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Elevated vascular risk and beta-amyloid (Aβ) burden have been synergistically associated with cognitive decline in preclinical Alzheimer's disease (AD), although the underlying mechanisms remain unclear. We examined whether accelerated longitudinal tau accumulation mediates the vascular risk-Aβ interaction on cognitive decline.We included 175 cognitively unimpaired older adults (age 70.5 ± 8.0 years). Baseline vascular risk was quantified using the office-based Framingham Heart Study general cardiovascular disease risk score (FHS-CVD). Baseline Aβ burden was measured with Pittsburgh Compound-B positron emission tomography (PET). Tau burden was measured longitudinally (3.6 ± 1.5 years) with Flortaucipir PET, focusing on inferior temporal cortex (ITC). Cognition was assessed longitudinally (7.0 ± 2.0 years) using the Preclinical Alzheimer's Cognitive Composite. Linear mixed effects models examined the interactive effects of baseline vascular risk and Aβ on longitudinal ITC tau. Additionally, moderated mediation was used to determine whether tau accumulation mediated the FHS-CVD*Aβ effect on cognitive decline.We observed a significant interaction between elevated baseline FHS-CVD and Aβ on greater ITC tau accumulation (p = 0.004), even in individuals with Aβ burden below the conventional threshold for amyloid positivity. Examining individual vascular risk factors, we found elevated systolic blood pressure and body mass index showed independent interactions with Aβ on longitudinal tau (both p 0.0001). ITC tau accumulation mediated 33% of the interactive association of FHS-CVD and Aβ on cognitive decline.Vascular risks interact with subthreshold levels of Aβ to promote cognitive decline, partially by accelerating early neocortical tau accumulation. Our findings support vascular risk reduction, especially treating hypertension and obesity, to attenuate Aβ-related tau pathology and reduce late-life cognitive decline. ANN NEUROL 2022;92:745-755.

Physical activity (PA) promotes resilience with respect to cognitive decline, although the underlying mechanisms are not well understood. We examined the associations between objectively measured PA and resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) across seven anatomically distributed neural networks.rs-fcMRI, amyloid beta (Aβ) positron emission tomography (PET), PA (steps/day × 1 week), and longitudinal cognitive (Preclinical Alzheimer's Cognitive Composite) data from 167 cognitively unimpaired adults (ages 63 to 90) were used. We used linear and linear mixed-effects regression models to examine the associations between baseline PA and baseline network connectivity and between PA, network connectivity, and longitudinal cognitive performance.Higher PA was associated selectively with greater connectivity in three networks previously associated with cognitive decline (default, salience, left control). This association with network connectivity accounted for a modest portion of PA's effects on Aβ-related cognitive decline.Although other mechanisms are likely present, PA may promote resilience with respect to Aß-related cognitive decline, partly by increasing connectivity in a subset of cognitive networks.

Older adults are encouraged to engage in multicomponent physical activity, which includes aerobic and muscle-strengthening activities. The current work is an extension of the Vitality, Independence, and Vigor in the Elderly 2 (VIVE2) study - a 6-month multicenter, randomized, placebo-controlled trial of physical activity and nutritional supplementation in community dwelling 70-year-old seniors. Here, we examined whether the magnitude of changes in muscle size and quality differed between major lower-extremity muscle groups and related these changes to functional outcomes. We also examined whether daily vitamin-D-enriched protein supplementation could augment the response to structured physical activity. Forty-nine men and women (77 ± 5 yrs) performed brisk walking, muscle-strengthening exercises for the lower limbs, and balance training 3 times weekly for 6 months. Participants were randomized to daily intake of a nutritional supplement (20 g whey protein + 800 IU vitamin D), or a placebo. Muscle cross-sectional area (CSA) and radiological attenuation (RA) were assessed in 8 different muscle groups using single-slice CT scans of the hip, thigh, and calf at baseline and after the intervention. Walking speed and performance in the Short Physical Performance Battery (SPPB) were also measured. For both CSA and RA, there were muscle group × time interactions (P

Background The Lifestyle Interventions and Independence for Elders (LIFE) clinical trial demonstrated that a structured program of physical activity (PA) reduced mobility-disability in older adults by up to 28%. It remains unknown whether the benefits of LIFE PA can be translated to older adults at risk for mobility-disability in real-world community-based settings. To address this knowledge gap, we conducted the ENhancing independence using Group-based community interventions for healthy AGing in Elders (ENGAGE) pilot study and examined the safety, feasibility, and preliminary effectiveness of translating LIFE PA to a community-based senior center. Methods Forty older adults with severe lower extremity functional limitations (age: 76.9 ± 7.3 years; body mass index: 32.7 ± 8 kg/m2; 85% female; short physical performance battery score: 6.3 ± 2.2) were randomized to 24 weeks of PA or a health education control intervention. Results Community-based PA was safe (serious adverse events: PA vs health education, 0:2; nonserious adverse events: PA vs health education, 3:1) and participants successfully adhered to the PA intervention (65.2%). Compared to health education, PA participants who attended ≥25% of scheduled visits had meaningful and sustained short physical performance battery improvements at follow-up (between group short physical performance battery score differences: ~0.7 units). Conclusions ENGAGE has demonstrated the preliminary safety, feasibility, and effectiveness of LIFE PA in a real-world community-based setting. Larger-scale translational studies are needed to further disseminate the benefits of LIFE PA to vulnerable older adults in a variety of community-based settings.

To examine the potential association between serum 25(OH) vitamin D and the performance on the Short Physical Performance Battery (SPPB) including the sub-components; five repeated chair stands test, 4 meters walk test and balance in older mobility-limited community-dwelling men and women.A cross sectional study was performed in American and Swedish subjects who were examined for potential participation in a combined exercise and nutrition intervention trial. Logistic regression analysis and linear regression analyses were performed to evaluate the association for 25(OH)D with the overall score on the SBBP, chair stand, gait speed and balance.Community-dwelling (mean age 77.6 ± 5.3 years) mobility limited American (n=494) and Swedish (n=116) females (59%) and males.The SPPB (0-12 points) includes chair stand (s), gait speed (m/s) and a balance test. Mobility limitation i.e., SPPB score ≤ 9 was an inclusion criterion. A blood sample was obtained to measure serum 25(OH)vitamin D concentrations.No clear association of 25(OH)D with SPPB scores was detected either when 25(OH)D was assessed as a continuous variable or when categorized according to serum concentrations of50, 50-75 or75 nmol/L. However, when analyzing the relationship between 25(OH)D and seconds to perform the chair stands, a significant quadratic relationship was observed. Thus, at serum levels of 25(OH)D above 74 nmol/L, higher concentrations appeared to be advantageous for the chair stand test, whereas for serum levels below 74 nmol/L this association was not observed.This cross- sectional study lacked clear association between serum 25(OH)D and physical performance in mobility limited adults. A potentially interesting observation was that at higher serum levels of 25(OH)D a better performance on the chair stand test was indicated.

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

To describe levels of physical activity among older adults residing at assisted care facilities and their association with physical function. Cross-sectional analysis. Assisted care facilities within the greater Boston, MA area. Older adults aged 65 years and older (N = 65). Physical Activity Level (PAL) as defined by quartiles from accelerometry (counts and steps), Short Physical Performance Battery (SPPB) Score, gait speed, and handgrip strength. Participants in the most active accelerometry quartile engaged in 25 minutes/week of moderate to vigorous physical activity (MVPA) and walked 2,150 steps/day. These individuals had an SPPB score, 400 meter walk speed, and handgrip strength that was 3.7–3.9 points, 0.3–0.4 meters/second, and 4.5–5.1 kg greater respectively, than individuals in the lowest activity quartile, who engaged in less than 5 min/wk of MVPA or took fewer than 460 steps/day. Despite engaging in physical activity levels far below current recommendations (150 min/week of MVPA or > 7000 steps/day), the most active older adults in this study exhibited clinically significant differences in physical function relative to their less active peers. While the direction of causality cannot be determined from this cross-sectional study, these findings suggest a strong association between PAL and physical function among older adults residing in an assisted care facility.

OBJECTIVES: Amyloid-beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at post-mortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer’s disease (AD) remains to be fully elucidated. METHODS: One hundred and thirty-seven older individuals (age=76.3±6.22 years) participating in the Harvard Aging Brain Study underwent Aβ ((11)C-Pittsburgh Compound B) and tau ((18)F-Flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8±1.1). Tau and Aβ PET measures were assessed in regions of interest (ROI) as well as vertex-wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites. RESULTS: Higher levels of Aβ and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical Aβ was associated with higher tau levels in all ROI, independent of age, and very elevated levels of tau were observed primarily in CN with elevated Aβ. A significant interaction between tau and Aβ was observed in both ROI and map level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies. INTERPRETATION: Our results are consistent with the supposition that both Aβ and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD.

OBJECTIVES: Studies show that regular exercise in combination with nutritional support can be effective in managing sarcopenia, which is age-related involuntary loss of skeletal muscle mass and strength. Qualitative investigations of participants’ experiences from interventions in this domain are scarce. In this study, we explored older persons’ experiences from an intervention designed to prevent sarcopenia, with the aim of capturing the participants’ thoughts and opinions. DESIGN: A qualitative study embedded in the multicenter randomized clinical trial The Vitality and Vigor in the Elderly study, VIVE2. Focus group interviews were conducted. Manifest and latent content analyses were performed. PARTICIPANTS: Community dwelling older adults (n=20) 71–86 years of age with minor limitations in mobility. RESULTS: The experiences from the intervention were categorized and interpreted in one overall theme “Feeling more self-confident, cheerful and safe”. The theme encompasses the categories psychological effects of participating in the intervention, physical effects of participating in the intervention, the importance of social support and the importance of a tailored set-up. The participants described their motives for participating in the intervention as being based on concerns regarding the negative health effects of continuing a sedentary lifestyle, difficulties of getting started on their own and lack of confidence in accomplishing change on their own. Participants also expressed that one main objective for participating was to lose weight. CONCLUSION: In this study we have captured the experiences of older adults with minor mobility limitations who participated in a lifestyle intervention. The experiences are interpreted in one overall theme “Feeling more self-confident, cheerful and safe”. The central understanding of the participants’ experiences was that the intervention affected them in several ways, both psychologically and physically, and that supporting factors included the social support, which became a prerequisite for success. A noticeable finding was the discrepancy between the motive of the participants, to lose weight, and the aim of the study, to improve muscle function. The expectation to lose weight seems to reflect what is commonly known as to be healthy. To our knowledge, at least in Sweden, there are no campaigns or public information highlighting the risks of sarcopenia and the complex issue of if, and when weight loss is desirable for older individuals. This finding highlights the importance of providing such information to this target group. The findings in this study provide valuable knowledge for research teams, practitioners and decision makers when designing and setting objectives for health-promoting interventions for older individuals.

PURPOSE OF THE STUDY Older adults are among the most challenging population groups to enroll into health-related research. This article describes two methods used by investigators to recruit mobility limited older adults residing at assisted living or senior housing (SH) facilities into a facility-led exercise-nutrition research study. DESIGN AND METHODS Sedentary older adults were recruited from 42 different assisted living facilities (ALFs) or SH communities. Two different recruitment approaches were used: At 22 sites, investigators conducted heavily advertised informational sessions to recruit participants (Info only). At 20 locations, these sessions were preceded by attendance of a study team member at various activities offered by the facility over the preceding 2 weeks (activity attendance). Population reach, enrollment, personnel cost, and time required to recruit at least five participants at each facility was measured. Reasons for declining participation and withdrawal rate were also measured. RESULTS Sixty percent more residents elected to be screened for eligibility when study personnel attended an activity offered by the facility. Activity attendance resulted in significantly less time, costs, and participant withdrawals compared with facilities with no activity attendance. IMPLICATIONS Study team member attendance at activities offered by senior living facilities reduces cost and duration of recruitment and improves study retention. Interventions targeting this demographic are likely to benefit from deliberately building trust and familiarity among the resident population at senior living communities as part of the recruitment process.

Background Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long-term nutritional supplementation in combination with physical activity in older adults remains unclear. Methods Mobility-limited (short physical performance battery [SPPB] ≤9) and vitamin D insufficient (serum 25(OH) D 9–24 ng/mL) older adults were recruited for this study. All subjects participated in a physical activity program. Subjects were randomized to consume a daily nutritional supplement (150 kcal, 20 g whey protein, 800 IU vitamin D, 119 mL beverage) or placebo (30 kcal, nonnutritive, 119 mL). In a prespecified secondary analysis, we examined total-body composition (dual energy X-ray absorptiometry), thigh composition (computed tomography), and muscle strength, power, and quality before and after the 6-month intervention. Results One hundred and forty-nine subjects were randomized into the study [mean (standard deviation, SD) age 78.5 (5.4) years; 46.3% female; mean (SD) short physical performance battery 7.9 (1.2); mean (SD) vitamin D 18.7 (6.4) ng/mL]. After the intervention period both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation lead to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018). Conclusions Six months of physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in further declines in intermuscular fat and improved muscle density compared to placebo. These results suggest nutritional supplementation provides additional benefits to mobility-limited older adults undergoing exercise training. ClinicalTrials.gov Identifier: NCT01542892

This cluster-randomized trial was designed to determine the efficacy of a 6-month exercise-nutritional supplement program (ENP) on physical function and nutritional status for older adults and the feasibility of implementing this program in a senior living setting. Twenty senior-living facilities were randomized to either a 3 day per week group-based ENP led by a trained facility staff member or a health education program (SAP). Participants (N = 121) completed a short physical performance battery, 400-m walk, handgrip strength test, and mini-nutrition assessment. 25-hydroxyvitamin D [25(OH)D], insulin-like growth-factor 1 (IGF-1), and activity level were also measured. The ENP did not significantly improve physical function or nutritional status compared with the SAP. Compared with baseline, participants in the ENP engaged in 39 min less physical activity per week at 6 months. Several facility characteristics hindered implementation of the ENP. This study highlights the complexity of implementing an evidence-based program in a field setting.

OBJECTIVES: The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). DESIGN: All subjects participated in a physical activity program (3×/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). SETTING: Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. PARTICIPANTS: Mobility-limited (Short Physical Performance Battery (SPPB) ≤9) and vitamin D insufficient (serum 25(OH) D 9 – 24 ng/ml) older adults were recruited for this study. MEASUREMENTS: Primary outcome was gait speed assessed by the 400M walk. RESULTS: 149 subjects were randomized into the study (mean age=77.5±5.4; female=46.3%; mean SPPB= 7.9±1.2; mean 25(OH)D=18.7±6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. CONCLUSION: Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.

Nutritional supplementation and physical activity have been shown to positively influence muscle mass and strength in older adults. The efficacy of long-term nutritional supplementation in combination with physical activity in older adults remains unclear.Mobility-limited (short physical performance battery [SPPB] ≤9) and vitamin D insufficient (serum 25(OH) D 9-24 ng/mL) older adults were recruited for this study. All subjects participated in a physical activity program. Subjects were randomized to consume a daily nutritional supplement (150 kcal, 20 g whey protein, 800 IU vitamin D, 119 mL beverage) or placebo (30 kcal, nonnutritive, 119 mL). In a prespecified secondary analysis, we examined total-body composition (dual energy X-ray absorptiometry), thigh composition (computed tomography), and muscle strength, power, and quality before and after the 6-month intervention.One hundred and forty-nine subjects were randomized into the study [mean (standard deviation, SD) age 78.5 (5.4) years; 46.3% female; mean (SD) short physical performance battery 7.9 (1.2); mean (SD) vitamin D 18.7 (6.4) ng/mL]. After the intervention period both groups demonstrated improvements in muscle strength, body composition, and thigh composition. Nutritional supplementation lead to further losses of intermuscular fat (p = .049) and increased normal muscle density (p = .018).Six months of physical activity resulted in improvements in body composition, subcutaneous fat, intermuscular fat, and strength measures. The addition of nutritional supplementation resulted in further declines in intermuscular fat and improved muscle density compared to placebo. These results suggest nutritional supplementation provides additional benefits to mobility-limited older adults undergoing exercise training. ClinicalTrials.gov Identifier: NCT01542892.

Background Muscle power is a key predictor of physical function in older adults; however, clinically meaningful improvements in leg-extensor muscle power have yet to be identified. The purpose of this study is to establish the minimal clinically important improvement (MCII) and substantial improvement (SI) for leg-extensor power and muscle contraction velocity in mobility-limited older adults. Methods Data were extracted from three randomized trials of leg-extensor muscle power training interventions (3- to 6-month duration). Measurements of leg-extensor power and velocity were obtained using dynamic bilateral leg press at 40% and 70% of the one-repetition maximum. Anchor-based MCIIs were calculated using selected items extracted from the Late Life Function and Disability Instrument. Standard error of measurement and effect size methods were used to calculate the distribution-based MCII. Results Data from 164 participants (mean age: 76.6 ± 5.6 years; Short Physical Performance Battery score: 7.8 ± 1.3) were used in this analysis. The respective MCII and SI estimates for 40% leg-extensor power were 18.3 (9%) and 30.5 (15%) W, and 23.1 (10%) and 41.6 (18%) W for 70% leg-extensor power. The respective MCII and SI estimates for 40% average velocity were 0.03(7%) and 0.08(18%) m/s, and 0.02(6%) and 0.05(15%) m/s for 70% average velocity. Conclusions This is the first study to establish a clinically meaningful improvement of leg-extensor power (9%-10%) and velocity (6%-7%) in mobility-limited older adults. These findings should be used to aid in the design and interpretation of clinical trials and interventions that target improvements in muscle power in this high-risk population.

Nutritional supplementation may potentiate the increase in skeletal muscle protein synthesis following exercise in healthy older individuals. Whether exercise and nutrition act synergistically to produce sustained changes in physical functioning and body composition has not been well studied, particularly in mobility-limited older adults.The VIVE2 study was a multi-center, randomized controlled trial, conducted in the United States and Sweden. This study was designed to compare the effects of a 6-month intervention with a once daily, experimental, 4 fl.oz. liquid nutritional supplement providing 150 kcal, whey protein (20 g), and vitamin D (800 IU) (Nestlé Health Science, Vevey, Switzerland), to a low calorie placebo drink (30 kcal, non-nutritive; identical format) when combined with group-based exercise in 150 community-dwelling, mobility-limited older adults. All participants participated in a structured exercise program (3 sessions/week for 6 months), which included aerobic, strength, flexibility, and balance exercises.The primary outcome was 6-month change in 400 m walk performance (m/s) between supplement and placebo groups. Secondary outcomes included 6 month change in: body composition, muscle cross-sectional area, leg strength, grip strength, stair climb time, quality of life, physical performance, mood/depressive symptoms and nutritional status. These outcomes were selected based on their applicability to the health and well-being of older adults.The results of this study will further define the role of nutritional supplementation on physical functioning and restoration of skeletal muscle mass in older adults. Additionally, these results will help refine the current physical activity and nutritional recommendations for mobility-limited older adults.

Purpose: Low vitamin D level is associated with poor muscle strength in older adults, but little is known about its relationship with muscle power and neuromuscular function in a mobility-limited p...

Lustgarten, MS, Price, LL, Phillips, EM, Kirn, DR, Mills, J, and Fielding, RA. Serum predictors of percent lean mass in young adults. J Strength Cond Res 30(8): 2194-2201, 2016-Elevated lean (skeletal muscle) mass is associated with increased muscle strength and anaerobic exercise performance, whereas low levels of lean mass are associated with insulin resistance and sarcopenia. Therefore, studies aimed at obtaining an improved understanding of mechanisms related to the quantity of lean mass are of interest. Percent lean mass (total lean mass/body weight × 100) in 77 young subjects (18-35 years) was measured with dual-energy x-ray absorptiometry. Twenty analytes and 296 metabolites were evaluated with the use of the standard chemistry screen and mass spectrometry-based metabolomic profiling, respectively. Sex-adjusted multivariable linear regression was used to determine serum analytes and metabolites significantly (p ≤ 0.05 and q ≤ 0.30) associated with the percent lean mass. Two enzymes (alkaline phosphatase and serum glutamate oxaloacetate aminotransferase) and 29 metabolites were found to be significantly associated with the percent lean mass, including metabolites related to microbial metabolism, uremia, inflammation, oxidative stress, branched-chain amino acid metabolism, insulin sensitivity, glycerolipid metabolism, and xenobiotics. Use of sex-adjusted stepwise regression to obtain a final covariate predictor model identified the combination of 5 analytes and metabolites as overall predictors of the percent lean mass (model R = 82.5%). Collectively, these data suggest that a complex interplay of various metabolic processes underlies the maintenance of lean mass in young healthy adults.

The prevalence of overweight and obesity continues to be a major public health concern worldwide. Obesity is a major risk factor for the development of type II diabetes, cardiovascular disease, and increased mortality. Concerns about obesity and overweight among older adults have been far more controversial. The association of overweight and obesity with increased disease burden persists in older adults, and overweight and obesity are also strongly associated with the development of physical disability in this population. However, the efficacy for treatment of obesity in older adults remains an open debate. For obese older adults, who may require weight loss to reduce the risk of cardiometabolic syndrome, weight loss may not be recommended as the associated loss of bone and muscle could leave these individuals at higher risk for frailty and fracture. Thus, optimal strategies for reducing fat mass while preserving bone and muscle mass need to be further evaluated. This chapter will first review the usual age-related changes in skeletal muscle and bone mass with advancing age, the controversy surrounding intentional weight loss in older adults, and discuss the role of diet and physical activity interventions for the successful loss of body fat with specific reference to their effects on bone and skeletal muscle.

Studies aimed at identifying serum markers of cellular metabolism (biomarkers) that are associated at baseline with aerobic capacity (VO₂max) in young, healthy individuals have yet to be reported. Therefore, the goal of the present study was to use the standard chemistry screen and untargeted mass spectrometry (MS)-based metabolomic profiling to identify significant associations between baseline levels of serum analytes or metabolites with VO₂max (77 subjects, age range 18-35 years). Use of multivariable linear regression identified three analytes (standard chemistry screen) and twenty-three metabolites (MS-based metabolomics) containing significant, sex-adjusted associations with VO₂max. In addition, fourteen metabolites were found to contain sex-specific associations with aerobic capacity. Subsequent stepwise multivariable linear regression identified the combination of SGOT, 4-ethylphenylsulfate, tryptophan, γ-tocopherol, and α-hydroxyisovalerate as overall, sex-adjusted baseline predictors of VO₂max (adjusted R(2) = 0.66). However, the results of the stepwise model were found to be sensitive to outliers; therefore, random forest (RF) regression was performed. Use of RF regression identified a combination of seven covariates that explained 57.6 % of the variability inherent in VO₂max. Furthermore, inclusion of significant analytes, metabolites and sex-specific metabolites into a stepwise regression model identified the combination of five metabolites in males and seven metabolites in females as being able to explain 80 and 58 % of the variability inherent in VO₂max, respectively. In conclusion, the evidence presented in the current report is the first attempt to identify baseline serum biomarkers that are significantly associated with VO₂max in young, healthy adult humans.