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Lisa M Roberts,1,2 Byron C Jaeger,3 Liliana C Baptista,1,2 Sara A Harper,1,2 Anna K Gardner,4 Elizabeth A Jackson,5 Dorothy Pekmezi,6 Bhanuprasad Sandesara,4 Todd M Manini,4 Stephen D Anton,4 Thomas W Buford1,2 1Department of Medicine, Division of Gerontology/Geriatrics/Palliative Care, University of Alabama at Birmingham, Birmingham, AL, USA; 2Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 3Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA; 4Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; 5Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA; 6Department of Health Behavior, School of Public Health, the University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Thomas W BufordDepartment of Medicine, Division of Gerontology/Geriatrics/Palliative Care, University of Alabama at Birmingham, 1313 13th Street S., Birmingham, AL 35205, USATel +1 205 996 3008Fax +1 205 996 3110Email twbuford@uabmc.eduBackground: Physical exercise is associated with decreased cardiovascular disease (CVD) risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk older adults.Purpose: This pilot randomized clinical trial aimed to collect critical data on feasibility, safety, and protocol integrity necessary to design a fully powered randomized controlled trial (RCT) and evaluate the impact of combining structured exercise with an intervention designed to enhance non-exercise physical activity (EX+NEPA) compared to EX alone.Methods: Forty participants aged ≥60 years with moderate-to-high risk of coronary heart disease events were randomly assigned to either the EX+NEPA or EX groups and followed for 20 weeks. Both groups underwent a twice-weekly, 8-week center-based exercise intervention with aerobic and resistance exercises. EX+NEPA group also received a wearable activity tracking device along with behavioral monitoring and feedback throughout the study. Study outcomes were evaluated at 8 and 20 weeks.Results: Data are presented as adjusted mean change of the differences over time with 95% confidence intervals at 20 weeks. Relative to EX, the change in steps/day at 20 weeks was 1994 (−40.27, 4028) higher for EX+NEPA. For sedentary time at close-out, the EX+NEPA group was −6.8 (−45.2, 31.6) min/day relative to EX. The between-group differences for systolic and diastolic blood pressure were −9.9 (−19.6, −0.3) and −1.8 (−6.9, 3.3) mmHg, respectively.Conclusion: The addition of wearable technology intervention appeared to positively influence daily activity patterns and changes in blood pressure – potentially improving risk factors for CVD. A fully powered randomized trial is needed to ultimately test this hypothesis.Keywords: aging, cardiovascular, exercise, physical activity, activity monitor

Stephen D Anton1,2, Todd M Manini1, Vanessa A Milsom2, Pamela Dubyak2, Matteo Cesari3, Jing Cheng4, Michael J Daniels5, Michael Marsiske2, Marco Pahor1, Christiaan Leeuwenburgh1, Michael G Perri21Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; 2Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; 3Area di Geriatria, Università Campus Bio-Medico, Rome, Italy; 4Division of Oral Epidemiology and Dental Public Health, San Francisco, CA, USA; 5Department of Statistics, University of Florida, Gainesville, FL, USABackground: 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.Keywords: obesity, weight loss, physical function, oxidative stress, inflammation, walking speed

Abstract We explore the propagation of structured vortex laser beams-shaped light carrying orbital angular momentum (OAM)-through complex multiple scattering medium. These structured vortex beams consist of a spin component, determined by the polarization of electromagnetic fields, and an orbital component, arising from their spatial structure. Although both spin and orbital angular momenta are conserved when shaped light propagates through a homogeneous, low-scattering medium, we investigate the conservation of these angular momenta during the propagation of Laguerre–Gaussian (LG) beams with varying topological charges through a turbid multiple scattering environment. Our findings demonstrate that the OAM of the LG beam is preserved, exhibiting a distinct phase shift indicative of the ‘twist of light’ through the turbid medium. This preservation of OAM within such environments is confirmed by in-house developed Monte Carlo simulations, showing strong agreement with experimental studies. Our results suggest exciting prospects for leveraging OAM in sensing applications, opening avenues for groundbreaking fundamental research and practical applications in optical communications and remote sensing.

Abstract Recent advancements in wavefront shaping techniques have facilitated the study of complex structured light’s propagation with orbital angular momentum (OAM) within various media. The introduction of spiral phase modulation to the Laguerre–Gaussian (LG) beam during its paraxial propagation is facilitated by the negative gradient of the medium’s refractive index change over time, leading to a notable increase in the rate of phase twist, effectively observed as phase retardation of the OAM. This approach attains remarkable sensitivity to even the slightest variations in the medium’s refractive index (∼10 −6). The phase memory of OAM is revealed as the ability of twisted light to preserve the initial helical phase even propagating through the turbid tissue-like multiple scattering medium. The results confirm fascinating opportunities for exploiting OAM light in biomedical applications, e.g. such as non-invasive trans-cutaneous glucose diagnosis and optical communication through biological tissues and other optically dense media.

Abstract This study introduces a novel approach in the realm of liquid biopsies, employing a 3D Mueller-matrix (MM) image reconstruction technique to analyze dehydrated blood smear polycrystalline structures. Our research centers on exploiting the unique optical anisotropy properties of blood proteins, which undergo structural alterations at the quaternary and tertiary levels in the early stages of diseases such as cancer. These alterations manifest as distinct patterns in the polycrystalline microstructure of dried blood droplets, offering a minimally invasive yet highly effective method for early disease detection. We utilized a groundbreaking 3D MM mapping technique, integrated with digital holographic reconstruction, to perform a detailed layer-by-layer analysis of partially depolarizing dry blood smears. This method allows us to extract critical optical anisotropy parameters, enabling the differentiation of blood films from healthy individuals and prostate cancer patients. Our technique uniquely combines polarization-holographic and differential MM methodologies to spatially characterize the 3D polycrystalline structures within blood films. A key advancement in our study is the quantitative evaluation of optical anisotropy maps using statistical moments (first to fourth orders) of linear and circular birefringence and dichroism distributions. This analysis provides a comprehensive characterization of the mean, variance, skewness, and kurtosis of these distributions, crucial for identifying significant differences between healthy and cancerous samples. Our findings demonstrate an exceptional accuracy rate of over $$90\%$$ 90 % for the early diagnosis and staging of cancer, surpassing existing screening methods. This high level of precision and the non-invasive nature of our technique mark a significant advancement in the field of liquid biopsies. It holds immense potential for revolutionizing cancer diagnosis, early detection, patient stratification, and monitoring, thereby greatly enhancing patient care and treatment outcomes. In conclusion, our study contributes a pioneering technique to the liquid biopsy domain, aligning with the ongoing quest for non-invasive, reliable, and efficient diagnostic methods. It opens new avenues for cancer diagnosis and monitoring, representing a substantial leap forward in personalized medicine and oncology.

The primary aim of this study was to test the association of early (first 6 months) adherence related to diet, self-monitoring, and attendance with changes in adiposity and cardiovascular risk factors. This study used data from the 24-month POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for short-and long-term weight loss. A computer tracking system was used to record data on eight indicator variables related to adherence. Using canonical correlations at the 6 and 24 month measurement periods, early behavioral adherence was associated with changes in percent weight loss and waist circumference at 6 months ( R = 0.52) and 24 months ( R = 0.37), but was not associated with cardiovascular disease risk factor levels. Early dietary adherence was associated with changes in insulin at 6 months ( R = 0.19), but not at 24 months ( R = 0.08, ns). Early dietary adherence was not associated with changes in adiposity. [ABSTRACT FROM AUTHOR]

Research on the conceptualization of adherence to treatment has not addressed a key question: Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program. This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for promoting weight loss. A sample of 811 overweight/obese adults was recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of energy); (2) High fat (40%), average protein (15%); (3) Low fat (20%), high protein (25%); (4) High fat (40%), high protein (25%). Throughout the first 6 months of the study, a computer tracking system collected data on eight indicators of adherence. Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses. Two factors (accounting for 66% of the variance) were identified and confirmed: (1) behavioral adherence and (2) dietary adherence. Behavioral adherence did not differ across the four interventions, but prescription of a high fat diet (vs. a low fat diet) was found to be associated with higher levels of dietary adherence. The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional, with two dimensions: behavioral and dietary adherence. [ABSTRACT FROM AUTHOR]

Background: Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested.Methods: Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined.Results: No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance.Conclusions: This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases. [ABSTRACT FROM AUTHOR]

The coefficient of variation (CV) is used to determine sincerity of effort of strength measurements. However, there is a controversy in the literature concerning its validity and effectiveness. We used a meta-analytic approach and calculated the effect size between maximal and submaximal efforts for the CV of grip, elbow flexion and knee extension. We summarized findings concerning stability, sensitivity and specificity of the CV. We found large effect sizes (d >/= 0.8) for all comparisons indicating that submaximal efforts were more variable than maximal efforts. We also found large error rates and low stability of the CV. The error rates and stability values of the CV are unacceptable from both a clinical and a medico-legal standpoint. Therefore, the use of the CV for assessing sincerity of effort needs to be questioned. [ABSTRACT FROM AUTHOR]

Background: Obesity and sedentary lifestyles are prevalent among minority women. This study compared perceived and physiological measures of health in 35 non-Hispanic Black (NHB) and 155 non-Hispanic White (NHW) sedentary women.Methods: Self-perception of body weight, physical shape and appearance, physical fitness, and eating habits were assessed via questionnaire using 10-point scales (1 = poor, 10 = excellent), and height, weight, aerobic capacity (V(O(2))(max)), and 4-day food records were directly measured.Results: Although body mass index (BMI, 30.3 +/- 5.3 vs 27.2 +/- 4.5 kg/m(2)) and weight (82.7 +/- 16.5 vs 73.1 +/- 12.9 kg) were greater (both P = 0.0001) in NHB, groups were similar in self-perception of physical shape and appearance and weight. V(O(2))(max) was lower in NHB compared to NHW (20.7 +/- 4.5 vs 23.5 +/- 4.6 ml x kg(-1) x min(-1), P = 0.002), despite no difference between groups in self-perception of physical fitness. Finally, there was no difference between groups for self-perception of eating habits and percentage of calories derived from fat (%fat). The results were unchanged after adjusting for age, education, and income, except that %fat was greater in NHB compared to NHW (35.7 +/- 6.3 vs 33.8 +/- 6.9%, P = 0.03).Conclusions: Although NHB were heavier, more obese, less fit, and consumed a greater %fat than NHW, they perceived their weight, physical shape and appearance, physical fitness, and eating habits to be no worse than those of their White counterparts. The perceptions of NHB regarding their weight, fitness, and eating habits may represent barriers to change. [ABSTRACT FROM AUTHOR]

Study Objectives: The purpose of this study was to determine the impact of a pretransplantation determination of body mass index (BMI) on survival after lung transplantation.Design and Patients: Univariate and multivariate survival analyses of a single institution database consisting of 85 patients who had undergone lung transplantations between March 1994 and October 1998.Setting: University of Florida Health Science Center.Results: Kaplan-Meier survival curves showed that patients who were obese (ie, BMI, > or = 30) at a pretransplantation assessment had a marked decrease in posttransplantation survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression model revealed that the most powerful predictors of mortality after lung transplantation were higher pretransplantation BMI and the development of obliterative bronchiolitis.Conclusions: Our results suggest that the posttransplantation risk for mortality is possibly three times greater for obese patients than for nonobese patients. Additional study is needed to identify the mechanisms for such higher risk in obese patients. Our data also suggest that transplantation centers should not routinely reject underweight patients (ie, BMI, < 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung transplantation listing solely on the basis of weight, as their outcomes may not be significantly different than patients with normal BMIs. [ABSTRACT FROM AUTHOR]

Laser speckle imaging (LSI) is a well-known and useful approach for the non-invasive visualization of flows and microcirculation localized in turbid scattering media, including biological tissues (such as brain vasculature, skin capillaries etc.). Despite an extensive use of LSI for brain imaging, the LSI technique has several critical limitations. One of them is associated with inability to resolve a functionality of vessels. This limitation also leads to the systematic error in the quantitative interpretation of values of speckle contrast obtained for different vessel types, such as sagittal sinus, arteries, and veins. Here, utilizing a combined use of LSI and fluorescent intravital microscopy (FIM), we present a simple and robust method to overcome the limitations mentioned above for the LSI approach. The proposed technique provides more relevant, abundant, and valuable information regarding perfusion rate ration between different types of vessels that makes this method highly useful for in vivo brain surgical operations.

The decomposition of the Mueller matrix of blood films has been carried out using differential matrices with polarized and depolarized parts. The use of a coherent reference wave is applied and the algorithm of digital holographic reconstruction of the field of complex amplitudes is used. On this basis, the 3D Mueller-matrix diffuse tomography method—the reconstruction of distributions of fluctuations of linear and circular birefringence of depolarizing polycrystalline films of human blood is analytically justified and experimentally tested. The dynamics of the change in the magnitude of the statistical moments of the first-fourth order, which characterize layer-by-layer distributions of fluctuations in the phase anisotropy of the blood film, is examined and analyzed. The most sensitive parameters for prostate cancer are the statistical moments of the third and fourth orders, which characterize the asymmetry and kurtosis of fluctuations in the linear and circular birefringence of blood films. The excellent accuracy of differentiation obtained polycrystalline films of blood from healthy donors and patients with cancer patients was achieved.

OBJECTIVE: This study tested a secondary hypothesis of the CALERIE trial (Heilbronn et al., 2006) that a 12-month period of intentional dietary restriction would be associated with an increase in eating disorder symptoms. DESIGN: To test this hypothesis, 48 overweight adults were randomly assigned to four treatment arms in a 12-month study: (1) 25% calorie restriction, (2) 12.5% calorie restriction and 12.5% increased energy expenditure by structured exercise, (3) low-calorie diet, and (4) healthy diet (no-calorie restriction). MAIN OUTCOME MEASURES: Primary outcome measures for the study were changes in: eating disorder symptoms, mood, dietary restraint, body weight, and energy balance. RESULTS: All three dietary restriction arms were associated with increased dietary restraint and negative energy balance, but not with increased ED symptoms or other harmful psychological effects. Participants in the three calorie restriction arms lost significant amounts of body weight. The psychological and behavioral effects were maintained during a 6-month follow-up period. CONCLUSION: These results did not support the hypothesis that caloric restriction causes increased eating disorder symptoms in overweight adults. In general, caloric restriction had either benign or beneficial psychological and behavioral effects. Copyright © 2008 by the American Psychological Association, Inc. [ABSTRACT FROM AUTHOR]

Objectives: The study was conducted to explore associations between markers of mitochondrial quality control (MQC) from vastus lateralis muscle biopsies, serum inflammatory markers, and measures of muscle power assessed by two different tools in a sample of older adults., Design: Secondary analysis of data collected in the PeppeR develOpMental ProjecT (PROMPT) at the University of Florida (Gainesville, FL, USA)., Methods: Forty-three older adults (n = 20 women) were included in the study. Muscle volume of the calf and thigh was quantified by three-dimensional magnetic resonance imaging. Lower-limb muscle power was estimated using 5-time sit-to-stand (5STS) muscle power equations and isokinetic test. Protein markers of MQC were measured in muscle samples by Western immoblotting (n = 12-23), while type I and II fiber cross-sectional area (CSA) and their proportion were quantified using immunohistochemistry (n = 12). Cytochrome C oxidase enzyme activity was measured spectrophotometrically. Finally, inflammatory markers were quantified in the serum using a multiplex immunoassay (n = 39)., Results: Mean age of participants was 78.1 ± 5.5 years, and the average body mass index was 26.2 ± 4.5 kg/m 2 . Markers of mitochondrial biogenesis (i.e., PGC-1α), mitochondrial import proteins (i.e., cHsp70 and mtHsp70), and type I fiber CSA were significantly associated with muscle power estimated via both 5STS muscle power equations and isokinetic test (p < 0.05). Specific associations were also found according to the muscle power assessment method. 5STS muscle power measures were negatively correlated with ClvCasp3, P-AMPK, T-AMPK, P-p38, GM-CSF, INF-γ, IL1b, IL6, IL8, and TNF-α, whereas positive associations were found with BAX (p < 0.05). In contrast, isokinetic measures were significantly and positively correlated with RIP140, Hsp60, and type II muscle fiber CSA (p < 0.05)., Conclusions: Markers of mitochondrial biogenesis (PGC-1α), mitochondrial import proteins (cHsp70 and mtHsp70), and type I muscle fiber CSA were significantly linked to lower-limb muscle power in older adults. These results suggest that muscle power is influenced by mitochondrial signaling. We also found that the relationship between mitochondrial mediators, inflammatory markers, and muscle power varied according to the assessment tool used., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study, collection, analyses, or interpretation of data, writing of the manuscript, or decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: While sepsis, an exaggerated response to infection, can affect people of all age groups, it is more prevalent in middle-aged and older adults. Older adults suffer worse short-term and long-term outcomes than younger patients. Older sepsis survivors are commonly discharged to long-term acute care facilities, where they often die within 1 year. Those who return home from the hospital lose the momentum of physical function improvement after early inpatient rehabilitation, and often face exacerbation of comorbidities and decline in physical function. Additionally, patients who are discharged home often live at distant locations and are not able to commute to rehabilitation centers due to their poor health status. Therefore, remotely delivered exercise interventions tailored to this population hold promise to improve physical function safely and effectively after sepsis. However, this type of intervention has yet to be tested in this population., Objective: This study aims to assess the safety, feasibility, and ease of recruitment and retention of participants for a remotely delivered physical activity intervention for improving physical function in middle-aged and older sepsis survivors., Methods: The proposed intervention will be delivered through a digital health platform that comprises a patient-facing mobile app and a 12-week physical activity program specifically designed for middle-aged and older sepsis survivors with poor health status who may face challenges participating in traditional out-patient or community-based exercise interventions. This study is ongoing and plans to enroll 40 sepsis survivors aged 55 years and older who will be randomized to either a remotely delivered exercise intervention group or a control group (electronic health diary). Both groups will use a tablet containing the Health in Motion app (Blue Marble Health). The intervention group will receive a clinician-designed personalized avatar-guided home exercise program and reminders while the control group will self-report daily activities using the in-app health diary feature., Results: This study is the first to use a home-based, remotely monitored 12-week exercise program to improve physical function in sepsis survivors. This study will evaluate the safety, feasibility, and efficacy, providing the necessary knowledge to design and calculate power for future larger trials., Conclusions: This study will provide important information for planning a future randomized clinical trial to test the efficacy of a remotely delivered exercise intervention in this high-risk population., Trial Registration: ClinicalTrials.gov NCT05568511; https://clinicaltrials.gov/study/NCT05568511., International Registered Report Identifier (irrid): DERR1-10.2196/60270., (©Rola S Zeidan, Margaret K Ohama, Natalia Evripidou, Stephen D Anton, Laith L Hamed, Yi Lin, Christiaan Leeuwenburgh, Faheem W Guirguis, Philip A Efron, Sheryl Flynn, Barbara Smith, Rhonda Bacher, Naveen Bakarasan, Juan Sarmiento Delgado, Robert T Mankowski. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 17.10.2024.)

Purpose: Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite associated with cardiovascular disease (CVD). In preclinical and observational studies, resveratrol and exercise training have been suggested as potential strategies to reduce the systemic levels of TMAO. However, evidence from experimental studies in humans remains unknown. This project examined the dose-dependent effects of a combined resveratrol intervention with exercise training on circulating TMAO and other related metabolite signatures in older adults with high CVD risk., Methods: Forty-one older adults [mean (±SD) age of 72.1 (6.8) years] participated in a 12-week supervised center-based, multi-component exercise training intervention [2×/week; 80 min/session] and were randomized to one of two resveratrol dosages [Low: 500 vs. High:1000 mg/day] or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes., Results: After the 12-week intervention, TMAO concentration increased over time, regardless of treatment [mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04]. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers [|r| > 0.4, p < 0.05]., Conclusion: These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Time-restricted eating (TRE), a dietary pattern reducing the duration of daily food consumption, has recently gained popularity. Existing studies show the potential benefits of TRE for cardiometabolic health. Uncertainty remains about whether these benefits are solely from altered meal timing or influences on other health behaviors, including sleep. Despite growing scientific interest in the effects of TRE on sleep parameters, the topic has not been systematically explored., Methods: This review examined the effects of TRE interventions (daily fasting duration ≥14 h) lasting at least 8 weeks on objective and subjective sleep parameters. Six randomized control trials were identified through Pubmed, Embase, Google Scholar, and Scopus through September 2023., Results: Of the included studies, three employed objective sleep measures using wearables and five studies assessed sleep subjectively through self-report questionnaires. Only one study reported significant improvements in subjective sleep quality following a TRE intervention. Additionally, one study found significant decreases in sleep duration, two studies found significant decreases in sleep efficiency, and one found significant increases in sleep onset latency., Discussion: Current evidence indicates that short to mid-term TRE does not typically worsen sleep parameters. However, some populations may experience reduced sleep disturbances, while others may experience reductions in sleep efficiency. Longer duration studies with objective sleep assessments are needed to better understand the effects of TRE on sleep parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bohlman, McLaren, Ezzati, Vial, Ibrahim and Anton.)

Objective: A growing body of evidence has supported the health benefits of extended daily fasting, known as time-restricted eating (TRE); however, whether the addition of TRE enhances the known benefits of calorie restriction (CR) remains unclear., Methods: PubMed, Scopus, the Cochrane Library, and Google Scholar were searched through April 2023. This systematic review includes randomized controlled trials (RCTs) that compared CR + TRE with CR alone in energy-matched conditions of at least 8 weeks in duration that assessed changes in body weight and cardiometabolic disease risk factors in adults with overweight and/or obesity., Results: Seven studies were identified (n = 579). Two studies reported greater weight loss and reductions in diastolic blood pressure with CR + TRE compared with CR alone after 8 to 14 weeks, whereas one study reported greater improvements in triglycerides and glucose tolerance with CR + TRE (3 days/week) compared with CR alone following 26 weeks. One study reported significant increases in homeostatic model assessment of insulin resistance (HOMA-IR) levels with CR + TRE versus CR alone after 8 weeks. There were no statistically significant differences in any other outcome variable between the two interventions., Conclusions: The addition of TRE to CR regimens resulted in greater weight loss and improvements in cardiometabolic risk factors in some studies; however, the majority of studies did not find additional benefits., (© 2024 The Obesity Society.)

Background: The objective was to test the efficacy of a scalable, virtually delivered, diabetes-tailored weight management program on glycemic control in adults with type 2 diabetes (T2D)., Methods: This was a single arm, three-site clinical trial. Participants had baseline HbA1c between 7-11% and BMI between 27-50 kg/m 2 . Primary outcome was change in HbA1c at 24 weeks. Secondary outcomes were changes in body weight, waist circumference, the Diabetes Distress Scale (DDS), quality of life (IWQOL-L), and hunger (VAS). Generalized linear effects models were used for statistical analysis., Results: Participants (n = 136) were 56.8 ± 0.8 y (Mean ± SEM), 36.9 ± 0.5 kg/m 2 , 80.2% female, 62.2% non-Hispanic white. Baseline HbA1c, weight, and total DDS score were 8.0 ± 0.09%, 101.10 ± 1.47 kg, and 2.35 ± 0.08, respectively. At week 24, HbA1c, body weight, and total DDS decreased by 0.75 ± 0.11%, 5.74 ± 0.50%, 0.33 ± 0.10 units, respectively (all p < 0.001). Also, at week 24, quality of life increased by 9.0 ± 1.2 units and hunger decreased by 14.3 ± 2.4 units, (both p < 0.0001)., Conclusions: The scalable, virtually delivered T2D-tailored weight management program had favorable and clinically meaningful effects on glycemic control, body weight, and psychosocial outcomes., (© 2023. The Author(s).)

Objectives: There is uncertainty about effects of physical activity on physical performance, such as gait speed, among community-dwelling older adults according to their physical frailty status. We determined whether a long-term, moderate-intensity physical activity program was associated with different responses on gait speed over 4 m and 400 m based on physical frailty status., Design: Post hoc analysis from the Lifestyle Interventions and Independence for Elders (LIFE) (NCT01072500), a single-blind randomized clinical trial testing the effect of physical activity intervention compared with health education program., Setting and Participants: We analyzed data on 1623 community-dwelling older adults (78.9 ± 5.2 years) at risk for mobility disability., Methods: Physical frailty was assessed at baseline using the Study of Osteoporotic Fractures frailty index. Gait speed over 4 m and 400 m was measured at baseline, and 6, 12, and 24 months., Results: We estimated significantly better 400-m gait speed at 6, 12, and 24 months for nonfrail older adults in the physical activity group, but not for frail participants. Among frail participants, physical activity showed a potentially clinically meaningful benefit on 400-m gait speed at 6 months (0.055; 95% CI 0.016-0.094; P = .005), compared with the healthy educational intervention, only in those who, at baseline, were able to rise from a chair 5 times without using their arms., Conclusions and Implications: A well-structured physical activity program produced a faster 400-m gait speed potentially able to prevent mobility disability among physically frail individuals with preserved muscle strength in lower limbs., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Interleukin (IL)-6 is a well-accepted biomarker of chronic low-grade inflammation possibly conditioning the effect of physical activity (PA) intervention on physical performance in mobility-limited older adults. We evaluated PA intervention effects on 400 m gait speed by yearly change of IL-6 levels in a post-hoc analysis from Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter single-blind randomized clinical trial on 1300 sedentary older adults (mean age:78.85 ± 5.23,65.85 % women) at risk for mobility disability. We compared the intervention effects on 400 m gait speed at 12 months follow-up, according to yearly IL-6 change categorized for 1 pg/ml increase or decrease, and subsequently for larger range of yearly variation. Among subjects with yearly IL-6 change between -1 and + 2 pg/ml, we observed a significant difference of gait speed in PA intervention group compared to healthy educational intervention group [0.041 m/s,95 % confidence interval (CI):0.008-0.074,p = 0.006;Cohen's d:0.26, 95 % CI:0.12-0.41). No effects were observed on 400 m gait speed for wider range of variation of plasma IL-6 levels. Limiting change of IL-6 levels under this specific hormetic window could be an important goal to achieve better benefit from PA intervention in terms of gait speed change and prevention of mobility disability., Competing Interests: Competing interest No conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history., Methods: We used cohort data from the 1999-2006 and 2011-2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m 2 , women <5.45 kg/m 2 ). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM., Results: The mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31-2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14-4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98-1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75-1.93) mortality were not statistically significant in the matched cohort., Conclusion: Cancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Altered mitochondrial quality and function in muscle may be involved in age-related physical function decline. The role played by the autophagy-lysosome system, a major component of mitochondrial quality control (MQC), is incompletely understood. This study was undertaken to obtain initial indications on the relationship between autophagy, mitophagy, and lysosomal markers in muscle and measures of physical performance and lower extremity tissue composition in young and older adults. Twenty-three participants were enrolled, nine young (mean age: 24.3 ± 4.3 years) and 14 older adults (mean age: 77.9 ± 6.3 years). Lower extremity tissue composition was quantified volumetrically by magnetic resonance imaging and a tissue composition index was calculated as the ratio between muscle and intermuscular adipose tissue volume. Physical performance in older participants was assessed via the Short Physical Performance Battery (SPPB). Protein levels of the autophagy marker p62, the mitophagy mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), the lysosomal markers transcription factor EB, vacuolar-type ATPase, and lysosomal-associated membrane protein 1 were measured by Western immunoblotting in vastus lateralis muscle biopsies. Older adults had smaller muscle volume and lower tissue composition index than young participants. The protein content of p62 and BNIP3 was higher in older adults. A negative correlation was detected between p62 and BNIP3 and the tissue composition index. p62 and BNIP3 were also related to the performance on the 5-time sit-to-stand test of the SPPB. Our results suggest that an altered expression of markers of the autophagy/mitophagy-lysosomal system is related to deterioration of lower extremity tissue composition and muscle dysfunction. Additional studies are needed to clarify the role of defective MQC in human muscle aging and identify novel biological targets for drug development.

Background: Natural dietary compounds that can modulate the inflammation process have the potential to improve physical function through a number of biological pathways, and thus may represent an alternative approach to avert functional decline compared to more time-burdening lifestyle interventions. In this pilot trial, we tested the feasibility and explored the effect of a nutritional compound, Curcumin C3 Complex® for improving physical function and muscle strength in moderately functioning older adults with low-grade inflammation., Methods: Moderately functioning (short physical performance battery, SPPB <10) and sedentary older adults (>65 years) with low-grade systemic inflammation (c-reactive protein >1mg/dL) were randomized to receive Curcumin C3 Complex® (n=9) (1000mg/day) or placebo (n=8) groups for 12 weeks. All participants (age range: 66-94 years, 8 females and 9 males) underwent functional testing (SPPB and walking speed by the 400-meter walk test) and lower-limb strength (knee flexion and extension peak torque by the Biodex test) at baseline and 12 weeks. Venous blood was collected at baseline, 4, 8 and 12 weeks for safety blood chemistry analyses and biomarkers of inflammation., Results: A total of 17 participants were randomized and completed the study. Adherence was high (> 90%) and there were no adverse events reported or abnormal blood chemistries reported. Based on effect sizes, participants in the Curcumin C3 Complex® group demonstrated large effect sizes in the SPPB (Cohen's effect size d=0.75) and measures of knee extension (d=0.69) and flexion peak torque (d=0.82). Effect sizes for galectin-3 (d=-0.31) (larger decrease) and interleukin-6 (d=0.38) (smaller increase) were small in the Curcumin C3 Complex® group compared to placebo., Conclusion: This pilot trial suggests that there were no difficulties with recruitment, adherence and safety specific to the study protocol. Preliminary findings warrant a Phase IIb clinical trial to test the effect of Curcumin C3 Complex® on physical function and muscle strength in older adults at risk for mobility disability., Competing Interests: none.

The prevalence of obesity is higher among Black women (56.6%) compared to Hispanic women (50%) and non-Hispanic White women (42%). Notably, interventions to reduce obesity typically result in initial weight loss that is not maintained. This study tested (a) the effectiveness of a 6-month Health-Smart Weight Loss (HSWL) Program for Black women patients with obesity implemented by community health workers (CHWs) within primary care clinics and (b) the comparative effectiveness of two 12-month physician-implemented weight loss maintenance programs-a Patient-Centred Culturally Sensitive Weight Loss Maintenance Program (PCCS-WLM Program) and a Standard Behavioural Weight Loss Maintenance Program (SB-WLM Program). Black women patients (N = 683) with obesity from 20 community primary care clinics participated in the HSWL Program and were then randomized to either maintenance program. The HSWL Program led to significant weight loss (i.e., 2.7 pounds, 1.22 kg, p < .01, -1.1%) among the participants. Participants in both the PCCS-WLM Program and the SB-WLM Program maintained their weight loss; however, at month 18, participants in the PCCS-WLM Program had a significantly lower weight than those in the SB-WLM (i.e., 231.9 vs. 239.4 pounds or 105.19 vs. 108.59 kg). This study suggests that (a) the HSWL Program can produce significant weight loss among Black women patients with obesity when implemented in primary care clinics by CHWs, and (b) primary care physicians can be trained to successfully promote weight loss maintenance among their Black women patients., (© 2022 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited., Methods: A total of 2050 older adults (≥60 years old) surviving for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999-2014) were included for analysis. The exposure variable, a 45-item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 [fit], 0.10 < FI ≤ 0.21 [prefrail], and FI > 0.21 [frail]). All-cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose-response curves., Results: For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person-years for FI ≤ 0.10, 3.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 7.5 per 100 person-years for FI > 0.21) had higher mortality than their cancer-free counterparts (1.4 per 100 person-years for FI ≤ 0.10, 2.4 per 100 person-years for 0.10 < FI ≤ 0.21, and 5.4 per 100 person-years for FI > 0.21). The multivariable model suggested a positive association between the FI and all-cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73-4.53) and participants without a cancer history (aHR for FI > 0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29-3.32). Restricted cubic splines indicated that all-cause mortality risk increased with the FI in a monotonic pattern., Conclusions: Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history., (© 2022 American Cancer Society.)

Time-restricted eating (TRE), a popular form of intermittent fasting, has been demonstrated to provide multiple health benefits, including an extension of healthy lifespan in preclinical models. While the specific mechanisms remain elusive, emerging research indicates that one plausible mechanism through which TRE may confer health benefits is by influencing the expression of the epigenetic modulator circulatory miRNAs, which serve as intercellular communicators and are dysregulated in metabolic disorders, such as obesity. Therefore, the goal of this pilot study is to examine the effects of a 4-week TRE regimen on global circulatory miRNA from older (≥65 years) overweight participants. Pre- and post-TRE regimen serum samples from nine individuals who participated in the Time to Eat clinical trial (NCT03590847) and had a significant weight loss (2.6 kg, p < 0.01) were analyzed. The expressions of 2083 human miRNAs were quantified using HTG molecular whole transcriptome miRNA assay. In silico analyses were performed to determine the target genes and biological pathways associated with differentially expressed miRNAs to predict the metabolic effects of the TRE regimen. Fourteen miRNAs were differentially expressed pre- and post-TRE regimen. Specifically, downregulated miRNA targets suggested increased expression of transcripts, including PTEN, TSC1, and ULK1, and were related to cell growth and survival. Furthermore, the targets of downregulated miRNAs were associated with Ras signaling (cell growth and proliferation), mTOR signaling (cell growth and protein synthesis), insulin signaling (glucose uptake), and autophagy (cellular homeostasis and survival). In conclusion, the TRE regimen downregulated miRNA, which, in turn, could inhibit the pathways of cell growth and activate the pathways of cell survival and might promote healthy aging. Future mechanistic studies are required to understand the functional role of the miRNAs reported in this study.

Background: Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in (i) older (vs young) adults and (ii) older CCI (vs older RAP) patients to gain insight into underlying pathobiology of CCI in older adults., Method: Prospective longitudinal study with young (≤45 years) and older (≥65 years) septic adults, who were characterized by (i) baseline predisposition, (ii) hospital outcomes, (iii) serial Sequential Organ Failure Assessment (SOFA) organ dysfunction scores over 14 days, (iv) Zubrod Performance status at 3-, 6-, and 12-month follow-up, and (v) mortality over 12 months, was conducted. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS., Results: Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status, and mortality over 12 months. Additionally, older (vs young) and older CCI (vs older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism, and antiangiogenesis over 14 days after sepsis., Conclusion: Older (vs young) and older CCI (vs older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vitamin D insufficiency contributes to muscle weakness and a higher risk of falls in older adults., Objectives: This study explored the impact of vitamin D supplementation on self-reported falls and physical function in older adults with low vitamin D levels and a recent fall history., Materials and Methods: Twenty-five older adults ≥ 70 years with two or more falls during the past year, low vitamin D blood levels (≥10 ng/ml and < 30 ng/mL), and slow gait speed (1.2 m/s) participated in a 6-month vitamin D supplementation (800 IU/day) study. A modified version of the Morse Fall Scale questionnaire was used to assess frequency of falls over one-year prior to study enrollment. Functional outcomes (short physical performance battery, handgrip strength, gait Timed Up and Go, and six-minute walk), and vitamin D levels were assessed at baseline and 6-month follow-up., Results: Based on diaries and pill counts, participants were generally adherent to the intervention (6 of 7 days per week). Supplementation with 800 IU/day of vitamin D for 6 months increased blood vitamin D levels from 23.25±4.8 ng/ml to 29.13±6.9 ng/ml (p<0.001). Self-reported number of falls decreased from an average of 3.76 ± 2.2 falls in one-year to 0.76 plusmn; 1.4 falls (p <0.0001) over the 6-month intervention. No changes in functional outcome measures were observed., Conclusions: Vitamin D supplementation at the currently recommended dose of 800 IU/day increased blood vitamin D levels and reduced frequency of falls in older adults with low vitamin D levels and a recent fall history., Competing Interests: The authors declare no conflict of interest.

Background: Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile., Methods: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0 m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community-dwelling high-functioning older adults (Health ABC) with 2 trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk., Results: We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13-1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12-1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10-1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12-2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85-1.66)., Conclusions: High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Spexin (SPX) is a 14-amino acid neuropeptide, discovered recently using bioinformatic techniques. It is encoded by the Ch12:orf39 gene that is widely expressed in different body tissues/organs across species, and secreted into systemic circulation. Recent reports have highlighted a potentially important regulatory role of SPX in obesity and related comorbidities. SPX is also ubiquitously expressed in human tissues, including white adipose tissue. The circulating concentration of SPX is significantly lower in individuals with obesity compared to normal weight counterparts. SPX's role in obesity appears to be related to various factors, such as the regulation of energy expenditure, appetite, and eating behaviors, increasing locomotion, and inhibiting long-chain fatty acid uptake into adipocytes. Recent reports have also suggested SPX's relationship with novel biomarkers of cardiovascular disease (CVD) and glucose metabolism and evoked the potential role of SPX as a key biomarker/player in the early loss of cardiometabolic health and development of CVD and diabetes later in life. Data on age-related changes in SPX and SPX's response to various interventions are also emerging. The current review focuses on the role of SPX in obesity and related comorbidities across the life span, and its response to interventions in these conditions. It is expected that this article will provide new ideas for future research on SPX and its metabolic regulation, particularly related to cardiometabolic diseases., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Aging-related changes to biological structures such as cardiovascular and musculoskeletal systems contribute to the development of comorbid conditions including cardiovascular disease and frailty, and ultimately lead to premature death. Although, frail older adults often demonstrate both cardiovascular and musculoskeletal comorbidities, the etiology of sarcopenia, and especially the contribution of cardiovascular aging is unclear. Aging-related vascular calcification is prevalent in older adults and is a known risk factor for cardiovascular disease and death. The effect vascular calcification has on function during aging is not well understood. Emerging findings suggest vascular calcification can impact skeletal muscle perfusion, negatively affecting nutrient and oxygen delivery to skeletal muscle, ultimately accelerating muscle loss and functional decline. The present review summarizes existing evidence on the biological mechanisms linking vascular calcification with sarcopenia during aging., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the safety and feasibility of combining exercise (EX) and resveratrol to treat older adults with physical function limitations., Methods: Three-arm, two-site pilot randomized, controlled trial (RCT) for community-dwelling adults (N = 60), 71.8 ± 6.3 years of age with functional limitations. Participants were randomized to receive either 12 weeks of (1) EX + placebo [EX0], (2) EX + 500 mg/day resveratrol [EX500], or (3) EX + 1000 mg/day resveratrol [EX1000]. EX consisted of two sessions a week for 12 weeks of center-based walking and whole-body resistance training. Safety was assessed through adverse events and feasibility through exercise session and supplement (placebo, or resveratrol) protocol adherence. Outcome measures included a battery of indices of physical function as well as skeletal muscle mitchondrial function. Data were adjusted for age and gender using the Intent-To-Treat approach., Results: Adverse event frequency and type were similar between groups (n = 8 EX0, n = 12 EX500, and n = 7 EX1000). Overall, 85% of participants met the supplement adherence via pill counts while 82% met the exercise session adherence. Adjusted within group mean differences (95% confidence interval) from week 0 to 12 for gait speed ranged from -0.04 (EX0: -0.1, 0.03) m/s to 0.04 (EX1000: -0.02, 0.11) and the six-minute walk test mean differences were 9.45 (EX0: -9.02, 27.7), 22.9 (EX500: 4.18, 41.6), and 33.1 (EX1000: 13.8, 52.4) meters. Unadjusted mean differences for citrate synthase were -0.80 (EX0: -15.45, 13.84), -1.38 (EX500: -12.16, 9.39), and 7.75 (EX1000: -4.68, 20.18) mU/mg. COX activity mean within group changes ranged from -0.05 (EX0) to 0.06 (EX500) k/s/mg. Additional outcomes are detailed in the text., Conclusion: The pilot RCT indicated that combined EX + resveratrol was safe and feasible for older adults with functional limitations and may improve skeletal muscle mitochondrial function and mobility-related indices of physical function. A larger trial appears warranted and is needed to formally test these hypotheses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Older patients experience a decline in their physiologic reserves as well as chronic low-grade inflammation named "inflammaging." Both of these contribute significantly to aging-related factors that alter the acute, subacute, and chronic response of these patients to critical illness, such as sepsis. Unfortunately, this altered response to stressors can lead to chronic critical illness followed by dismal outcomes and death. The primary goal of this review is to briefly highlight age-specific changes in physiologic systems majorly affected in critical illness, especially because it pertains to sepsis and trauma, which can lead to chronic critical illness and describe implications in clinical management., Competing Interests: Disclosure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA 4977 ) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope ( 56 Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA 4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.

Aging is the primary risk factor for functional decline; thus, understanding and preventing disability among older adults has emerged as an important public health challenge of the 21st century. The science of gerontology - or geroscience - has the practical purpose of "adding life to the years." The overall goal of geroscience is to increase healthspan, which refers to extending the portion of the lifespan in which the individual experiences enjoyment, satisfaction, and wellness. An important facet of this goal is preserving mobility, defined as the ability to move independently. Despite this clear purpose, this has proven to be a challenging endeavor as mobility and function in later life are influenced by a complex interaction of factors across multiple domains. Moreover, findings over the past decade have highlighted the complexity of walking and how targeting multiple systems, including the brain and sensory organs, as well as the environment in which a person lives, can have a dramatic effect on an older person's mobility and function. For these reasons, behavioral interventions that incorporate complex walking tasks and other activities of daily living appear to be especially helpful for improving mobility function. Other pharmaceutical interventions, such as oxytocin, and complementary and alternative interventions, such as massage therapy, may enhance physical function both through direct effects on biological mechanisms related to mobility, as well as indirectly through modulation of cognitive and socioemotional processes. Thus, the purpose of the present review is to describe evolving interventional approaches to enhance mobility and maintain healthspan in the growing population of older adults in the United States and countries throughout the world. Such interventions are likely to be greatly assisted by technological advances and the widespread adoption of virtual communications during and after the COVID-19 era., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: Sepsis has been called a "disease of the elderly," and as in-hospital mortality has decreased, more sepsis survivors are progressing into poorly characterized long-term outcomes. The purpose of this study was to describe the current epidemiology of sepsis in older adults compared with middle-aged and young adults., Design: Prospective longitudinal study with young (≤45 years), middle-aged (46-64 years), and older (≥65 years) patient groups., Setting: University tertiary medical center., Participants: A total of 328 adult surgical intensive care unit (ICU) sepsis patients., Measurements: Patients were characterized by (1) baseline demographics and predisposition, (2) septic event, (3) hospital outcomes and discharge disposition, (4) 12-month mortality, and (5) Zubrod Performance Status, physical function (Short Physical Performance Battery and handgrip strength), and cognitive function (Hopkins Verbal Learning Test, Controlled Oral Word Association, and Mini-Mental Status Examination) at 3-, 6-, and 12-month follow-up. Loss to follow-up was due to death (in 68), consent withdrawal (in 32), and illness and scheduling difficulties: month 3 (in 51), month 6 (in 29), and month 12 (in 20)., Results: Compared with young and middle-aged patients, older patients had (1) significantly more comorbidities at presentation (eg, chronic renal disease 6% vs 12% vs 21%), intra-abdominal infections (14% vs 25% vs 37%), septic shock (12% vs 25% vs 36%), and organ dysfunctions; (2) higher 30-day mortality (6% vs 4% vs 17%) and fewer ICU-free days (median = 25 vs 23 vs 20); (3) more progression into chronic critical illness (22% vs 34% vs 42%) with higher poor disposition discharge to non-home destinations (19% vs 40% vs 62%); (4) worse 12-month mortality (11% vs 14% vs 33%); and (5) poorer Zubrod Performance Status and objectively measured physical and cognitive functions with only slight improvement over 12-month follow-up., Conclusion: Compared with younger patients, older sepsis survivors suffer both a higher persistent disability burden and 12-month mortality., (© 2020 The American Geriatrics Society.)

Previous studies have found an inverse relation between serum concentrations of interleukin (IL)-6 and physical performance in seniors, however this was limited to higher functioning older adults with low to moderate levels of inflammation. We explored the consistency of this association in a cohort of mobility limited older adults with chronic low-grade inflammation. This study included 289 participants (≥ 70 years old) with IL-6 level between 2.5 and 30 pg/mL and a walking speed < 1.0 m/sec from the ENRGISE Pilot study. Physical performance was assessed using the short physical performance battery (SPPB), usual gait speed over 400 m, grip strength, and knee extensor and flexor strength measured by isokinetic dynamometry at 60 and 180°/sec. There was a significant inverse correlation between log IL-6 and knee extensor strength at 60°/sec (r= -0.20, p = 0.002), at 180°/sec (r = -0.14, p = 0.037), and knee flexor strength at 60°/sec (r = -0.15, p = 0.021). After adjustment for potential confounders, the values of knee extensor strength at 60°/sec showed a trend toward a progressive reduction across IL-6 tertiles as IL-6 levels increased (p = 0.024). No significant association was found between IL-6 and other objectively measured physical performance. The findings were generally of smaller magnitude and less consistent than previously reported, which suggests that the associations are attenuated in those with both elevated inflammation and mobility limitations. These results have implications for planning and interpreting future intervention studies in older adults with low-grade inflammation and mobility limitations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Maintaining physical mobility is important for preventing age-related comorbidities in older adults. Endurance and resistance training prevent mobility loss in aging, but exercise alone does not always achieve the expected improvements in physical and cardiopulmonary function. Recent preclinical evidence suggests that a reason for the variability in exercise training responses may be the age-related dysregulation of the nicotinamide adenine dinucleotide (NAD+) metabolome. NAD+ is an essential enzymatic cofactor in energetic and signaling pathways. Endogenous NAD+ pool is lower in several chronic and degenerative diseases (e.g., cardiovascular diseases, Alzheimer's and Parkinson's diseases, muscular dystrophies), and also in aging. Exercise requires a higher energy expenditure than a resting state, thus a state of NAD+ insufficiency with reduced energy metabolism, could result in an inadequate exercise response. Recently, the NAD+ precursor nicotinamide riboside (NR), a vitamin B3 derivate, showed an ability to improve NAD+ metabolome homeostasis, restoring energy metabolism and cellular function in various organs in animals. NR has also been tested in older humans and is considered safe, but the effects of NR supplementation alone on physical performance are unclear. The purpose of this review is to examine the preclinical and clinical evidence on the effect of NR supplementation strategies alone and in combination with physical activity on mobility and skeletal muscle and cardiovascular function., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Context: Eating habits and food craving are strongly correlated with weight status. It is currently not well understood how psychological and behavioral factors influence both weight loss and weight regain., Objective: To examine the associations between psychological and behavioral predictors with weight changes and energy intake in a randomized controlled trial on weight loss., Design and Setting: The Prevention of Obesity Using Novel Dietary Strategies is a dietary intervention trial that examined the efficacy of 4 diets on weight loss over 2 years. Participants were 811 overweight (body mass index, 25-40.9 kg/m2; age, 30-70 years) otherwise healthy adults., Results: Every 1-point increase in craving score for high-fat foods at baseline was associated with greater weight loss (-1.62 kg, P = .0004) and a decrease in energy intake (r = -0.10, P = .01) and fat intake (r = -0.16, P < .0001) during the weight loss period. In contrast, craving for carbohydrates/starches was associated with both less weight loss (P < .0001) and more weight regain (P = .04). Greater cognitive restraint of eating at baseline was associated with both less weight loss (0.23 kg, P < .0001) and more weight regain (0.14 kg, P = .0027), whereas greater disinhibition of eating was only associated with more weight regain (0.12 kg, P = .01)., Conclusions: Craving for high-fat foods is predictive of greater weight loss, whereas craving for carbohydrates is predictive of less weight loss. Cognitive restraint is predictive of less weight loss and more weight regain. Interventions targeting different psychological and behavioral factors can lead to greater success in weight loss., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults., Methods: We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE-Pilot Study, and the LIFE Study., Results: The planning phase and the LIFE-Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69-0.98; P = .03), and that the intervention was cost-effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer-reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://agingresearchbiobank.nia.nih.gov)., Conclusions: The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872-881, 2020., (© 2020 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

Older adults are at high risk of developing cardiovascular disease (CVD). Pre-clinical studies indicate that resveratrol (RSV), a polyphenol commonly found in grapes and red wine, may help prevent development of CVD. Based on our previous reports where the 300 mg and 1000 mg doses appeared safe and improved psychomotor function in a dose-dependent manner, our hypothesis was that RSV would reduce biomarkers of CVD risk in overweight, but otherwise healthy older adults and that 1000 mg would lower CVD biomarkers >300 mg. This analysis was performed on samples from older participants (65 years and older) who were randomized to a 90 day RSV treatment with 300 mg (n = 10), 1000 mg (n = 9) or placebo (n = 10). We measured levels of CVD risk biomarkers i.e. oxidized low-density lipoprotein (oxLDL), soluble E-selectin-1 (sE-selectin), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), total plasminogen activator inhibitor (tPAI-1). Statistical significance was set at p < 0.05. Both sVCAM-1 and tPAI increased significantly more in the 1000 mg vs. 300 mg and placebo groups. Other biomarkers (300 mg vs. 1000 mg vs. placebo: oxLDL, sEselectin-1 and sICAM-1) followed the same trend toward higher levels in the 1000 mg group compared to the 300 mg and placebo groups, without reaching statistical significance. This pilot project suggests that a higher dose of RSV may increase the levels of CVD risk biomarkers in overweight older adults. Given no change in the CVD risk biomarkers in response to a lower dose, future studies should test the effects of different doses of RSV to evaluate potential detrimental effects of higher doses on CVD biomarkers and measures of cardiovascular function in older adults at risk for CVD., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)