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1.  Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial 
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.
doi:10.2147/CIA.S17001
PMCID: PMC3131984  PMID: 21753869
obesity; weight loss; physical function; oxidative stress; inflammation; walking speed
2.  Influence of diet, exercise and serum vitamin D on sarcopenia in post-menopausal women 
Purpose
To investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on lean mass and the measurements defining sarcopenia in postmenopausal women, and to examine the potential moderating effect of serum 25-hydroxyvitamin D (25(OH)D) and age.
Methods
439 overweight and obese postmenopausal women were randomized to: diet modification (N=118); exercise (N=117), diet+exercise (N=117), or control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. Total and appendicular lean mass were quantified by dual Xray absorptiometry (DXA) at baseline and 12 months. A skeletal muscle index (SMI=appendicular lean mass (kg)/m2) and the prevalence of sarcopenia (SMI<5.67 kg/m2) were calculated. Serum 25(OH)D was assayed using a competitive chemiluminescent immunoassay.
Results
Dietary weight loss resulted in a significant decrease in lean mass, and a borderline significant decrease in appendicular lean mass and SMI compared to controls. In contrast, aerobic exercise significantly preserved appendicular lean mass and SMI. Diet + exercise attenuated the loss of appendicular lean mass and SMI compared to diet alone, and did not result in significant loss of total- or appendicular lean mass compared to controls. Neither serum 25(OH)D nor age were significant moderators of the intervention effects.
Conclusions
Aerobic exercise added to dietary weight loss can attenuate the loss of appendicular lean mass during weight loss, and may be effective for the prevention and treatment of sarcopenia among overweight and obese postmenopausal women.
doi:10.1249/MSS.0b013e31827aa3fa
PMCID: PMC3594522  PMID: 23190588
caloric restriction; weight loss; 25-hydroxyvitamin D; ageing
3.  Optimal management of sarcopenia 
Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function which occurs as a consequence of aging. With a growing older population, there has been great interest in developing approaches to counteract the effects of sarcopenia, and thereby reduce the age-related decline and disability. This paper reviews (1) the mechanisms of sarcopenia, (2) the diagnosis of sarcopenia, and (3) the potential interventions for sarcopenia. Multiple factors appear to be involved in the development of sarcopenia including the loss of muscle mass and muscle fibers, increased inflammation, altered hormonal levels, poor nutritional status, and altered renin–angiotensin system. The lack of diagnostic criteria to identify patients with sarcopenia hinders potential management options. To date, pharmacological interventions have shown limited efficacy in counteracting the effects of sarcopenia. Recent evidence has shown benefits with angiotensin-converting enzyme inhibitors; however, further randomized controlled trials are required. Resistance training remains the most effective intervention for sarcopenia; however, older people maybe unable or unwilling to embark on strenuous exercise training programs.
PMCID: PMC2938029  PMID: 20852669
aged; muscle function; sarcopenia
4.  Land-based versus aquatic resistance therapeutic exercises for older women with sarcopenic obesity: study protocol for a randomised controlled trial 
Trials  2013;14:296.
Background
Sarcopenic obesity is a health condition that combines excess adipose tissue and loss of muscle mass and strength. Sarcopenic obesity predisposes to more functional disabilities than obesity or sarcopenia alone. Progressive resistance exercises are recommended for older people as a potential treatment for sarcopenia and also for obesity. However, there is a lack of evidence indicating which programmes are best applied to older people, and no studies have investigated their effects on sarcopenic obese people. The aims of this protocol study are to investigate and compare the efficacy of land-based and aquatic resistance exercise programmes on improving muscle performance, functional capacity and quality of life of older women with sarcopenic obesity.
Methods/Design
This is a protocol study for a parallel randomised controlled clinical trial. Eligible participants are older women (≥65 years) with a body mass index ≥30 kg/m 2 and hand grip strength ≤21 kg force. A total sample of 36 participants will be randomly allocated to one of the intervention groups in blocks of three: land-based, aquatic or control. Each intervention group will undergo 2-week sessions of a 10-week therapeutic exercise programme for strength, power and endurance training of the lower-limb muscles. Participants in the control group will not participate in any strengthening activity for lower limbs and will receive telephone calls once a week. Baseline and final evaluation of outcomes will encompass muscle performance of the lower limbs assessed by an isokinetic dynamometer; functional tests of usual walking speed, maximal walking speed (shuttle walking test), stair speed and the Short Physical Performance Battery; and health-related quality of life (Medical Outcomes Study Short Form Questionnaire – SF-36). Data collectors will be blinded to randomisation and will not be in touch with participants during the interventions.
Discussion
This study is the first randomised controlled trial designed to evaluate resistance exercises in older patients with sarcopenic obesity. If our hypothesis proves correct, both intervention programmes will be effective, with the land-based exercises conferring better results in muscle performance.
Trial registration
Registro Brasileiro de Ensaios Clínicos: RBR-9p5q67
doi:10.1186/1745-6215-14-296
PMCID: PMC3848713  PMID: 24041219
Older people; Women; Sarcopenic obesity; Resistance exercises
5.  One size may not fit all: anti-aging therapies and sarcopenia 
Aging (Albany NY)  2011;3(12):1142-1153.
Sarcopenia refers to age-related loss of muscle mass and function. Several age-related changes occur in skeletal muscle including a decrease in myofiber size and number and a diminished ability of satellite cells to activate and proliferate upon injury leading to impaired muscle remodeling. Although the molecular mechanisms underlying sarcopenia are unknown, it is tempting to hypothesize that interplay between biological and environmental factors cooperate in a positive feedback cycle contributing to the progression of sarcopenia. Indeed many essential biological mechanisms such as apoptosis and autophagy and critical signaling pathways involved in skeletal muscle homeostasis are altered during aging and have been linked to loss of muscle mass. Moreover, the environmental effects of the sedentary lifestyle of older people further promote and contribute the loss of muscle mass. There are currently no widely accepted therapeutic strategies to halt or reverse the progression of sarcopenia. Caloric restriction has been shown to be beneficial as a sarcopenia and aging antagonist. Such results have made the search for caloric restriction mimetics (CRM) a priority. However given the mechanisms of action, some of the currently investigated CRMs may not combat sarcopenia. Thus, sarcopenia may represent a unique phenotypic feature of aging that requires specific and individually tailored therapeutic strategies.
PMCID: PMC3273894  PMID: 22184279
sarcopenia; therapy; caloric restriction; caloric restriction mimetics; anti-aging; skeletal muscle
6.  Dietary Weight-Loss and Exercise Effects on Insulin Resistance in Postmenopausal Women 
Background
Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight-loss and exercise on insulin sensitivity and restoration of normal fasting glucose in mid-aged and older women.
Design
Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010.
Setting/participants
439 inactive, overweight/obese postmenopausal women. Interventions: Women were assigned to: dietary weight loss (n=118), exercise (n=117), exercise+diet (n=117), or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity.
Main outcome measures
12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR).
Results
A significant improvement in HOMA-IR was detected in the diet (−24%, p<0.001) and exercise+ diet (−26%, p<0.001) groups, but not in the exercise (−9%, p=0.22) group compared to controls (−2%); these effects were similar in middle-aged (50–60 years) and older women (aged 60–75 years). Among those with impaired fasting glucose (5.6–6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were: 2.5 (0.8, 8.4), 2.76 (0.8, 10.0), and 3.1 (1.0, 9.9) in the diet, exercise+diet, and exercise group, respectively, compared to controls.
Conclusions
Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women.
doi:10.1016/j.amepre.2011.06.042
PMCID: PMC3185302  PMID: 21961463
7.  Resistance Exercise Reverses Aging in Human Skeletal Muscle 
PLoS ONE  2007;2(5):e465.
Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training.
doi:10.1371/journal.pone.0000465
PMCID: PMC1866181  PMID: 17520024
8.  The Effect of Physiological Stimuli on Sarcopenia; Impact of Notch and Wnt Signaling on Impaired Aged Skeletal Muscle Repair 
The age-related loss of skeletal muscle mass and function that is associated with sarcopenia can result in ultimate consequences such as decreased quality of life. The causes of sarcopenia are multifactorial and include environmental and biological factors. The purpose of this review is to synthesize what the literature reveals in regards to the cellular regulation of sarcopenia, including impaired muscle regenerative capacity in the aged, and to discuss if physiological stimuli have the potential to slow the loss of myogenic potential that is associated with sarcopenia. In addition, this review article will discuss the effect of aging on Notch and Wnt signaling, and whether physiological stimuli have the ability to restore Notch and Wnt signaling resulting in rejuvenated aged muscle repair. The intention of this summary is to bring awareness to the benefits of consistent physiological stimulus (exercise) to combating sarcopenia as well as proclaiming the usefulness of contraction-induced injury models to studying the effects of local and systemic influences on aged myogenic capability.
doi:10.7150/ijbs.4262
PMCID: PMC3371570  PMID: 22701343
sarcopenia; physiological stimuli
9.  Role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in denervation-induced atrophy in aged muscle: facts and hypotheses 
Aging-related loss of muscle mass, a biological process named sarcopenia, contributes to mobility impairment, falls, and physical frailty, resulting in an impaired quality of life in older people. In view of the aging of our society, understanding the underlying mechanisms of sarcopenia is a major health-care imperative. Evidence obtained from human and rodent studies demonstrates that skeletal muscle denervation/reinnervation cycles occur with aging, and that progressive failure of myofiber reinnervation is a major cause of the accelerating phase of sarcopenia in advanced age. However, the mechanisms responsible for the loss of myofiber innervation with aging remain unknown. The two major strategies that counteract sarcopenia, that is, caloric restriction and endurance training, are well known to protect neuromuscular junction (NMJ) integrity, albeit through undefined mechanisms. Interestingly, both of these interventions better preserve PGC-1α expression with aging, a transcriptional coactivator which has recently been shown to regulate key proteins involved in maintaining NMJ integrity. We therefore propose that the aging-related decline in PGC-1α may be a central mechanism promoting instability of the NMJ and consequently, aging-related alterations of myofiber innervation in sarcopenia. Similarly, the promotion of PGC-1α expression by both caloric restriction and exercise training may be fundamental to their protective benefits for aging muscle by better preserving NMJ integrity.
doi:10.1186/2046-2395-2-13
PMCID: PMC3922934  PMID: 24472348
Skeletal muscle; Aging; Sarcopenia; PGC-1α; Denervation; Reinnervation
10.  The Influence of Energetic Factors on Biomarkers of Postmenopausal Breast Cancer Risk 
Strong and consistent evidence exists that physical activity reduces breast cancer risk by 10-25 %, and several proposed biologic mechanisms have now been investigated in randomized, controlled, exercise intervention trials. Leading hypothesized mechanisms relating to postmenopausal breast cancer include adiposity, endogenous sex hormones, insulin resistance, and chronic low-grade inflammation. In addition, other pathways are emerging as potentially important, including those involving oxidative stress and telomere length, global DNA hypomethylation, immune function, and vitamin D exposure. Recent exercise trials in overweight/obese postmenopausal women implicate weight loss as a mechanism whereby exercise induces favorable changes in circulating estradiol levels and other biomarkers as well. Still it is plausible that some exercise-induced biomarker changes do not require loss of body fat, whereas others depend on abdominal fat loss. We highlight the latest findings from randomized, controlled trials of healthy postmenopausal women, relating exercise to proposed biomarkers for postmenopausal breast cancer risk.
doi:10.1007/s13668-013-0069-8
PMCID: PMC3921460  PMID: 24563822
Breast cancer; Postmenopausal women; Randomized trials; Physical activity; Exercise; Weight loss; Adiposity; Biomarkers; Sex hormones; Estrogen; Biomechanisms
11.  Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial 
Background
Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL.
Methods
This study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL.
Results
Twelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness.
Conclusions
A combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.
doi:10.1186/1479-5868-8-118
PMCID: PMC3215656  PMID: 22026966
health-related quality of life; exercise; dietary weight loss; postmenopausal women
12.  Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy 
Biological chemistry  2013;394(3):393-414.
Muscle loss during aging and disuse is a highly prevalent and disabling condition, but knowledge about cellular pathways mediating muscle atrophy is still limited. Given the postmitotic nature of skeletal myocytes, the maintenance of cellular homeostasis relies on the efficiency of cellular quality control mechanisms. In this scenario, alterations in mitochondrial function are considered a major factor underlying sarcopenia and muscle atrophy. Damaged mitochondria are not only less bioenergetically efficient, but also generate increased amounts of reactive oxygen species, interfere with cellular quality control mechanisms, and display a greater propensity to trigger apoptosis. Thus, mitochondria stand at the crossroad of signaling pathways that regulate skeletal myocyte function and viability. Studies on these pathways have sometimes provided unexpected and counterintuitive results, which suggests that they are organized into a complex, heterarchical network that is currently insufficiently understood. Untangling the complexity of such a network will likely provide clinicians with novel and highly effective therapeutics to counter the muscle loss associated with aging and disuse. In this review, we summarize the current knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of targeting specific processes to treat these conditions.
doi:10.1515/hsz-2012-0247
PMCID: PMC3976204  PMID: 23154422
apoptosis; autophagy; fission; fusion; mitophagy; oxidative stress
13.  Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese post-menopausal women 
Obesity (Silver Spring, Md.)  2011;20(8):1628-1638.
Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet towards whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45 min aerobic exercise 5 d/wk. Participants were predominantly non-Hispanic Whites (85%) with a mean age of 58.0±5.0 years, a mean BMI of 30.9±4.0 kg/m2 and an average of 47.8±4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants’ intervention assignment. 399 women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was −8.5% for the D group (P<0.0001 vs. C), −2.4% for the E group (P=0.03 vs. C), and −10.8% for the D+E group (P<0.0001 vs. C), while the C group experienced a non-significant −0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.
doi:10.1038/oby.2011.76
PMCID: PMC3406229  PMID: 21494229
Body weight; body composition; weight-reducing diet; exercise intervention; women
14.  Sarcopenic Obesity and Endocrinal Adaptation with Age 
In normal aging, changes in the body composition occur that result in a shift toward decreased muscle mass and increased fat mass. The loss of muscle mass that occurs with aging is termed sarcopenia and is an important cause of frailty, disability, and loss of independence in older adults. Age-related changes in the body composition as well as the increased prevalence of obesity determine a combination of excess weight and reduced muscle mass or strength, recently defined as sarcopenic obesity. Weight gain increases total/abdominal fat, which, in turn, elicits inflammation and fatty infiltration in muscle. Sarcopenic obesity appears to be linked with the upregulation of TNF-α, interleukin (IL)-6, leptin, and myostatin and the downregulation of adiponectin and IL-15. Multiple combined exercise and mild caloric restriction markedly attenuate the symptoms of sarcopenic obesity. Intriguingly, the inhibition of myostatin induced by gene manipulation or neutralizing antibody ameliorates sarcopenic obesity via increased skeletal muscle mass and improved glucose homeostasis. In this review, we describe the possible influence of endocrinal changes with age on sarcopenic obesity.
doi:10.1155/2013/204164
PMCID: PMC3639625  PMID: 23690769
15.  Novel Intriguing Strategies Attenuating to Sarcopenia 
Journal of Aging Research  2012;2012:251217.
Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA) or ursolic acid, etc.) for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant.
doi:10.1155/2012/251217
PMCID: PMC3303581  PMID: 22500226
16.  A Behavioral Weight-Loss Intervention in Persons with Serious Mental Illness 
The New England journal of medicine  2013;368(17):1594-1602.
BACKGROUND
Overweight and obesity are epidemic among persons with serious mental illness, yet weight-loss trials systematically exclude this vulnerable population. Lifestyle interventions require adaptation in this group because psychiatric symptoms and cognitive impairment are highly prevalent. Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness.
METHODS
We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and randomly assigned them to an intervention or a control group. Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions. Weight change was assessed at 6, 12, and 18 months.
RESULTS
Of 291 participants who underwent randomization, 58.1% had schizophrenia or a schizoaffective disorder, 22.0% had bipolar disorder, and 12.0% had major depression. At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.3, and the mean weight was 102.7 kg (225.9 lb). Data on weight at 18 months were obtained from 279 participants. Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit. At 18 months, the mean between-group difference in weight (change in intervention group minus change in control group) was −3.2 kg (−7.0 lb, P = 0.002); 37.8% of the participants in the intervention group lost 5% or more of their initial weight, as compared with 22.7% of those in the control group (P = 0.009). There were no significant between-group differences in adverse events.
CONCLUSIONS
A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness. Given the epidemic of obesity and weight-related disease among persons with serious mental illness, our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population.
doi:10.1056/NEJMoa1214530
PMCID: PMC3743095  PMID: 23517118
17.  Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults 
PLoS ONE  2010;5(5):e10778.
The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; ♀  =  ♂). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.
doi:10.1371/journal.pone.0010778
PMCID: PMC2875392  PMID: 20520725
18.  Changes in Weight, Waist Circumference and Compensatory Responses with Different Doses of Exercise among Sedentary, Overweight Postmenopausal Women 
PLoS ONE  2009;4(2):e4515.
Background
It has been suggested that exercise training results in compensatory mechanisms that attenuate weight loss. However, this has only been examined with large doses of exercise. The goal of this analysis was to examine actual weight loss compared to predicted weight loss (compensation) across different doses of exercise in a controlled trial of sedentary, overweight or obese postmenopausal women (n = 411).
Methodology/Principal Findings
Participants were randomized to a non-exercise control (n = 94) or 1 of 3 exercise groups; exercise energy expenditure of 4 (n = 139), 8 (n = 85), or 12 (n = 93) kcal/kg/week (KKW). Training intensity was set at the heart rate associated with 50% of each woman's peak VO2 and the intervention period was 6 months. All exercise was supervised. The main outcomes were actual weight loss, predicted weight loss (exercise energy expenditure/ 7700 kcal per kg), compensation (actual minus predicted weight loss) and waist circumference. The study sample had a mean (SD) age 57.2 (6.3) years, BMI of 31.7 (3.8) kg/m2, and was 63.5% Caucasian. The adherence to the intervention was >99% in all exercise groups. The mean (95% CI) weight loss in the 4, 8 and 12 KKW groups was −1.4 (−2.0, −0.8), −2.1 (−2.9, −1.4) and −1.5 (−2.2, −0.8) kg, respectively. In the 4 and 8 KKW groups the actual weight loss closely matched the predicted weight loss of −1.0 and −2.0 kg, respectively, resulting in no significant compensation. In the 12 KKW group the actual weight loss was less than the predicted weight loss (−2.7 kg) resulting in 1.2 (0.5, 1.9) kg of compensation (P<0.05 compared to 4 and 8 KKW groups). All exercise groups had a significant reduction in waist circumference which was independent of changes in weight.
Conclusion
In this study of previously sedentary, overweight or obese, postmenopausal women we observed no difference in the actual and predicted weight loss with 4 and 8 KKW of exercise (72 and 136 minutes respectively), while the 12 KKW (194 minutes) produced only about half of the predicted weight loss. However, all exercise groups had a significant reduction in waist circumference which was independent of changes in weight.
Trial Registration
ClinicalTrials.gov NCT 00011193
doi:10.1371/journal.pone.0004515
PMCID: PMC2639700  PMID: 19223984
19.  Effectiveness of exercise and protein supplementation intervention on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia 
Sarcopenia, characterized as muscle loss that occurs with aging, is a major health problem in an aging population, due to its implications on mobility, quality of life, and fall risk. Protein supplementation could improve the physical fitness by increasing protein anabolism, and exercise has a documented evidence of positive effect on functional status among the elderly. However, the combined effect of both protein supplementation and exercise has not been investigated among sarcopenic elderly in the Asian population. Thus, this study aimed to determine the effectiveness of exercise intervention and protein supplementation either alone or in combination for 12 weeks, on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia. Sixty five sarcopenic elderly Malays aged 60–74 years were assigned to the control group, exercise group (ExG), protein supplementation group (PrG), or the combination of exercise and protein supplementation group. A significant interaction effect between body weight and body mass index (BMI) was observed, with the PrG (−2.1% body weight, −1.8% BMI) showing the highest reductions. Further, there was a decrease in % body fat (−4.5%) and an increase in fat-free mass (kg) (+5.7%) in the ExG after 12 weeks (P < 0.05). The highest increments in lower and upper body strength were observed in the PrG (73.2%) and ExG (47.6%), respectively. In addition, the ExG showed a reduction in superoxide dismutase (SOD) levels, and both interventions did not alter either lipid or protein oxidation. In conclusion, the exercise program was found to improve muscle strength and body composition, while protein supplementation reduced body weight and increased upper body strength, among sarcopenic elderly in Malaysia.
doi:10.2147/CIA.S46826
PMCID: PMC3797615  PMID: 24143082
protein supplement; aging population; sarcopenic elderly; Malaysia; Asian
20.  Web-based interventions for weight loss and weight maintenance among rural midlife and older women: protocol for a randomized controlled trial 
BMC Public Health  2011;11:521.
Background
Weight loss is challenging and maintenance of weight loss is problematic among midlife and older rural women. Finding effective interventions using innovative delivery methods that can reach underserved and vulnerable populations of overweight and obese rural women is a public health challenge.
Methods/Design
This Women Weigh-In for Wellness (The WWW study) randomized-controlled trial is designed to compare the effectiveness of theory-based behavior-change interventions using (1) website only, (2) website with peer-led support, or (3) website with professional email-counseling to facilitate initial weight loss (baseline to 6 months), guided continuing weight loss and maintenance (7-18 months) and self-directed weight maintenance (19-30 months) among rural women ages 45-69 with a BMI of 28-45. Recruitment efforts using local media will target 306 rural women who live within driving distance of a community college site where assessments will be conducted at baseline, 3, 6, 12, 18, 24 and 30 months by research nurses blinded to group assignments. Primary outcomes include changes in body weight, % weight loss, and eating and activity behavioral and biomarkers from baseline to each subsequent assessment. Secondary outcomes will be percentage of women achieving at least 5% and 10% weight loss without regain from baseline to 6, 18, and 30 months and achieving healthy eating and activity targets. Data analysis will use generalized estimating equations to analyze average change across groups and group differences in proportion of participants achieving target weight loss levels.
Discussion
The Women Weigh-In for Wellness study compares innovative web-based alternatives for providing lifestyle behavior-change interventions for promoting weight loss and weight maintenance among rural women. If effective, such interventions would offer potential for reducing overweight and obesity among a vulnerable, hard-to-reach, population of rural women.
Trial Registration
ClinicalTrials.gov: NCT01307644
doi:10.1186/1471-2458-11-521
PMCID: PMC3152906  PMID: 21718512
21.  Addition of Aerobic Exercise to a Weight Loss Program Increases BMD, with an Associated Reduction in Inflammation in Overweight Postmenopausal Women 
Calcified tissue international  2009;84(4):257-265.
Increased inflammation and weight loss are associated with a reduction in bone mineral density (BMD). Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines. We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers, thus mediating changes in BMD. This was a nonrandomized controlled trial. Eighty-six overweight and obese postmenopausal women (50–70 years of age; BMI, 25–40 kg/m2) participated in a weight loss (WL; n = 40) or weight loss plus walking (WL + AEX; n = 46) program. Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry, interleukin-6, tumor necrosis factor-α, soluble receptors of IL-6, and TNF-α (sTNFR1 and sTNFR2; receptors in a subset of the population), VO2 max, fat mass, and lean mass. Weight decreased in the WL (p < 0.001) and WL + AEX (p < 0.001) groups. VO2 max increased (p < 0.001) after WL + AEX. There was a 2% increase in femoral neck BMD in the WL + AEX group (p = 0.001), which was significantly different from the WL group. The change in sTNFR1 was significantly associated with the change in femoral neck BMD (p < 0.05). The change in VO2 max was an independent predictor of the change in femoral neck BMD. Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women.
doi:10.1007/s00223-009-9232-z
PMCID: PMC2926800  PMID: 19280097
Aging; Cytokines; Inflammation; Exercise; Weight loss
22.  Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip BMD induced by weight loss despite decline in bone-active hormones* 
Weight-loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight-loss therapy should include an intervention to minimize bone loss such as exercise training (ET). The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 yrs) obese (BMI ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group P<.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group P<.001) Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%) while they decreased in the exercise group (−13% and −15%) (between-group P<.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (P=.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%) and diet-exercise (−38% and −13%) groups, not in the exercise and control groups (between-group P=.001). Multivariate analyses revealed that changes in lean body mass (β=.33), serum osteocalcin (β= −.24), and 1-RM strength (β=.23) were independent predictors of changes in hip BMD (all P<.05). In conclusion, the addition of ET to weight-loss therapy among obese older adults prevents weight-loss-induced increase in bone turnover and attenuates weight-loss-induced reduction in hip BMD despite weight-loss-induced decrease in bone-active hormones.
doi:10.1002/jbmr.475
PMCID: PMC3206995  PMID: 21786319
23.  WEIGHT LOSS: A NOVEL AND EFFECTIVE TREATMENT FOR URINARY INCONTINENCE 
The Journal of urology  2005;174(1):190-195.
Purpose
We evaluated the effect of weight loss on urinary incontinence (UI) in overweight and obese women.
Materials and Methods
A randomized, controlled clinical trial was conducted among overweight and obese women experiencing at least 4 UI episodes per week. Women were randomly assigned to a 3-month liquid diet weight reduction program (24 in the immediate intervention group) or a wait-list delayed intervention group (24 in the wait-list control group). Participants in the wait-list control group began the weight reduction program in month 3 of the study. All women were followed for 6 months after completing the weight reduction program. Wilcoxon tests were used to compare intergroup differences in change in weekly UI episodes and quality of life scores.
Results
A total of 48 women were randomized and 40 were assessed 3 months after randomization. Median (with 25% to 75% interquartile range [IQR]) baseline age was 52 years (IQR 47 to 59), weight was 97 kg (IQR 87 to 106) and UI episodes were 21 weekly (IQR 11 to 33). Women in the immediate intervention group had a 16 kg (IQR 9 to 20) weight reduction compared with 0 kg (IQR −2 to 2) in the wait-list control group (p <0.0001). The immediate intervention group experienced a 60% reduction (IQR 30% to 89%) in weekly UI episodes compared with 15% (IQR −9% to 25%) in the wait-list control group (p <0.0005) and had greater improvement in quality of life scores. Stress (p =0.003) and urge (p =0.03) incontinent episodes decreased in the immediate intervention vs wait-list control group. Following the weight reduction program the wait-list control group experienced a similar median reduction in weekly UI episodes (71%). Among all 40 women mean weekly UI episodes decreased 54% (95% CI 40% to 69%) after weight reduction and the improvement was maintained for 6 months.
Conclusions
Weight reduction is an effective treatment for overweight and obese women with UI. Weight loss of 5% to 10% has an efficacy similar to that of other nonsurgical treatments and should be considered a first line therapy for incontinence.
doi:10.1097/01.ju.0000162056.30326.83
PMCID: PMC1557356  PMID: 15947625
urinary incontinence; obesity; diet therapy; weight loss; female
24.  The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale 
Background
Obesity is the most modifiable risk factor, and dietary induced weight loss potentially the best nonpharmacologic intervention to prevent or to slow osteoarthritis (OA) disease progression. We are currently conducting a study to test the hypothesis that intensive weight loss will reduce inflammation and joint loads sufficiently to alter disease progression, either with or without exercise. This article describes the intervention, the empirical evidence to support it, and test-retest reliability data.
Methods/Design
This is a prospective, single-blind, randomized controlled trial. The study population consists of 450 overweight and obese (BMI = 27–40.5 kg/m2) older (age ≥ 55 yrs) adults with tibiofemoral osteoarthritis. Participants are randomized to one of three 18-month interventions: intensive dietary restriction-plus-exercise; exercise-only; or intensive dietary restriction-only. The primary aims are to compare the effects of these interventions on inflammatory biomarkers and knee joint loads. Secondary aims will examine the effects of these interventions on function, pain, and mobility; the dose response to weight loss on disease progression; if inflammatory biomarkers and knee joint loads are mediators of the interventions; and the association between quadriceps strength and disease progression.
Results
Test-retest reliability results indicated that the ICCs for knee joint load variables were excellent, ranging from 0.86 – 0.98. Knee flexion/extension moments were most affected by BMI, with lower reliability with the highest tertile of BMI. The reliability of the semi-quantitative scoring of the knee joint using MRI exceeded previously reported results, ranging from a low of 0.66 for synovitis to a high of 0.99 for bone marrow lesion size.
Discussion
The IDEA trial has the potential to enhance our understanding of the OA disease process, refine weight loss and exercise recommendations in this prevalent disease, and reduce the burden of disability.
Trial Registration
NCT00381290
doi:10.1186/1471-2474-10-93
PMCID: PMC2729726  PMID: 19638215
25.  Anorexia of Aging: A Modifiable Risk Factor for Frailty 
Nutrients  2013;5(10):4126-4133.
Anorexia of aging, defined as a loss of appetite and/or reduced food intake, affects a significant number of elderly people and is far more prevalent among frail individuals. Anorexia recognizes a multifactorial origin characterized by various combinations of medical, environmental and social factors. Given the interconnection between weight loss, sarcopenia and frailty, anorexia is a powerful, independent predictor of poor quality of life, morbidity and mortality in older persons. One of the most important goals in the management of older, frail people is to optimize their nutritional status. To achieve this objective it is important to identify subjects at risk of anorexia and to provide multi-stimulus interventions that ensure an adequate amount of food to limit and/or reverse weight loss and functional decline. Here, we provide a brief overview on the relevance of anorexia in the context of sarcopenia and frailty. Major pathways supposedly involved in the pathogenesis of anorexia are also illustrated. Finally, the importance of treating anorexia to achieve health benefits in frail elders is highlighted.
doi:10.3390/nu5104126
PMCID: PMC3820063  PMID: 24128975
elderly; sarcopenia; ghrelin; malnutrition; weight loss; disability; energy metabolism

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