on inflammation in overweight and obese older adults.
18-month randomized, controlled trial.
This study was conducted within the community infrastructure of Cooperative Extension Centers.
288 older (60–79 years), overweight and obese (BMI > 28 kg/m2) community dwelling men and women at risk for cardiovascular disease (CVD).
PA + WL (n=98), PA only (n=97), or successful aging (SA) health education (n=93) intervention.
Biomarkers of inflammation (adiponectin, leptin, hsIL-6, IL-6sR, IL-8, and sTNFR1) were measured at baseline, 6 and 18 months.
After adjustment for baseline biomarker, wave, gender and visit, both leptin and hsIL-6 showed a significant intervention effect. Specifically, leptin (ng/ml) was significantly lower in the PA+WL group compared to PA or SA [21.3 (95% CI: 19.7–22.9) vs. 29.3 (26.9–31.8) and 30.3 (27.9–32.8), respectively; both p<0.01], and hsIL-6 (pg/mL) was also significantly lower in the PA+WL group compared to PA or SA [2.1 (95% CI: 1.9–2.3) vs. 2.5 (2.3–2.7) and 2.4 (2.2–2.6), respectively; both p<0.05].
Addition of dietary-induced WL to PA reduced leptin and hsIL-6 compared to PA alone and to a SA intervention in older adults at risk for CVD. Results suggest that WL, rather than increased PA, is the lifestyle factor primarily responsible for improvement in the inflammatory profile.
PMCID: PMC3714323  PMID: 23772804
physical activity; weight loss; inflammation; aging
3.  Regional Differences in Adipose Tissue Hormone/Cytokine Production Before and After Weight Loss in Abdominally Obese Women 
Obesity (Silver Spring, Md.)  2014;22(7):1679-1684.
To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss.
Design and Methods
Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ~2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention.
Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. The intervention resulted in significant weight loss (−10.1 ±0.7 kg, P<0.001). At baseline, gene expression of adiponectin were higher (P<0.01), and gene expression and release of IL-6 were lower (both P<0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P<0.05 to P<0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P<0.05).
A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity.
PMCID: PMC4077942  PMID: 24634403
Adipose Tissue; Hormones; Cytokines; Weight Loss; Abdominal Obesity
4.  Effect of exercise training on chronic inflammation 
Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.
PMCID: PMC3629815  PMID: 20188719
inflammation; exercise; cytokines; acute phase proteins; physical activity
5.  The Effects of a Long-Term Physical Activity Intervention on Serum Uric Acid in Older Adults at Risk for Physical Disability 
Observational studies show a relationship between elevated serum uric acid (UA) and better physical performance and muscle function. The purpose of this paper was to determine whether regular participation in an exercise intervention, known to improve physical functioning, would result in increased serum UA. For this study, 424 older adults at risk for physical disability were randomized to participate in either a 12-mo moderate-intensity physical activity (PA) or a successful aging (SA) health education intervention. UA was measured at baseline, 6, and 12 mo (n = 368, 341, and 332, respectively). Baseline UA levels were 6.03 ± 1.52 mg/dl and 5.94 ± 1.55 mg/dl in the PA and SA groups, respectively. The adjusted mean UA at month 12 was 4.8% (0.24 mg/dl) higher in the PA compared with the SA group (p = .028). Compared with a health education intervention, a 1-yr PA intervention results in a modest increase in systemic concentration of UA in older adults at risk for mobility disability.
PMCID: PMC4120269  PMID: 23295313
exercise; aging; health education
6.  Effect of an 18 month physical activity and weight loss intervention on body composition in overweight and obese older adults 
Obesity (Silver Spring, Md.)  2013;22(2):325-331.
Our primary objective was to determine the long-term effects of physical activity (PA) and weight loss (WL) on body composition in overweight/obese older adults. Secondarily, we evaluated the association between change in body mass and composition on change in several cardiometabolic risk factors and mobility.
Design and Methods
288 older (X±SD: 67.0±4.8 years), overweight/obese (BMI 32.8±3.8 kg/m2) men and women participated in this 18 month randomized, controlled trial. Treatment groups included PA+WL (n=98), PA-only (n=97), and a successful aging (SA) health education control (n=93). DXA-acquired body composition measures (total body fat and lean mass), conventional biomarkers of cardiometabolic risk, and 400-m walk time were obtained at baseline and 18 months.
Fat mass was significantly reduced from (X±SE) 36.5±8.9 kg to 31.7±9.0 kg in the PA+WL group (p<0.01), but remained unchanged from baseline in the PA-only (−0.8±3.8 kg) and SA (−0.0±3.9 kg) groups. Lean mass losses were three times greater in the PA+WL group compared to PA-only or SA groups (−2.5±2.8 kg vs. −0.7±2.2 kg or −0.8±2.4 kg, respectively; p<0.01); yet due to a larger decrease in fat mass, percent lean mass was significantly increased over baseline in the PA+WL group (2.1%±2.6%; p<0.01). Fat mass loss was primarily responsible for WL-associated improvements in cardiometabolic risk factors, while reduction in body weight, regardless of compartment, was significantly associated with improved mobility.
This 18 month PA+WL program resulted in a significant reduction in percent body fat with a concomitant increase in percent body lean mass. Shifts in body weight and composition were associated with favorable changes in clinical parameters of cardiometabolic risk and mobility. Moderate PA without WL had no effect on body composition.
PMCID: PMC3880399  PMID: 23963786
weight loss; physical activity; body composition; cardiometabolic risk; functional decline; aging
7.  Lean Mass Loss Is Associated with Low Protein Intake during Dietary-Induced Weight Loss in Postmenopausal Women 
The health and quality-of-life implications of overweight and obesity span all ages in the United States. We investigated the association between dietary protein intake and loss of lean mass during weight loss in postmenopausal women through a retrospective analysis of a 20-week randomized, controlled diet and exercise intervention in women aged 50 to 70 years. Weight loss was achieved by differing levels of caloric restriction and exercise. The diet-only group reduced caloric intake by 2,800 kcal/week, and the exercise groups reduced caloric intake by 2,400 kcal/week and expended ~400 kcal/week through aerobic exercise. Total and appendicular lean mass was measured using dual energy x-ray absorptiometry. Linear regression analysis was used to examine the association between changes in lean mass and appendicular lean mass and dietary protein intake. Average weight loss was 10.8±4.0 kg, with an average of 32% of total weight lost as lean mass. Protein intake averaged 0.62 g/kg body weight/day (range=0.47 to 0.8 g/kg body weight/day). Participants who consumed higher amounts of dietary protein lost less lean mass and appendicular lean mass r(=0.3, P=0.01 and r=0.41, P<0.001, respectively). These associations remained significant after adjusting for intervention group and body size. Therefore, inadequate protein intake during caloric restriction may be associated with adverse body-composition changes in postmenopausal women.
PMCID: PMC3665330  PMID: 18589032
8.  Relationship of physical function to vastus lateralis capillary density and metabolic enzyme activity in elderly men and women 
Background and aims
There are no data showing whether or not age-related declines in physical function are related to in vitro properties of human skeletal muscle. The purpose of this study was to determine whether physical function is independently associated with histologic and metabolic properties of skeletal muscle in elderly adults.
The study was a cross-sectional observational study of 39 sedentary, older (60–85 yrs) men and women. A needle biopsy of the vastus lateralis for assessment of muscle fiber type, fiber area, capillary density and citrate synthase and aldolase activities was performed. Physical function tests included the Short Physical Performance Battery (balance, walking speed, and chair rise time), as well as self-reported disability.
Total fiber area (R=−0.41, p=0.02), number of Type II fibers (R=−0.33, p=0.05), and aldolase activity (R=−0.54, p=0.01) were inversely related to age. Persons who reported greater difficulty with daily activities had lower capillary density (R=−0.51, p=0.03) and lower citrate synthase activity (R=−0.66, p=0.03). Walking speed was directly related to fiber area (R=0.40, p=0.02), capillary density (R=0.39, p=0.03), citrate synthase (R=0.45, p=0.03) and aldolase (R=0.55, p<0.01) activities, even after adjustment for age, BMI and disease status.
In older adults, skeletal muscle capillary density and metabolic enzymatic activity are independent predictors of lower extremity physical function.
PMCID: PMC3665340  PMID: 18852542
Capillary density; enzyme activity; physical function; skeletal muscle
9.  Resistance Training and Pioglitazone Lead to Improvements in Muscle Power During Voluntary Weight Loss in Older Adults 
The prevalence of obesity in older adults is increasing but concerns exist about the effect of weight loss on muscle function. Demonstrating that muscle strength and power are not adversely affected during “intentional” weight loss in older adults is important given the wide-ranging negative health effects of excess adiposity.
Participants (N = 88; age = 70.6 ± 3.6 years; body mass index = 32.8 ± 4.5kg/m2) were randomly assigned to one of four intervention groups: pioglitazone or placebo and resistance training (RT) or no RT, while undergoing intentional weight loss via a hypocaloric diet. Outcomes were leg press power and isometric knee extensor strength. Analysis of covariance, controlling for baseline values, compared follow-up means of power and strength according to randomized groups.
Participants lost an average of 6.6% of initial body mass, and significant declines were observed in fat mass, lean body mass, and appendicular lean body mass. Compared with women not randomized to RT, women randomized to RT had significant improvements in leg press power (p < .001) but not in knee extensor strength (p = 0.12). No significant differences between groups in change in power or strength from baseline were detected in men (both p > .25). A significant pioglitazone-by-RT interaction for leg press power was detected in women (p = .006) but not in men (p = .88).
In older overweight and obese adults, a hypocaloric weight loss intervention led to significant declines in lean body mass and appendicular lean body mass. However, in women assigned to RT, leg power significantly improved following the intervention, and muscle strength or power was not adversely effected in the other groups. Pioglitazone potentiated the effect of RT on muscle power in women but not in men; mechanisms underlying this sex effect remain to be determined.
PMCID: PMC3693600  PMID: 23292287
Obesity; Resistance training; Muscle strength; Muscle power; Voluntary weight loss.
10.  Lean Mass Loss Is Associated with Low Protein Intake during Dietary-Induced Weight Loss in Postmenopausal Women 
The health and quality-of-life implications of overweight and obesity span all ages in the United States. We investigated the association between dietary protein intake and loss of lean mass during weight loss in postmenopausal women through a retrospective analysis of a 20-week randomized, controlled diet and exercise intervention in women aged 50 to 70 years. Weight loss was achieved by differing levels of caloric restriction and exercise. The diet-only group reduced caloric intake by 2,800 kcal/week, and the exercise groups reduced caloric intake by 2,400 kcal/week and expended ~400 kcal/week through aerobic exercise. Total and appendicular lean mass was measured using dual energy x-ray absorptiometry. Linear regression analysis was used to examine the association between changes in lean mass and appendicular lean mass and dietary protein intake. Average weight loss was 10.8±4.0 kg, with an average of 32% of total weight lost as lean mass. Protein intake averaged 0.62 g/kg body weight/day (range=0.47 to 0.8 g/kg body weight/day). Participants who consumed higher amounts of dietary protein lost less lean mass and appendicular lean mass (r=0.3, P=0.01 and r=0.41, P<0.001, respectively). These associations remained significant after adjusting for intervention group and body size. Therefore, inadequate protein intake during caloric restriction may be associated with adverse body-composition changes in postmenopausal women.
PMCID: PMC3629809  PMID: 18810296
11.  Cardiometabolic Risk After Weight Loss and Subsequent Weight Regain in Overweight and Obese Postmenopausal Women 
Little is known about the effect of intentional weight loss and subsequent weight regain on cardiometabolic risk factors in older adults. The objective of this study was to determine how cardiometabolic risk factors change in the year following significant intentional weight loss in postmenopausal women, and if observed changes were affected by weight and fat regain.
Eighty, overweight and obese, older women (age = 58.8±5.1 years) were followed through a 5-month weight loss intervention and a subsequent 12-month nonintervention period. Body weight/composition and cardiometabolic risk factors (blood pressure; total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; fasting glucose and insulin; and Homeostatic Model Assessment of Insulin Resistance) were analyzed at baseline, immediately postintervention, and 6- and 12-months postintervention.
Average weight loss during the 5-month intervention was 11.4±4.1kg and 31.4% of lost weight was regained during the 12-month follow-up. On average, all risk factor variables were significantly improved with weight loss but regressed toward baseline values during the year subsequent to weight loss. Increases in total cholesterol, triglycerides, glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance during the postintervention follow-up were significantly (p < .05) associated with weight and fat mass regain. Among women who regained weight, model-adjusted total cholesterol (205.8±4.0 vs 199.7±2.9mg/dL), low-density lipoprotein cholesterol (128.4±3.4 vs 122.7±2.4mg/dL), insulin (12.6±0.7 vs 11.4±0.7mg/dL), and Homeostatic Model Assessment of Insulin Resistance (55.8±3.5 vs 50.9±3.7mg/dL) were higher at follow-up compared with baseline.
For postmenopausal women, even partial weight regain following intentional weight loss is associated with increased cardiometabolic risk. Conversely, maintenance of or continued weight loss is associated with sustained improvement in the cardiometabolic profile.
PMCID: PMC3660120  PMID: 23183902
Weight loss; Weight regain; Aging.
12.  The Role of Metabolic Syndrome, Adiposity, and Inflammation in Physical Performance in the Health ABC Study 
Metabolic syndrome (MetS) and functional limitation have been linked, but whether and how specific components of MetS and associated factors, such as inflammation, drive this relationship is unknown.
Data are from 2,822 men and women, aged 70–79 years, participating in the Health, Aging, and Body Composition (Health ABC) study and followed for 5 years. Presence of MetS at baseline was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Interleukin-6, C-reactive protein, and body fat mass were measured at baseline. Measures of physical performance, including 400-m walk time, 20-m walking speed, and the Health ABC physical performance battery (PPB) were obtained at baseline and examination years 2, 4, and 6.
A total of 1,036 (37%) individuals met criteria for MetS. MetS was associated with poorer physical performance at baseline. Effect estimates between MetS and gait speed, and components of the Health ABC PPB (standing balance and repeated sit-to-stand performance) were modestly attenuated after adjustment for inflammation. All associations were attenuated to nonsignificance after adding total body fat mass to the model. Longitudinal analyses yielded similar results. Individual MetS component analysis revealed that abdominal obesity explained the largest fraction of the variation in physical performance.
Although inflammatory biomarkers partially accounted for the relationship between MetS and aspects of physical performance, overall findings implicate adiposity as the primary factor explaining poorer physical performance in older adults with MetS.
PMCID: PMC3623483  PMID: 23109678
Metabolic syndrome; Physical function; Inflammation; Obesity.
13.  Fat Mass Loss Predicts Gain in Physical Function With Intentional Weight Loss in Older Adults 
Clinical recommendation of weight loss (WL) in older adults remains controversial, partially due to concerns regarding lean mass loss and potential loss of physical function. The purpose of this study is to determine the independent associations between changes in fat and lean mass and changes in physical function in older, overweight, and obese adults undergoing intentional WL.
Data from three randomized-controlled trials of intentional WL in older adults with similar functional outcomes (short physical performance battery and Pepper assessment tool for disability) were combined. Analyses of covariance models were used to investigate relationships between changes in weight, fat, and lean mass (acquired using dual-energy x-ray absorptiometry) and changes in physical function.
Overall loss of body weight was −7.8 ± 6.1 kg (−5.6 ± 4.1 kg and −2.7 ± 2.4 kg of fat and lean mass, respectively). In all studies combined, after adjustment for age, sex, and height, overall WL was associated with significant improvements in self-reported mobility disability (p < .01) and walking speed (p < .01). Models including change in both fat and lean mass as independent variables found only the change in fat mass to significantly predict change in mobility disability (β[fat] = 0.04; p < .01) and walking speed (β[fat] = −0.01; p < .01).
Results from this study demonstrate that loss of body weight, following intentional WL, is associated with significant improvement in self-reported mobility disability and walking speed in overweight and obese older adults. Importantly, fat mass loss was found to be a more significant predictor of change in physical function than lean mass loss.
PMCID: PMC3598365  PMID: 22503993
Physical function; Weight loss; Fat mass; Lean mass; Aging
14.  Lipopolysaccharide-Binding Protein, a Surrogate Marker of Microbial Translocation, Is Associated With Physical Function in Healthy Older Adults 
Physical function declines, and markers of inflammation increase with advancing age, even in healthy persons. Microbial translocation (MT) is the systemic exposure to mucosal surface microbes/microbial products without overt bacteremia and has been described in a number of pathologic conditions. We hypothesized that markers of MT, soluble CD14 (sCD14) and lipopolysaccharide (LPS) binding protein (LBP), may be a source of chronic inflammation in older persons and be associated with poorer physical function.
We assessed cross-sectional relationships among two plasma biomarkers of MT (sCD14 and LBP), physical function (hand grip strength, short physical performance battery [SPPB], gait speed, walking distance, and disability questionnaire), and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), TNF-α soluble receptor 1 [TNFsR1]) in 59 older (60–89 years), healthy (no evidence of acute or chronic illness) men and women.
LBP was inversely correlated with SPPB score and grip strength (p = .02 and p < .01, respectively) and positively correlated with CRP (p = 0.04) after adjusting for age, gender, and body mass index. sCD14 correlated with IL-6 (p = .01), TNF-α (p = .05), and TNFsR1 (p < .0001). Furthermore, the correlations between LBP and SPPB and grip strength remained significant after adjusting for each inflammatory biomarker.
In healthy older individuals, LBP, a surrogate marker of MT, is associated with worse physical function and inflammation. Additional study is needed to determine whether MT is a marker for or a cause of inflammation and the associated functional impairments.
PMCID: PMC3636679  PMID: 22960476
Microbial translocation; Inflammation; Physical function; Microbiome
15.  Total and Abdominal Adiposity Are Associated With Inflammation in Older Adults Using a Factor Analysis Approach 
Obesity-related increases in multiple inflammatory markers may contribute to the persistent subclinical inflammation common with advancing age. However, it is unclear if a specific combination of markers reflects the underlying inflammatory state. We used factor analysis to identify inflammatory factor(s) and examine their associations with adiposity in older adults at risk for disability.
Adiponectin, CRP, IL-1ra, IL-1sRII, IL-2sRα, IL-6, IL-6sR, IL-8, IL-15, sTNFRI, sTNFRII, and TNF-α were measured in 179 participants from the Lifestyle Interventions and Independence for Elders Pilot (Mean ± SD age 77 ± 4 years, 76% white, 70% women). Body mass index, waist circumference, and total fat mass were assessed by anthropometry and dual-energy x-ray absorptiometry.
IL-2sRα, sTNFRI, and sTNFRII loaded highest on the first factor (factor 1). CRP, IL-1ra, and IL-6 loaded highest on the second factor (factor 2). Factor 2, but not factor 1, was positively associated with 1-SD increments in waist circumference (β = 0.160 ± 0.057, p = .005), body mass index (β = 0.132 ± 0.053, p = .01), and total fat mass (β = 0.126 ± 0.053, p = .02) after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory medications, comorbidity index, health-related quality of life, and physical function. These associations remained significant after further adjustment for grip strength, but only waist circumference remained associated with inflammation after adjusting for total lean mass. There were no significant interactions between adiposity and muscle mass or strength for either factor.
Greater total and abdominal adiposity are associated with higher levels of an inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide a clinically useful measure of inflammation in this population.
PMCID: PMC3437966  PMID: 22451470
Aging; Adiposity; Inflammation; Muscle impairment; Factor analysis
16.  Exercise Training as a Treatment for Chronic Inflammation in the Elderly 
Persistent, sub-clinical inflammation predisposes to chronic disease, as well as the development of sarcopenia and disability, in frail elderly. Thus, the inflammatory pathway is a potential target for interventions to reduce aging-related disease and disability. This article highlights emerging data suggesting that increasing physical activity could be effective for reducing chronic inflammation in the elderly.
PMCID: PMC2789351  PMID: 19955865
aging; sarcopenia; inflammation; cytokines; physical activity
17.  Acute Impact of Moderate-Intensity and Vigorous-Intensity Exercise Bouts on Daily Physical Activity Energy Expenditure in Postmenopausal Women 
Journal of Obesity  2010;2011:342431.
This study determined whether performing a single moderate- or vigorous-intensity exercise bout impacts daily physical activity energy expenditure (PAEE, by accelerometer). Overweight/obese postmenopausal women underwent a 5-month caloric restriction and moderate- (n = 18) or vigorous-intensity (n = 18) center-based aerobic exercise intervention. During the last month of intervention, in women performing moderate-intensity exercise, PAEE on days with exercise (577.7 ± 219.7 kcal·d−1) was higher (P = .011) than on days without exercise (450.7 ± 140.5 kcal·d−1); however, the difference (127.0 ± 188.1 kcal·d−1) was much lower than the energy expended during exercise. In women performing vigorous-intensity exercise, PAEE on days with exercise (450.6 ± 153.6 kcal·d−1) was lower (P = .047) than on days without exercise (519.2 ± 127.4 kcal·d−1). Thus, women expended more energy on physical activities outside of prescribed exercise on days they did NOT perform center-based exercise, especially if the prescribed exercise was of a higher intensity.
PMCID: PMC2931398  PMID: 20847895
18.  Strength Training for Arthritis Trial (START): design and rationale 
Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression.
This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life.
Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact.
Trial registration, NCT01489462
PMCID: PMC3722013  PMID: 23855596
19.  Exercise Training and Plasma C-reactive Protein and Interleukin-6 in the Elderly 
The purpose of this study was to determine the effects of a long-term exercise intervention on two prominent biomarkers of inflammation (C-reactive protein and interleukin-6) in elderly men and women.
Single-blind, randomized, controlled trial: The Lifestyle Interventions and Independence for Elders trial (LIFE).
The Cooper Institute, Dallas, Texas; Stanford University, Stanford, California; University of Pittsburgh, Pittsburgh, Pennsylvania; and Wake Forest University, Winston-Salem, North Carolina
Elderly (70–89 yrs), non-disabled, community-dwelling men and women at risk for physical disability (n=424).
A 12-month moderate-intensity physical activity (PA) intervention compared to a successful aging (SA) health education intervention.
CRP and IL-6
After adjustment for baseline IL-6, gender, clinic site, diabetes, treatment group, visit, and group by visit interaction, the PA intervention resulted in a lower (P=0.02) IL-6 concentration compared to the SA intervention. The adjusted mean IL-6 at month 12 was 8.5% (0.21 pg/ml) higher in the SA compared to the PA group. There were no significant differences in CRP between the groups at 12 months (P=0.09). Marginally significant interaction effects of the PA intervention by baseline functional status (P=0.051) and IL-6 (above versus below the median; P=0.06) were observed. There was a greater effect of the PA intervention in participants with a lower functional status and those with a higher baseline IL-6.
Increased physical activity results in reduced systemic concentrations of IL-6 in elderly individuals and this benefit is most pronounced in those individuals at the greatest risk for disability and subsequent loss of independence.
PMCID: PMC2683336  PMID: 19016938
exercise training; inflammation; aging; interleukin-6; C-reactive protein
20.  Effects of lifestyle interventions on inflammatory markers in the metabolic syndrome 
Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors which, when present, place individuals at increased risk for cardiovascular morbidity and mortality. In addition to obesity and insulin resistance, inflammation is emerging as a potential etiologic factor of the syndrome. One hypothesis which attempts to unify these factors suggests that obesity contributes to insulin resistance through an increased production of adipose-derived inflammatory cytokines. Currently, lifestyle change is the first line of treatment for MetS and only recently have studies begun to explore the effect of lifestyle interventions in the mediation of inflammation in individuals with MetS.
This review summarizes the strongest evidence (i.e. randomized controlled trial data) for a role of lifestyle interventions (diet and/or exercise) on the improvement of inflammatory biomarkers in people with MetS. Of six studies assessed, lifestyle interventions were consistently successful at improving the inflammatory and metabolic profiles. Interestingly, improvements in the inflammatory profile were found to be largely independent of obesity. Data currently suggest that alterations in dietary composition may be the most effective lifestyle change, although there is a need for more research in this area.
PMCID: PMC3665333  PMID: 21196367
metabolic syndrome; inflammation; exercise; diet; lifestyle intervention
21.  Effects of a 12-Month Physical Activity Intervention on Prevalence of Metabolic Syndrome in Elderly Men and Women 
There is a lack of information on whether exercise training alone can reduce the prevalence of metabolic syndrome (MetS) in elderly men and women.
This study was an ancillary to the Lifestyle Interventions and Independence for Elders Pilot Study, a four-site, single-blind, randomized controlled clinical trial comparing a 12-month physical activity (PA) intervention (N = 180) with a successful aging intervention (N = 181) in elderly (70–89 years) community-dwelling men and women at risk for physical disability. The PA intervention included aerobic, strength, and flexibility exercises, with walking as the primary mode. MetS was defined using the National Cholesterol Education Program criteria.
There was no significant change in body weight or fat mass after either intervention. The trend of MetS prevalence over the intervention period was similar between PA and successful aging groups (p = .77). Overall, the prevalence of MetS decreased significantly from baseline to 6 months (p = .003) but did not change further from 6- to 12-month visits (p = .11). There were no group differences in any individual MetS components (p > .05 for all group by visit interactions). However, in individuals not using medications at any visit to treat MetS components, those in the PA intervention had lower odds of having MetS than those in the successful aging group during follow-up (odds ratio = 0.28, 95% confidence interval = 0.08–0.96).
In this sample, a 12-month PA intervention did not reduce the prevalence of MetS more than a successful aging intervention, perhaps due to the large proportion of individuals taking medications for treating MetS components.
PMCID: PMC3309873  PMID: 22024949
Metabolic syndrome; Elderly; Physical activity
22.  Relation of Pulse Pressure to Long-Distance Gait Speed in Community-Dwelling Older Adults: Findings from the LIFE-P Study 
PLoS ONE  2012;7(11):e49544.
Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.
Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.
Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.
Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.
PMCID: PMC3503986  PMID: 23185357
23.  Does the Amount of Fat Mass Predict Age-Related Loss of Lean Mass, Muscle Strength, and Muscle Quality in Older Adults? 
An excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass and strength with aging. We therefore examined the association of baseline total body fat with changes in leg lean mass, muscle strength, and muscle quality over 7 years of follow-up and whether this link was explained by adipocytokines and insulin resistance.
Data were from 2,307 men and women, aged 70–79 years, participating in the Health, Aging, and Body Composition study. Total fat mass was acquired from dual energy X-ray absorptiometry. Leg lean mass was assessed by dual energy X-ray absorptiometry in Years 1, 2, 3, 4, 5, 6, and 8. Knee extension strength was measured by isokinetic dynamometer in Years 1, 2, 4, 6, and 8. Muscle quality was calculated as muscle strength divided by leg lean mass.
Every SD greater fat mass was related to 1.3 kg more leg lean mass at baseline in men and 1.5 kg in women (p < .01). Greater fat mass was also associated with a greater decline in leg lean mass in both men and women (0.02 kg/year, p < .01), which was not explained by higher levels of adipocytokines and insulin resistance. Larger fat mass was related to significantly greater muscle strength but significantly lower muscle quality at baseline (p < .01). No significant differences in decline of muscle strength and quality were found.
High fatness was associated with lower muscle quality, and it predicts accelerated loss of lean mass. Prevention of greater fatness in old age may decrease the loss of lean mass and maintain muscle quality and thereby reducing disability and mobility impairments.
PMCID: PMC3184893  PMID: 21572082
Adipose tissue; Muscle mass; Muscle strength; Obesity; Aging
24.  Change in 25-Hydroxyvitamin D and Physical Performance in Older Adults 
Vitamin D deficiency is common among older adults and is associated with poor physical performance; however, studies examining longitudinal changes in 25-hydroxyvitamin D (25[OH]D) and physical performance are lacking. We examined the association between 25(OH)D and physical performance over 12 months in older adults participating in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), a multicenter physical activity intervention trial.
Plasma 25(OH)D and physical performance, assessed by the short physical performance battery (SPPB) and 400-m walk test, were measured at baseline, 6-month, and 12-month follow-up in community-dwelling adults aged 70–89 years at risk for disability (n = 368). Mixed models were used to examine the association between 25(OH)D and physical performance adjusting for demographics, intervention group, season, body mass index, and physical activity.
One half of the participants were vitamin D deficient (25[OH]D < 20 ng/mL) at baseline. In cross-sectional analyses, vitamin D deficiency was associated with lower SPPB scores and slower 400-m walk speeds (mean difference [SE]: 0.35 [0.16], p = .03 and 0.04 [0.02] m/s, p = .01, respectively). Although baseline 25(OH)D status was not significantly associated with change in physical performance over 12 months, individuals who were vitamin D deficient at baseline but no longer deficient at follow-up had significant improvements in SPPB scores (mean difference [SE]: 0.55 [0.22], p = .01) compared with those whose 25(OH)D status remained the same.
Increases in 25(OH)D to greater than or equal to 20 ng/mL were associated with clinically significant improvements in physical performance among older adults.
PMCID: PMC3055282  PMID: 21325343
Vitamin D; Physical performance; Aging
25.  The Effect of Pioglitazone and Resistance Training on Body Composition in Older Men and Women Undergoing Hypocaloric Weight Loss 
Obesity (Silver Spring, Md.)  2011;19(8):1636-1646.
Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m2) and women (n = 40, BMI = 33.3 ± 4.9 kg/m2) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (−1,160 vs. −647 cm3, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (−104 vs. −298 cm3, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: −43 vs. −88 cm3, P = 0.005; women: −34 vs. −59 cm3, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
PMCID: PMC3091968  PMID: 21233810

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