Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis

It remains unclear as to what extent resistance training (RT) can attenuate muscle loss during caloric restriction (CR) interventions in humans. The objective here is to address if RT could attenuate muscle loss induced by CR in obese elderly individuals, through summarized effects of previous studies. Databases MEDLINE, Embase and Web of Science were used to perform a systematic search between July and August 2017. Were included in the review randomized clinical trials (RCT) comparing the effects of CR with (CRRT) or without RT on lean body mass (LBM), fat body mass (FBM), and total body mass (BM), measured by dual-energy X-ray absorptiometry, on obese elderly individuals. The six RCTs included in the review applied RT three times per week, for 12 to 24 weeks, and most CR interventions followed diets of 55% carbohydrate, 15% protein, and 30% fat. RT reduced 93.5% of CR-induced LBM loss (0.819 kg [0.364 to 1.273]), with similar reduction in FBM and BM, compared with CR. Furthermore, to address muscle quality, the change in strength/LBM ratio tended to be different (p = 0.07) following CRRT (20.9 ± 23.1%) and CR interventions (−7.5 ± 9.9%). Our conclusion is that CRRT is able to prevent almost 100% of CR-induced muscle loss, while resulting in FBM and BM reductions that do not significantly differ from CR.

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title: Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.
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title: Weight loss larger than 10% is needed for general improvement of levels of circulating adiponectin and markers of inflammation in obese subjects: a 3-year weight loss study.
abstract: To investigate the effects of: I) short- (8 weeks), II) long-term (3 years) weight loss, and III) the degree of weight loss on circulating levels of adiponectin, high sensitive-C reactive protein (hs-CRP), and fibrinogen in obese subjects. Moreover, to evaluate the effect of the lipase inhibitor, orlistat, on these parameters.



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title: A systematic review of the separate and combined effects of energy restriction and exercise on fat-free mass in middle-aged and older adults: implications for sarcopenic obesity.
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title: Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia.
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title: Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis.
abstract: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training. However, there is much discrepancy in the literature regarding the proposed benefits of protein supplementation during prolonged resistance-type exercise training in younger and older populations.



The objective of the study was to define the efficacy of protein supplementation to augment the adaptive response of the skeletal muscle to prolonged resistance-type exercise training in younger and older populations.



A systematic review of interventional evidence was performed through the use of a random-effects meta-analysis model. Data from the outcome variables fat-free mass (FFM), fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition maximum (1-RM) leg press strength were collected from randomized controlled trials (RCTs) investigating the effect of dietary protein supplementation during prolonged (>6 wk) resistance-type exercise training.



Data were included from 22 RCTs that included 680 subjects. Protein supplementation showed a positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91 kg; P < 0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg; 95% CI: 6.4, 20.7 kg; P < 0.005) compared with a placebo after prolonged resistance-type exercise training in younger and older subjects.



Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects.

title: Protein Supplementation Does Not Significantly Augment the Effects of Resistance Exercise Training in Older Adults: A Systematic Review
abstract: Physical activity and nutritional supplementation interventions may be used to ameliorate age-related loss of skeletal muscle mass and function. Previous reviews have demonstrated the beneficial effects of resistance exercise training (RET) combined with protein or essential amino acids (EAA) in younger populations. Whether or not older adults also benefit is unclear. The aim of this review was to determine whether regular dietary supplementation with protein/EAA during a RET regimen augments the effects of RET on skeletal muscle in older adults.  A literature search was conducted in August 2015 using MEDLINE, EMBASE, SPORTDiscus, and CINAHL Plus to identify all controlled trials using a RET regimen with and without protein/EAA supplementation. Outcome variables included muscle strength, muscle size, functional ability, and body composition.  Fifteen studies fulfilled the eligibility criteria, including 917 participants with a mean age of 77.4 years. Studies involving both healthy participants and those described as frail or sarcopenic were included. Overall, results indicated that protein supplementation did not significantly augment the effects of RET on any of the specified outcomes. Exceptions included some measures of muscle strength (3 studies) and body composition (2 studies). Meta-analyses were conducted but were limited because of methodologic differences between studies, and results were inconclusive.  Systematic review and meta-analysis of controlled trials reveal that protein/EAA supplementation does not significantly augment the effects of progressive RET in older adults.

title: Effects of resistance training with and without caloric restriction on physical function and mobility in overweight and obese older adults: a randomized controlled trial.
abstract: Resistance training (RT) improves muscle strength and overall physical function in older adults. RT may be particularly important in the obese elderly who have compromised muscle function. Whether caloric restriction (CR) acts synergistically with RT to enhance function is unknown.



As the primary goal of the Improving Muscle for Functional Independence Trial (I'M FIT), we determined the effects of adding CR for weight loss on muscle and physical function responses to RT in older overweight and obese adults.



I'M FIT was a 5-mo trial in 126 older (65-79 y) overweight and obese men and women who were randomly assigned to a progressive, 3-d/wk, moderate-intensity RT intervention with a weight-loss intervention (RT+CR) or without a weight-loss intervention (RT). The primary outcome was maximal knee extensor strength; secondary outcomes were muscle power and quality, overall physical function, and total body and thigh compositions.



Body mass decreased in the RT+CR group but not in the RT group. Fat mass, percentage of fat, and all thigh fat volumes decreased in both groups, but only the RT+CR group lost lean mass. Adjusted postintervention body- and thigh-composition measures were all lower with RT+CR except intermuscular adipose tissue (IMAT). Knee strength, power, and quality and the 4-m gait speed increased similarly in both groups. Adjusted postintervention means for a 400-m walk time and self-reported disability were better with RT+CR with no group differences in other functional measures, including knee strength. Participants with a lower percentage of fat and IMAT at baseline exhibited a greater improvement in the 400-m walk and knee strength and power.



RT improved body composition (including reducing IMAT) and muscle strength and physical function in obese elderly, but those with higher initial adiposity experienced less improvement. The addition of CR during RT improves mobility and does not compromise other functional adaptations to RT. These findings support the incorporation of RT into obesity treatments for this population regardless of whether CR is part of the treatment.

title: The effects of lifestyle interventions in dynapenic-obese postmenopausal women
abstract: The aim of this study was to investigate the impact of caloric restriction (CR) and resistance training (RT) on body composition, metabolic profile and physical capacity in dynapenic-obese postmenopausal women.  Thirty-eight dynapenic-obese postmenopausal (age, 62.6 ± 4.1 y) women were randomly assigned to one of four groups (1, CR; 2, RT; 3, CR + RT; and 4, control) for a 12-week intervention. The independent variables were body weight, fat mass, and lean body mass (using dual-energy x-ray absorptiometry), waist circumference, fasting lipids and glucose, resting systolic and diastolic blood pressure, and physical capacity (6-min walk, chair stand, and one-leg stand tests).  Body weight, fat mass, and waist circumference decreased similarly in the CR and CR + RT groups (all P ⩽ 0.05). However, only changes in the CR + RT group were significantly different from the control group (all P ⩽ 0.05). Total cholesterol, triglycerides, and systolic and diastolic blood pressure significantly decreased in the CR group (all P ⩽ 0.05); whereas total cholesterol, low-density lipoprotein cholesterol, and systolic blood pressure decreased in the CR + RT group (P ⩽ 0.05). Physical capacity improved significantly in the RT and CR + RT groups (all P ⩽ 0.05), with significant greater improvements in the RT group (P ⩽ 0.05).  Our results suggest that CR with or without RT is effective in improving metabolic profile, whereas RT is effective in improving physical capacity. The combination of RT and CR may be particularly relevant in maximizing improvements in physical capacity in dynapenic-obese postmenopausal women.

title: Resistance training does not contribute to improving the metabolic profile after a 6-month weight loss program in overweight and obese postmenopausal women.
abstract: Limited data are available regarding the impact of caloric restriction (CR) in combination with resistance training (RT) on the metabolic profile of postmenopausal women.



The objective of the study was to determine whether RT adds to CR in improving body composition and the metabolic profile.



This was a 6-month, randomized, clinical trial.



Patients included 107 postmenopausal women (body mass index >27 kg/m(2)).



The intervention was a 6-month CR alone or in combination with a RT program.



Fat mass (FM), lean body mass (LBM), abdominal sc fat and visceral fat, fasting lipids, insulin sensitivity, resting blood pressure, and inflammation markers were measured.



Both groups were similar at baseline and significantly decreased body weight, body mass index, FM, percent FM, abdominal sc fat, and visceral fat after the study (P < 0.001), with greater losses of percent FM and trunk FM in the CR + RT group (P < 0.05). LMB significantly decreased in the CR (-0.9 +/- 2.4 kg) and the CR+RT (-0.4 +/- 2.2 kg) groups (P < 0.005), with no difference between them. Both groups significantly improved plasma triglycerides, fasting insulin level, glucose disposal, and markers of the inflammation profile after weight loss (P < 0.05), with no difference between groups. No improvements were observed for the other variables of interest in both groups.



CR+RT was associated with greater losses in percent FM and trunk FM compared with CR alone. However, CR+RT was not associated with additional improvements in the metabolic profile compared with CR alone.

title: Legacy effects of short-term intentional weight loss on total body and thigh composition in overweight and obese older adults
abstract: Weight regain following intentional weight loss may negatively impact body composition, accelerating fat regain and increasing risk of physical disability. The purpose of this study was to compare long-term changes in whole body and thigh composition in obese older adults who intentionally lost and then partially regained weight to obese older adults who remained weight stable.This pilot study analyzed total body (dual-energy X-ray absorptiometry (DXA)) and thigh (computed tomography (CT)) composition data collected from 24 older (65–79 years) adults 18 months after completion of a 5-month randomized trial that compared resistance training alone (RT) with RT plus caloric restriction (RT+CR).Results:Mean loss of body mass in the RT+CR group (n=13) was 7.1±2.4 kg during the 5-month intervention (74% fat mass; 26% lean mass; all P<0.01), whereas RT (n=11) remained weight stable (+0.3±1.8 kg; P=0.64). Differential group effects were observed for all DXA and CT body composition measures at 5 months (all P⩽0.01); however, by 23 months, group differences persisted only for total body (RT+CR: 81.6±10.0 kg vs RT: 88.5±14.9 kg; P=0.03) and lean (RT+CR: 50.8±9.3 kg vs RT: 54.4±12.0 kg; P<0.01) mass. All RT+CR participants regained weight from 5 to 23 months (mean gain=+4.8±2.6 kg; P<0.01). Total fat mass and all thigh fat volumes increased, whereas thigh muscle volume decreased, during the postintervention follow-up in RT+CR (all P⩽0.01). In the RT group, body mass did not change from 5 to 23 months (−0.2±0.9 kg; P=0.87). Decreased total thigh volume, driven by the loss of thigh muscle volume, were the only postintervention body composition changes observed in the RT group (both P<0.04).Conclusions:Short-term body composition benefits of an RT+CR intervention may be lost within 18 months after completion of the intervention.

title: Changes in lower extremity muscle mass and muscle strength after weight loss in obese men: A prospective study.
abstract: Obesity is not only associated with internal diseases but also with surgical problems. Surgical diseases related to obesity frequently occur in the load bearing joints of the lower limbs. To decrease the occurrence of surgical diseases related to obesity, weight loss has been recommended. It is important for obese men to maintain muscle mass and muscle strength after weight loss because low muscle mass and muscle strength are also related to the occurrence of surgical diseases. To date, the importance of muscle mass and muscle strength after weight loss in obese men has been underappreciated.



The purpose of this study was to investigate changes in lower extremity muscle mass and muscle strength resulting from a weight loss programme consisting of caloric restriction and exercise.



All participants concurrently attended a 12-week diet class 1day/week and a 12-week exercise class 3days/week. Body weight and body composition by dual-energy X-ray absorptiometry and knee extensor strength by dynamometry were assessed.



The weight loss programme led to a 14.1% weight loss accompanied by significant loss of leg muscle mass, static maximal muscle strength, dynamic maximal muscle strength and dynamic muscle endurance but not with significant loss of dynamic muscle power. Decline of muscle strength was related to a decrease in muscle mass, but not completely dependent on a decrease in muscle mass. Body weight-normalised muscle strength increased significantly.



We recommend utilising resistance exercise to restore muscle mass and muscle strength in the legs after substantial weight loss.

title: Impact of resistance training with or without caloric restriction on physical capacity in obese older women
abstract: To investigate the specific impact of resistance training (RT) with or without caloric restriction (CR) on physical capacity in obese older women.  Forty-eight postmenopausal obese women, physically independent and between the ages of 55 and 75 years were recruited. The women were randomly assigned to one of four groups (1: RT [n = 12], 2: CR [n = 12], 3: CR + RT [n = 12], or 4: control group [C; n = 12]) for 3 months. CR and CR + RT groups participated in a weekly group session on nutrition, and RT and CR + RT groups took part in a resistance training program. Physical capacity was measured with 11 different performance tests. A global physical capacity score (range, 0-44) was then computed using quartiles of each test. Body composition was measured by dual-energy x-ray absorptiometry.  Body weight, total fat mass, percentage of fat mass, and body mass index (kg/m2) significantly decreased in the CR and CR + RT groups (P < 0.01), whereas only the CR group showed a significant decrease in lean body mass (P < 0.05) after the 3-month program. The global physical capacity score significantly improved in the RT group (10.0 ± 8.8%; P < 0.01), compared with the C group after 3 months.  Overall, the 3-month RT program alone had a greater effect on physical capacity than CR or CR + RT. Thus, a 3-month RT could help prevent long-term decreases in physical capacity in obese older women.

title: Impact of energy restriction with or without resistance training on energy metabolism in overweight and obese postmenopausal women: a Montreal Ottawa New Emerging Team group study
abstract: present study measured the impact of adding resistance training to an energy-restricted diet on the components of energy expenditure in overweight or obese postmenopausal women. MethodsParticipants (n = 137) were randomly divided into two groups: (1) a diet and resistance training (DRT) group and (2) a diet-only (DO) group. Women followed a 6-month energy-restricted diet consisting of 2,100 to 3,360 kJ less than daily needs. The DRT group also followed a resistance training program (three times a week). Resting energy expenditure (REE) was measured by indirect calorimetry. Total energy expenditure was measured with doubly labeled water. Body composition was measured by dual-energy x-ray absorptiometry. ResultsEighty nine women were included in the analyses for this study (DRT, n = 21; DO, n = 68). REE in both groups was significantly lower after the intervention (mean difference ± SD: DO, −0.26 ± 0.4 MJ d−1; DRT, −0.33 ± 0.4 MJ d−1; P ⩽ 0.05). Relative REE, expressed per kilogram of lean body mass0.856 corrected for fat mass change, remained stable in both groups. Physical activity energy expenditure remained stable in both groups (mean difference ± SD: DO, 0.02 ± 1 MJ d−1, P = 0.91; DRT, −0.14 ± 1 MJ d−1, P = 0.64). ConclusionsAdding resistance training to an energy-restricted diet does not significantly alter any compartment of energy expenditure. REE is lower owing to reduction in body composition compartments, but relative REE is not significantly altered.

title: Resistance weight training during caloric restriction enhances lean body weight maintenance.
abstract: To assess the individual and combined effects of weight loss and weight training on body weight and body composition, 40 obese women were randomly assigned to one of four groups for an 8 wk weight-loss study. These groups were control (C); diet without exercise (DO); diet plus weight training (DPE); and weight training without diet (EO). Body weight decreased for DO (-4.47 kg) and DPE (-3.89 kg) compared with C (-0.38 kg) and EO (0.45 kg). Lean body weight (LBW) increased for EO (1.07 kg) compared with DO (-0.91 kg) and C (-0.31 kg) and for DPE (0.43 kg) compared with DO. Upper-arm muscle areas (determined by radiograph) increased for DPE (11.2 cm2) and EO (10.4 cm2) compared with C (2.7 cm2) and DO (2.1 cm2). It was concluded that weight training results in comparable gains in muscle area and strength for DPE and EO. Adding weight training exercise to a caloric restriction program results in maintenance of LBW compared with DO.

title: Effect of abdominal resistance exercise on abdominal subcutaneous fat of obese women: a randomized controlled trial using ultrasound imaging assessments.
abstract: The aim of this study was to compare the effect of diet and an abdominal resistance training program to diet alone on abdominal subcutaneous fat thickness and waist circumference of overweight and obese women.



This randomized clinical trial included 40 overweight and obese women randomly divided into 2 groups: diet only and diet combined with 12 weeks of abdominal resistance training. Waist and hip circumferences and abdominal skin folds of the subjects were measured at the beginning and 12 weeks after the interventions. In addition, abdominal subcutaneous fat thickness of the subjects was measured using ultrasonography. Percentage body fat and lean body mass of all the subjects were also measured using a bioelectric impedance device.



After 12 weeks of intervention, the weight of participants in both groups decreased; but the difference between the 2 groups was not significant (P = .45). Similarly, other variables including abdominal subcutaneous fat, waist circumference, hip circumference, body mass index, body fat percentage, and skin fold thickness were reduced in both groups; but there were no significant differences between the groups.



This study found that abdominal resistance training besides diet did not reduce abdominal subcutaneous fat thickness compared to diet alone in overweight or obese women.

title: Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study.
abstract: The aim of this study was to test the hypothesis that individual differences in the response of maximal O(2) uptake (VO(2max)) to a standardized training program are characterized by familial aggregation. A total of 481 sedentary adult Caucasians from 98 two-generation families was exercise trained for 20 wk and was tested for VO(2max) on a cycle ergometer twice before and twice after the training program. The mean increase in VO(2max) reached approximately 400 ml/min, but there was considerable heterogeneity in responsiveness, with some individuals experiencing little or no gain, whereas others gained >1.0 l/min. An ANOVA revealed that there was 2.5 times more variance between families than within families in the VO(2max) response variance. With the use of a model-fitting procedure, the most parsimonious models yielded a maximal heritability estimate of 47% for the VO(2max) response, which was adjusted for age and sex with a maternal transmission of 28% in one of the models. We conclude that the trainability of VO(2max) is highly familial and includes a significant genetic component.

title: Home-based resistance training is not sufficient to maintain improved glycemic control following supervised training in older individuals with type 2 diabetes.
abstract: To examine whether improvements in glycemic control and body composition resulting from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training.



We performed a 12-month randomized controlled trial in 36 sedentary, overweight men and women with type 2 diabetes (aged 60-80 years) who were randomly assigned to moderate weight loss plus high-intensity progressive resistance training (RT&WL group) or moderate weight loss plus a control program (WL group). Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. Glycemic control (HbA1c), body composition, muscle strength, and metabolic syndrome abnormalities were assessed at 0, 3, 6, 9, and 12 months.



Compared with the WL group, HbA1c decreased significantly more in the RT&WL group (-0.8%) during 6 months of supervised gymnasium-based training; however, this effect was not maintained after an additional 6 months of home-based training. In contrast, the greater increase in lean body mass (LBM) observed in the RT&WL group compared with the WL group (0.9 kg, P < 0.05) after the gymnasium-based training tended to be maintained after the home-based training (0.8 kg, P = 0.08). Similarly, the gymnasium-based increases in upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months (P < 0.001). There were no between-group differences for changes in body weight, fat mass, fasting glucose, or insulin at 6 or 12 months.



In older adults with type 2 diabetes, home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control. Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control.

title: High-intensity resistance training improves glycemic control in older patients with type 2 diabetes.
abstract: To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes.



Sedentary, overweight men and women with type 2 diabetes, aged 60-80 years (n = 36), were randomized to high-intensity progressive resistance training plus moderate weight loss (RT & WL group) or moderate weight loss plus a control program (WL group). Clinical and laboratory measurements were assessed at 0, 3, and 6 months.



HbA(1c) fell significantly more in RT & WL than WL at 3 months (0.6 +/- 0.7 vs. 0.07 +/- 0.8%, P < 0.05) and 6 months (1.2 +/- 1.0 vs. 0.4 +/- 0.8%, P < 0.05). Similar reductions in body weight (RT & WL 2.5 +/- 2.9 vs. WL 3.1 +/- 2.1 kg) and fat mass (RT & WL 2.4 +/- 2.7 vs. WL 2.7 +/- 2.5 kg) were observed after 6 months. In contrast, lean body mass (LBM) increased in the RT & WL group (0.5 +/- 1.1 kg) and decreased in the WL group (0.4 +/- 1.0) after 6 months (P < 0.05). There were no between-group differences for fasting glucose, insulin, serum lipids and lipoproteins, or resting blood pressure.



High-intensity progressive resistance training, in combination with moderate weight loss, was effective in improving glycemic control in older patients with type 2 diabetes. Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes.

title: Reliability of the PEDro scale for rating quality of randomized controlled trials.
abstract: Assessment of the quality of randomized controlled trials (RCTs) is common practice in systematic reviews. However, the reliability of data obtained with most quality assessment scales has not been established. This report describes 2 studies designed to investigate the reliability of data obtained with the Physiotherapy Evidence Database (PEDro) scale developed to rate the quality of RCTs evaluating physical therapist interventions.



In the first study, 11 raters independently rated 25 RCTs randomly selected from the PEDro database. In the second study, 2 raters rated 120 RCTs randomly selected from the PEDro database, and disagreements were resolved by a third rater; this generated a set of individual rater and consensus ratings. The process was repeated by independent raters to create a second set of individual and consensus ratings. Reliability of ratings of PEDro scale items was calculated using multirater kappas, and reliability of the total (summed) score was calculated using intraclass correlation coefficients (ICC .



The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters. The ICC for the total score was.56 (95% confidence interval=.47-.65) for ratings by individuals, and the ICC for consensus ratings was.68 (95% confidence interval=.57-.76).



The reliability of ratings of PEDro scale items varied from "fair" to "substantial," and the reliability of the total PEDro score was "fair" to "good."

title: Effects of resistance training with moderate vs heavy loads on muscle mass and strength in the elderly: A meta‐analysis
abstract: The purpose of the present study was to perform a meta‐analysis to compare the efficacy of heavy (∼80% of one repetition maximum, 1RM) vs light‐moderate load (∼45% 1RM) resistance training (RT) programs in inducing strength gains and skeletal muscle hypertrophy in elderly people. To assess the role of training volumes, studies in which training protocols were matched for mechanical work were independently analyzed. In all 15 studies included (448 subjects, age 67.8 years), when comparing heavy with light‐moderate loads, strength gains tended to be larger following RT with higher intensities of load, with the resulting total population effect being μ = 0.430 (P = 0.060). Effect sizes were substantially smaller in “work‐matched” studies (μ = 0.297, P = 0.003). Training with higher loads also provoked marginally larger gains in muscle size, although the degree of training‐induced muscle hypertrophy was generally small (0.056 < μ < 0.136). To conclude, provided a sufficient number of repetitions is performed, RT at lower than traditionally recommended intensities of load may suffice to induce substantial gains in muscle strength in elderly cohorts.

title: Activity-related energy expenditure in older adults: a call for more research.
abstract: The purposes of this article were to 1) provide an overview of the science of physical activity-related energy expenditure in older adults (≥65 yr), 2) offer suggestions for future research and guidelines for how scientists should be reporting their results in this area, and 3) present strategies for making these data more accessible to the layperson. This article was meant to serve as a preliminary blueprint for future empirical work in the area of energy expenditure in older adults and translational efforts to make these data useful and accurate for older adults. This document was based upon deliberations of experts involved in the Strategic Health Initiative on Aging Committee of the American College of Sports Medicine. The article was designed to reach a broad audience who might not be familiar with the complexities of assessing energy expenditure, especially in older adults.

title: Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling.
abstract: Caloric restriction decreases skeletal muscle mass in mammals, principally due to a reduction in fiber size. The effect of suboptimal nutrient intake on skeletal muscle metabolic properties in neonatal calves was examined. The longissimus muscle (LM) was collected after a control (CON) or caloric restricted (CR) diet was cosnumed for 8 wk and muscle fiber size, gene expression, and metabolic signal transduction activity were measured. Results revealed that CR animals had smaller (P < 0.05) LM fiber cross-sectional area than CON, as expected. Western blot analysis detected equivalent amounts of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) but reduced (P < 0.05) amounts of the splice-variant, PGC1α-4 in CR LM. Expression of IGF-1, a PGC1α-4 target gene, was 40% less (P < 0.05) in CR than CON. Downstream mediators of autocrine IGF-1 signaling also are attenuated in CR by comparison with CON. The amount of phosphorylated AKT1 was less (P < 0.05) in CR than CON. The ratio of p4EBP1T37/46 to total 4EBP1, a downstream mediator of AKT1, did not differ between CON and CR. By contrast, protein lysates from CR LM contained less (P < 0.05) total glycogen synthase kinase-3β (GSK3β) and phosphorylated GSK3β than CON LM, suggesting blunted protein synthesis. Smaller CR LM fiber size associates with increased (P < 0.05) calpain 1 (CAPN1) activity coupled with lower (P < 0.05) expression of calpastatin, the endogenous inhibitor of CAPN1. Atrogin-1 and MuRF expression and autophagy components were unaffected by CR. Thus CR suppresses the hypertrophic PGC1α-4/IGF-1/AKT1 pathway while promoting activation of the calpain system.

title: Hypoenergetic diet-induced reductions in myofibrillar protein synthesis are restored with resistance training and balanced daily protein ingestion in older men.
abstract: Strategies to enhance weight loss with a high fat-to-lean ratio in overweight/obese older adults are important since lean loss could exacerbate sarcopenia. We examined how dietary protein distribution affected muscle protein synthesis during energy balance (EB), energy restriction (ER), and energy restriction plus resistance training (ER + RT). A 4-wk ER diet was provided to overweight/obese older men (66 ± 4 yr, 31 ± 5 kg/m(2)) who were randomized to either a balanced (BAL: 25% daily protein/meal × 4) or skewed (SKEW: 7:17:72:4% daily protein/meal; n = 10/group) pattern. Myofibrillar and sarcoplasmic protein fractional synthetic rates (FSR) were measured during a 13-h primed continuous infusion of l-[ring-(13)C6]phenylalanine with BAL and SKEW pattern of protein intake in EB, after 2 wk ER, and after 2 wk ER + RT. Fed-state myofibrillar FSR was lower in ER than EB in both groups (P < 0.001), but was greater in BAL than SKEW (P = 0.014). In ER + RT, fed-state myofibrillar FSR increased above ER in both groups and in BAL was not different from EB (P = 0.903). In SKEW myofibrillar FSR remained lower than EB (P = 0.002) and lower than BAL (P = 0.006). Fed-state sarcoplasmic protein FSR was reduced similarly in ER and ER + RT compared with EB (P < 0.01) in both groups. During ER in overweight/obese older men a BAL consumption of protein stimulated the synthesis of muscle contractile proteins more effectively than traditional, SKEW distribution. Combining RT with a BAL protein distribution "rescued" the lower rates of myofibrillar protein synthesis during moderate ER.

title: Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial.
abstract: A dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass (LBM), particularly when combined with exercise.



The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition.



We used a single-blind, randomized, parallel-group prospective trial. During a 4-wk period, we provided hypoenergetic (~40% reduction compared with requirements) diets providing 33 ± 1 kcal/kg LBM to young men who were randomly assigned (n = 20/group) to consume either a lower-protein (1.2 g · kg(-1) · d(-1)) control diet (CON) or a higher-protein (2.4 g · kg(-1) · d(-1)) diet (PRO). All subjects performed resistance exercise training combined with high-intensity interval training for 6 d/wk. A 4-compartment model assessment of body composition was made pre- and postintervention.



As a result of the intervention, LBM increased (P < 0.05) in the PRO group (1.2 ± 1.0 kg) and to a greater extent (P < 0.05) compared with the CON group (0.1 ± 1.0 kg). The PRO group had a greater loss of fat mass than did the CON group (PRO: -4.8 ± 1.6 kg; CON: -3.5 ± 1.4kg; P < 0.05). All measures of exercise performance improved similarly in the PRO and CON groups as a result of the intervention with no effect of protein supplementation. Changes in serum cortisol during the intervention were associated with changes in body fat (r = 0.39, P = 0.01) and LBM (r = -0.34, P = 0.03).



Our results showed that, during a marked energy deficit, consumption of a diet containing 2.4 g protein · kg(-1) · d(-1) was more effective than consumption of a diet containing 1.2 g protein · kg(-1) · d(-1) in promoting increases in LBM and losses of fat mass when combined with a high volume of resistance and anaerobic exercise. Changes in serum cortisol were associated with changes in body fat and LBM, but did not explain much variance in either measure.

title: Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population.
abstract: Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50-65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity.

title: Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice.
abstract: Both caloric restriction (CR) and low-protein, high-carbohydrate (LPHC) ad-libitum-fed diets increase lifespan and improve metabolic parameters such as insulin, glucose, and blood lipids. Severe CR, however, is unsustainable for most people; therefore, it is important to determine whether manipulating macronutrient ratios in ad-libitum-fed conditions can generate similar health outcomes. We present the results of a short-term (8 week) dietary manipulation on metabolic outcomes in mice. We compared three diets varying in protein to carbohydrate ratio under both CR and ad libitum conditions. Ad libitum LPHC diets delivered similar benefits to CR in terms of levels of insulin, glucose, lipids, and HOMA, despite increased energy intake. CR on LPHC diets did not provide additional benefits relative to ad libitum LPHC. We show that LPHC diets under ad-libitum-fed conditions generate the metabolic benefits of CR without a 40% reduction in total caloric intake.

title: mTOR is a key modulator of ageing and age-related disease
abstract: Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of 'when' rather than 'if'. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.

title: Is there a skeletal muscle mass threshold associated with the deterioration of insulin sensitivity in sedentary lean to obese postmenopausal women?
abstract: The purpose of this study was to determine an optimal cut-off point of skeletal muscle mass, using appendicular lean body mass (LBM) index, that identifies at risk individuals with deteriorated insulin sensitivity, using an established quantitative insulin sensitivity index (QUICKI) cut-off.



We performed a cross-sectional analysis in 231 lean and obese (BMI: 18.7-51.0 kg/m(2)) menopausal women. Fasting plasma glucose and insulin were obtained to calculate QUICKI as an index of insulin sensitivity. Skeletal muscle mass was measured as appendicular LBM by DXA and expressed as appendicular LBM index [appendicular LBM (kg)/height (m(2))]. Cut-offs were determined using receiver operating characteristic (ROC) curve analyses.



The best cut-off value for skeletal muscle mass index to identify menopausal women with reduced insulin sensitivity was 7.025 kg/m(2) which had a sensitivity of 69.5% and specificity of 58.2%.



Our results suggest that sedentary postmenopausal women with an appendicular skeletal muscle mass index above 7.025 kg/m(2) may be at greater risk of insulin resistance. Prospective studies are needed to validate our result.

title: Strength Training and the Risk of Type 2 Diabetes and Cardiovascular Disease
abstract: This study aimed to examine the association of strength training with incident type 2 diabetes and cardiovascular disease risk.  We followed 35,754 healthy women (mean age = 62.6 yr, range = 47.0–97.8) from the Women’s Health Study, who responded to a health questionnaire that included physical activity questions in 2000, assessing health outcomes through annual health questionnaire through 2014 (mean ± SD follow-up = 10.7 ± 3.7 yr). Incident type 2 diabetes (N cases = 2120) and cardiovascular disease (N cases = 1742) were confirmed on medical record review. Cases of cardiovascular disease were defined as confirmed cases of myocardial infarction, stroke, coronary artery bypass graft, angioplasty, or cardiovascular disease death.  Compared with women who reported no strength training, women engaging in any strength training experienced a reduced rate of type 2 diabetes of 30% (hazard ratio = 0.70, 95% confidence interval = 0.61–0.80) when controlling for time spent in other activities and other confounders. A risk reduction of 17% was observed for cardiovascular disease among women engaging in strength training (hazard ratio = 0.83, 95% confidence interval = 0.72, 0.96). Participation in both strength training and aerobic activity was associated with additional risk reductions for both type 2 diabetes and cardiovascular disease compared with participation in aerobic activity only.  These data support the inclusion of muscle-strengthening exercises in physical activity regimens for reduced risk of type 2 diabetes and cardiovascular disease, independent of aerobic exercise. Further research is needed to determine the optimum dose and intensity of muscle-strengthening exercises.

title: Exercise-stimulated glucose uptake — regulation and implications for glycaemic control
abstract: Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resistant muscle, emphasizing exercise as a therapeutic cornerstone among patients with metabolic diseases such as diabetes mellitus. Exercise increases uptake of glucose by up to 50-fold through the simultaneous stimulation of three key steps: delivery, transport across the muscle membrane and intracellular flux through metabolic processes (glycolysis and glucose oxidation). The available data suggest that no single signal transduction pathway can fully account for the regulation of any of these key steps, owing to redundancy in the signalling pathways that mediate glucose uptake to ensure maintenance of muscle energy supply during physical activity. Here, we review the molecular mechanisms that regulate the movement of glucose from the capillary bed into the muscle cell and discuss what is known about their integrated regulation during exercise. Novel developments within the field of mass spectrometry-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead.

title: Longitudinal study of muscle strength, quality, and adipose tissue infiltration.
abstract: Sarcopenia is thought to be accompanied by increased muscle fat infiltration. However, no longitudinal studies have examined concomitant changes in muscle mass, strength, or fat infiltration in older adults.



We present longitudinal data on age-related changes in leg composition, strength, and muscle quality (MQ) in ambulatory, well-functioning men and women. We hypothesized that muscle cross-sectional area (CSA) and strength would decrease and muscular fat infiltration would increase over 5 y.



Midthigh muscle, subcutaneous fat (SF), and intermuscular fat (IMF) CSAs and isokinetic leg muscle torque (MT) and MQ (MT/quadriceps CSA) were examined over 5 y in the Health, Aging, and Body Composition study cohort (n = 1678).



Men experienced a 16.1% loss of MT, whereas women experienced a 13.4% loss. Adjusted annualized decreases in MT were 2-5 times greater than the loss of muscle CSA in those who lost weight and in those who remained weight-stable. Weight gain did not prevent the loss of MT, despite a small increase in muscle CSA. Only those who gained weight had an increase in SF (P < 0.001), whereas those who lost weight also lost SF (P < 0.001). There was an age-related increase in IMF in men and women (P < 0.001), and IMF increased in those who lost weight, gained weight, or remained weight-stable (all P < 0.001).



Loss of leg MT in older adults is greater than muscle CSA loss, which suggests a decrease in MQ. Additionally, aging is associated with an increase in IMF regardless of changes in weight or SF.

title: An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia
abstract: Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia.  The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed.  The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%).  The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment.

title: Time-restricted feeding attenuates age-related cardiac decline in Drosophila
abstract: Midnight snacks are bad for the heart Circadian clocks help animals coordinate their active and rest periods with the daily cycles of light and darkness. As anyone who has suffered jet lag or worked night shifts knows, losing this coordination can have deleterious effects. Gill et al. compared fruit flies that were allowed to eat at any time with flies that were only allowed to eat during the day (when they are active). The flies with restricted feeding times slept better and had a slower decline in heart function as they aged. They also showed less weight gain, even though both groups of flies consumed about the same amount. Science, this issue p. 1265 Restricting feeding to daytime has health benefits for fruitflies. Circadian clocks orchestrate periods of rest or activity and feeding or fasting over the course of a 24-hour day and maintain homeostasis. To assess whether a consolidated 24-hour cycle of feeding and fasting can sustain health, we explored the effect of time-restricted feeding (TRF; food access limited to daytime 12 hours every day) on neural, peripheral, and cardiovascular physiology in Drosophila melanogaster. We detected improved sleep, prevention of body weight gain, and deceleration of cardiac aging under TRF, even when caloric intake and activity were unchanged. We used temporal gene expression profiling and validation through classical genetics to identify the TCP-1 ring complex (TRiC) chaperonin, the mitochondrial electron transport chain complexes, and the circadian clock as pathways mediating the benefits of TRF.

title: A Calorie-Restricted Diet Decreases Brain Iron Accumulation and Preserves Motor Performance in Old Rhesus Monkeys
abstract: Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using magnetic resonance imaging, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24, 13 males, 11 females) and standard (n = 17, 8 males, 9 females) diets. Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A Diet × Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

title: Attenuation of sarcopenia by dietary restriction in rhesus monkeys.
abstract: Sarcopenia, the loss of muscle mass with normal aging, devastates quality of life-and related healthcare expenditures are enormous. The prevention or attenuation of sarcopenia would be an important medical advance. Dietary restriction (DR) is the only dietary intervention that consistently extends median and maximum life span, as well as health span in rodents. Evidence suggests that DR will have a similar effect in primates. Furthermore, DR opposes sarcopenia in rodents. We tested the hypothesis that DR will reduce age-related sarcopenia in a nonhuman primate. Thirty adult male rhesus monkeys, half fed a normal calorie intake and half reduced by 30% in caloric intake, were examined over 17 years for changes in dual-energy X-ray absorptiometry-estimated skeletal muscle mass. Body weight-adjusted skeletal muscle mass declined somewhat in both groups but was far more rapid in the control group. We have shown that moderate, adult-onset DR can attenuate sarcopenia in a nonhuman primate model.

title: Interaction between Exercise, Dietary Restriction and Age-Related Bone Loss in a Rodent Model of Male Senile Osteoporosis
abstract: The pathophysiology of age-related bone loss and whether age-related bone loss can be prevented by exercise are still a matter of debate.  It was the aim of this study to investigate the long-term effects of exercise and mild food restriction on bone mineral density (BMD) and bone geometry in the appendicular skeleton of aging male rats.  Male Sprague-Dawley rats were studied from 5 to 23 months of age. The rats were divided into 4 groups: baseline, free access to food and running wheels (RW), fed to pair weight with the RW group (PW) and sedentary control animals with free access to food (SED). All rats were housed individually. Volumetric BMD and geometry of femurs and tibiae were assessed by peripheral quantitative computed tomography (pQCT). In addition, the tibial shafts were analyzed by cortical bone histomorphometry.  At the end of the experiment, RW and PW rats had similar body weight. The body weight of SED rats was 31% greater than that of RW rats. pQCT analysis of femurs and tibiae as well as histomorphometric analysis of the tibial shafts showed that dietary restriction resulted in an enlargement of the marrow cavity and cortical thinning at the femoral and tibial shafts relative to the RW and SED groups. Voluntary running exercise provided no additional protection against age-related bone loss when compared with the 31% heavier SED control rats. Neither exercise nor increased body weight in SED animals could completely prevent age-related bone loss between 19 and 23 months of age.  We conclude that dietary restriction had clear negative effects on BMD and bone geometry and that running wheel exercise provided partial protection but could not prevent age-related bone loss.