Search

Alisa J Johnson,1,2,&ast; Taylor Buchanan,3,&ast; Chavier Laffitte Nodarse,1,2 Pedro A Valdes Hernandez,1,2 Zhiguang Huo,4 James H Cole,5,6 Thomas W Buford,3 Roger B Fillingim,1,2,7 Yenisel Cruz-Almeida1,2,7 1Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA; 2Department of Community Dentistry & Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL, USA; 3Department of Medicine, University of Alabama, Birmingham, AL, USA; 4Department of Biostatistics, College of Public Health & Health Professions College of Medicine, University of Florida, Gainesville, FL, USA; 5Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK; 6Dementia Research Centre, Institute of Neurology, University College London, London, UK; 7Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA&ast;These authors contributed equally to this workCorrespondence: Yenisel Cruz-Almeida, University of Florida, PO Box 103628, 1329 SW 16th Street, Ste 5180, Gainesville, FL, 32608, USA, Tel +1 352-294-8584, Fax +1 352-273-5985, Email cryeni@ufl.eduPurpose: Knee OA-related pain varies in impact across individuals and may relate to central nervous system alterations like accelerated brain aging processes. We previously reported that older adults with chronic musculoskeletal pain had a significantly greater brain-predicted age, compared to pain-free controls, indicating an “older” appearing brain. Yet this association is not well understood. This cross-sectional study examines brain-predicted age differences associated with chronic knee osteoarthritis pain, in a larger, more demographically diverse sample with consideration for pain’s impact.Patients and Methods: Participants (mean age = 57.8 ± 8.0 years) with/without knee OA-related pain were classified according to pain’s impact on daily function (ie, impact): low-impact (n=111), and high-impact (n=60) pain, and pain-free controls (n=31). Participants completed demographic, pain, and psychosocial assessments, and T1-weighted magnetic resonance imaging. Brain-predicted age difference (brain-PAD) was compared across groups using analysis of covariance. Partial correlations examined associations of brain-PAD with pain and psychosocial variables.Results: Individuals with high-impact chronic knee pain had significantly “older” brains for their age compared to individuals with low-impact knee pain (p < 0.05). Brain-PAD was also significantly associated with clinical pain, negative affect, passive coping, and pain catastrophizing (p’s< 0.05).Conclusion: Our findings suggest that high impact chronic knee pain is associated with an older appearing brain on MRI. Future studies are needed to determine the impact of pain-related interference and pain management on somatosensory processing and brain aging biomarkers for high-risk populations and effective intervention strategies.Keywords: knee osteoarthritis, high impact chronic pain, brain aging, experimental pain, psychosocial

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

Katie A Butera,1 Shannon R Roff,2 Thomas W Buford,3 Yenisel Cruz-Almeida4 1Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32610, USA; 2Charles River Laboratories Inc., Frederick, MD 21701, USA; 3Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; 4Department of Aging & Geriatric Research, Institute on Aging, Pain Research & Intervention Center of Excellence, Center for Cognitive Aging & Memory, University of Florida, Gainesville, FL 32610, USA Abstract: Multisite pain, or pain that occurs simultaneously at >1 anatomical site, is more prevalent than single-site pain. While multisite pain affects over half of older adults, it remains an understudied pain entity that may have important functional implications in an aging population. Greater understanding of this complex pain entity from a biopsychosocial perspective is critical for optimizing clinical and functional outcomes in older adults with pain. Therefore, the primary purpose of this review is to summarize the relationship between multisite pain and functional outcomes in older adults to further elucidate the impact of multisite pain as a distinct entity within this population. A comprehensive literature search revealed 17 peer-reviewed articles. Multisite pain in older individuals is associated with reductions in several physical function domains: 1) lower-extremity mobility; 2) upper-extremity impairments; 3) balance and increased fall risk; and 4) general disability and poor physical function. Further, multisite pain in older individuals is associated with psychological dysfunction (eg, anxiety and depressive symptoms) and social factors (eg, income and education). Overall, this review highlights the scant literature investigating the functional implications of multisite pain in an aging population. Further, while multisite pain appears to have functional consequences, the neurobiological mechanisms contributing to this relationship are unknown. Thus, how this pain characteristic may contribute to the variability in pain-related functional outcomes among older adults is not clear. Future investigations are strongly warranted to advance the understanding of multisite pain and its broad impact on physical and psychosocial function in older adults. Keywords: multiple pain locations, multiple pain sites, social function, dysfunction, disability, physical function, social factors

Rodrigo Ramirez-Campillo,1–3 Daniela Diaz,4 Cristian Martinez-Salazar,5 Pablo Valdés-Badilla,6 Pedro Delgado-Floody,5 Guillermo Méndez-Rebolledo,7 Rodrigo Cañas-Jamet,8,9 Carlos Cristi-Montero,10 Antonio García-Hermoso,11 Carlos Celis-Morales,12 Jason Moran,13 Thomas W Buford,14 Leocadio Rodriguez-Mañas,15 Alicia M Alonso-Martinez,16 Mikel Izquierdo16 1Department of Physical Activity Sciences, 2Laboratory of Measurement and Assessment in Sports, Research Nucleus in Health, Physical Activity and Sports, Universidad de Los Lagos, Osorno, 3Unit of Integrative Physiology, Laboratory of Exercise Sciences, MEDS Clinic, Santiago, Chile; 4School of Occupational Therapy, Faculty of Health, Universidad Santo Tomás, Osorno, 5Department of Physical Education, Sport and Recreation, Universidad de La Frontera, 6Institute of Physical Activity and Health, Universidad Autónoma de Chile, Temuco, 7School of Kinesiology, Faculty of Health, University Santo Tomás, Talca, 8Laboratory of Physiology, Department of Biological Sciences, Faculty of Biological Sciences, Universidad Andres Bello, Viña del Mar, 9School of Kinesiology, Faculty of Medicine, Universidad Diego Portales, Santiago, 10IRyS Group, Physical Education School, Pontificia Universidad Católica de Valparaíso, Valparaíso, 11Laboratory of Physical Activity Sciences, Sport and Health, Faculty of Medical Sciences, Universidad de Santiago de Chile, USACH, Santiago, Chile; 12BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, 13Centre for Sports and Exercise Science, School of Biological Sciences, University of Essex, Colchester, UK; 14Department of Aging and Geriatric Research, Institute of Aging, University of Florida, College of Medicine, Gainesville, Florida, USA; 15Division of Geriatric Medicine, University Hospital of Getafe, Madrid, 16Department of Health Sciences, Public University of Navarre, Navarre, Spain Objective: This study aimed to compare the effects of two frequencies of high-speed resistance training (HSRT) on physical performance and quality of life of older women.Methods: A total of 24 older women participated in a 12-week HSRT program composed of either two or three sessions/week (equated for volume and intensity). Women were randomized into three arms: a control group (CG, n=8), a resistance training group performing two sessions/week (RT2, n=8), and a resistance training group performing three sessions/week (RT3, n=8). The training program for both experimental groups included exercises that required high-speed concentric muscle actions.Results: No baseline differences were observed among groups. Compared with the CG, both training groups showed similar small to moderate improvements (P

Objective: Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH., Methods: The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, non-hazardous, and hazardous drinking. Data collection included demographics, medical history (i.e., comorbidities, treated hypertension, eGFR), alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson's correlation and Poisson regression models to estimate fall prevalence ratios (PR), adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR)., Results: The study included 315 PWH, aged 52 ± 12 years, with 78% male participants. Thirty-three percent were classified as non-drinking, 50% non-hazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls (PR: 2.12, 95% CI: 1.11-4.03) and recurrent falls (PR: 3.54, 95% CI: 1.21-10.3) among hazardous drinking compared to non-hazardous drinking, even after adjusting for confounders. The PR for falls per daily intake in grams was not statistically significant., Conclusions: There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C, but not when accessing recall of alcohol consumption in grams., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Ageing is an escalating global health issue, with the World Health Organization (WHO) reporting that one in six individuals will be 60 years or older by the year 2030. Therefore, understanding the mechanisms of complex biological ageing processes and associated healthcare challenges has become increasingly important. Intrinsic capacity (IC), defined by WHO as the composite of all physical and mental capacities an individual possesses, can be used as a proxy for defining healthy ageing. IC has five key components: locomotion, cognition, psychological, sensory, and vitality capacity (VC). This review paper specifically focuses on exercise as an effective tool to preserve VC in ageing populations. The physiological domains of VC discussed include energy and metabolism, neuromuscular function, immune and stress response, mitochondrial function, and the methylation clock. Additionally, we highlight potential outcome measures for assessing each of these domains. This review also covers areas of focus for future research and possible interventions. We ultimately conclude that ageing is a complex, multifaceted process resulting in deficits across multiple VC components. However, regular exercise is capable of producing physiological adaptations that may be beneficial in the context of healthy ageing and improving or preserving the status of VC components., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Frailty is common among cardiac patients; however, frailty assessment data from patients with peripheral arterial disease (PAD) are limited. The purpose of this observational study was to identify the prevalence and factors related to frailty in addition to unique frailty marker groupings in a cohort of sedentary adults with PAD. We grouped three PAD-relevant frailty characteristics using Fried's frailty phenotype -1) exhaustion, (2) weakness, and (3) slowness-and observed the prevalence of pre-frailty (1-2 characteristics) and frailty (3 characteristics) in the PAD cohort. Of the 106 participants, 34.9% were robust/non-frail, 53.8% were pre-frail, and 2.8% were frail. Exhaustion (33.3%) was the most occurring characteristic followed by weakness (20.0%) and slowness (5.0%). The grouping of weakness + slowness (10.0%) was the most prevalent followed by exhaustion + weakness (8.3%) and exhaustion + slowness (5.0%). Among pre-frail participants, ankle brachial index was correlated with a reduction in gait speed., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Low food security is common among people with HIV (PWH) and is associated with poorer health outcomes. Frailty, an aging-related outcome that is increasingly prevalent among PWH, may be stimulated by low food security. We assessed associations between food security and frailty among PWH., Methods: The Impact of Physical Activity Routines and Dietary Intake on the Longitudinal Symptom Experience of People Living with HIV (PROSPER-HIV) study follows PWH to evaluate how diet and physical activity impact symptoms. We utilized food security and frailty data from PROSPER-HIV Year 1 visits (January 2019 to July 2022) to estimate associations. Food security was measured via the validated two-item Food Security Questionnaire and categorized as Food Secure, Low Food Security, or Very Low Food Security. Frailty was measured with the Fried frailty phenotype, and categorized as robust, prefrail, and frail. We used relative risk regression to estimate associations between food security and frailty status, adjusted for demographic characteristics., Results: Among 574 PWH, nearly one-quarter were women (22%), mean age was 52 years old, 8% were frail, and 46% prefrail. Low food security was reported among nearly one-third of PWH: 13% Low Food Security and 18% Very Low Food Security. Compared with being Food Secure, we found Low Food Security was associated with frailty [prevalence ratio: 4.06 (95% confidence interval (CI) 2.16-7.62] and Very Low Food Security was associated with both prefrailty [1.48 (1.23-1.78)] and frailty [5.61 (3.14-10.0)], as compared with robust status., Conclusion: Low food security was associated with increased frailty among PWH in this study, suggesting a potential intervention point to promote healthy aging., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community. NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

Abstract: People with HIV (PWH) are at an increased risk for cognitive impairment. Lifestyle factors can have protective effects on cognition; little work has examined diet and cognitive function in PWH. In this cross-sectional pilot study, 86 PWH (mean age 56 years) completed diet recalls and a neurocognitive assessment. Correlations were conducted between diet and cognitive function, adjusting for total calories, sex, and education (multiple comparison correction p values are reported). Diet quality of the sample was poor. Greater calories per day ( r = 0.28, p =.08) and greater percentage of calories from saturated fatty acids (SFAs; r = 0.26, p = 0.08) were associated with better cognition. Higher intake of SFAs ( r s 0.30-0.31, p s = 0.07), amino acids ( r s = 0.27, p s = 0.08), and phosphorus ( r = 0.29, p = .07) and magnesium ( r = 0.25, p = .08) were associated with better cognition. A diet reflecting higher protein and fat relative to carbohydrates was associated with better cognition. Targeting individual nutrients, improving diet quality, and adequate caloric intake may preserve cognition in PWH., (Copyright © 2024 Association of Nurses in AIDS Care.)

Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD., Methods: Forty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype., Results: Abnormal myofibre proportion was defined in males with COPD (n = 29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n = 17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density., Conclusions: Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear., Methods: Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I 2 statistic. All hypothesis testing was two-sided with an alpha of 0.05., Results: Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I 2  = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I 2  = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I 2  = 0.0%)., Conclusions: LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Alzheimer's disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV., Methods: This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone-binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function., Results: Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (β = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (β = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (β = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (β = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (β = -0.004, P = 0.01); no statistically significant associations were observed for handgrip., Conclusion: Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Delirium is a common complication during acute care hospitalizations in older adults. A substantial percentage of admissions are for ambulatory care-sensitive conditions (ACSCs) or potentially avoidable hospitalizations-conditions that might be treated early in the outpatient setting to prevent hospitalization and hospital complications., Methods: This retrospective cross-sectional study examined rates of delirium among older adults hospitalized for ACSCs. Participants were 39 933 older adults ≥65 years of age admitted from January 1, 2015 to December 31, 2019 to general inpatient units and ICUs of a large Southeastern academic medical center. Delirium was defined as a score ≥ 2 on the Nursing Delirium Screening Scale or positive on the Confusion Assessment Method for the Intensive Care Unit during admission, and ACSCs were identified from the primary admission diagnosis using standardized definitions. Generalized linear mixed models were used to examine the association between ACSCs and delirium, compared with admissions for non-ACSC diagnoses, adjusting for covariates and repeated observations for individuals with multiple admissions., Results: Delirium occurred in 15.6% of admissions for older adults. Rates were lower for ACSC admissions versus admissions for other conditions (13.9% vs 15.8%, p < .001). Older age and higher comorbidity were significant predictors of the development of delirium., Conclusions: Rates of delirium among older adults hospitalized for ACSCs were lower than rates for non-ACSC hospitalization but still substantial. Optimizing the treatment of ACSCs in the outpatient setting is an important goal not only for reducing hospitalizations but also for reducing risks for hospital-associated complications such as delirium., (© The Author(s) 2023. 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: Among individuals with heart failure (HF), racial differences in comorbidities may be mediated by social determinants of health (SDOH)., Methods: Black and White US community-dwelling participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study aged ≥ 45 years with an adjudicated HF hospitalization between 2003 and 2017 were included in this cross-sectional analysis. We assessed whether higher prevalence of comorbidities in Black participants compared to White participants were mediated by SDOH in socioeconomic, environment/housing, social support, and healthcare access domains, using the inverse odds weighting method., Results: Black (n = 240) compared to White (n = 293) participants with HF with preserved ejection fraction (HFpEF) had higher prevalence of diabetes [1.38 (95% CI: 1.18 - 1.61)], chronic kidney disease [1.21 (95% CI: 1.01 - 1.45)], and anemia [1.33 (95% CI: 1.02 - 1.75)] and lower prevalence of atrial fibrillation [0.80 (95% CI: (0.65 - 0.98)]. Black (n = 314) compared to White (n = 367) participants with HF with reduced ejection fraction (HFrEF) had higher prevalence of hypertension [1.04 (95% CI: 1.02 - 1.07)] and diabetes [1.26 (95% CI: 1.09 - 1.45)] and lower prevalence of coronary artery disease [0.86 (95% CI: 0.78 - 0.94)] and atrial fibrillation [0.70 (95% CI: 0.58 - 0.83)]. Socioeconomic status explained 14.5%, 26.5% and 40% of excess diabetes, anemia, and chronic kidney disease among Black adults with HFpEF; however; mediation was not statistically significant and no other SDOH substantially mediated differences in comorbidity prevalence., Conclusions: Socioeconomic status partially mediated excess diabetes, anemia, and chronic kidney disease experienced by Black adults with HFpEF, but differences in other comorbidities were not explained by other SDOH examined., Competing Interests: Dr. Emily B. Levitan receives funding from Amgen Inc.

Introduction: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident., Methods: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index., Results: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048)., Implications: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: People with HIV (PWH) are aging and are experiencing higher rates of abdominal adiposity. Physical activity is an effective nonpharmacological strategy to reduce adiposity in the general aging population. Yet, the relationship between physical activity and adiposity in people with well controlled HIV is unclear. Our objective was to describe the association between objectively-measured physical activity and abdominal adiposity in PWH., Methods: As part of the multisite, observational PROSPER-HIV study, virologically suppressed, adult PWH wore an Actigraph accelerometer for 7-10 days and completed duplicate waist and hip circumference measures. Demographic and medical characteristics were abstracted from the CFAR Network of Integrated Clinical Systems dataset. Descriptive statistics and multiple linear regressions were used to analyze the data., Results: On average, our 419 PWH were 58 years of age [interquartile range (IQR): 50, 64], male (77%), Black (54%), and currently taking an integrase inhibitor (78%). PWH completed a mean of 7.06 (±2.74) days of total actigraphy wear time. They took an average of 4905 (3233, 7140) steps per day and engaged in 5.4 h of sedentary time per day. Controlling for age, sex, employment and integrase inhibitor use, the number of steps taken per day was associated with reduced abdominal adiposity ( F  = 3.27; P  < 0.001) and the hours of daily sedentary time was associated with increased abdominal adiposity ( F  = 3.24; P  < 0.001)., Conclusions: Greater physical activity is associated with reduced abdominal adiposity in aging PWH. Future work should investigate how to tailor the amount, type and intensity of physical activity needed to reduce adiposity in PWH taking contemporary HIV medication., Registration Number: NCT03790501., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hospital-associated disability (HAD) is a common complication during the course of acute care hospitalizations in older adults. Many admissions are for ambulatory care sensitive conditions (ACSCs), considered potentially avoidable hospitalizations-conditions that might be treated in outpatient settings to prevent hospitalization and HAD. We compared the incidence of HAD between older adults hospitalized for ACSCs versus those hospitalized for other diagnoses., Methods: We conducted a retrospective cohort study in inpatient (non-ICU) medical and surgical units of a large southeastern regional academic medical center. Participants were 38,960 older adults ≥ 65 years of age admitted from January 1, 2015, to December 31, 2019. The primary outcome was HAD, defined as decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We used generalized linear mixed models to examine differences in HAD between hospitalizations with a primary diagnosis for an ACSC using standard definitions versus primary diagnosis for other conditions, adjusting for covariates and repeated observations for individuals with multiple hospitalizations., Results: We found that 10% of older adults were admitted for an ACSC, with rates of HAD in those admitted for ACSCs lower than those admitted for other conditions (16% vs. 20.7%, p < 0.001). Age, comorbidity, admission functional status, and admission cognitive impairment were significant predictors for development of HAD. ACSC admissions to medical and medical/surgical services had lower odds of HAD compared with admissions for other conditions, with no significant differences between ACSC and non-ACSC admissions to surgical services., Conclusions: Rates of HAD among older adults hospitalized for ACSCs are substantial, though lower than rates of HAD with hospitalization for other conditions, reflecting that acute care hospitalization is not a benign event in this population. Treatment of ACSCs in the outpatient setting could be an important component of efforts to reduce HAD., (© 2023 The American Geriatrics Society.)

Angiotensin (1-7) [Ang (1-7)] is an active heptapeptide of the noncanonical arm of the renin-angiotensin system that modulates molecular signaling pathways associated with vascular and cellular inflammation, vasoconstriction, and fibrosis. Preclinical evidence suggests that Ang (1-7) is a promising therapeutic target that may ameliorate physical and cognitive function in late life. However, treatment pharmacodynamics limits its clinical applicability. Therefore, this study explored the underlying mechanisms altered by a genetically modified probiotic (GMP) that expresses Ang (1-7) combined with and without exercise training in an aging male rat model as a potential adjunct strategy to exercise training to counteract the decline of physical and cognitive function. We evaluated cross-tissue (prefrontal cortex, hippocampus, colon, liver, and skeletal muscle) multi-omics responses. After 12 wk of intervention, the 16S mRNA microbiome analysis revealed a main effect of probiotic treatment within- and between groups. The probiotic treatment enhanced α diversity (Inverse Simpson ( F [2,56] = 4.44; P = 0.02); Shannon-Wiener ( F [2,56] = 4.27; P = 0.02)) and β-diversity ( F [2,56] = 2.66; P = 0.01) among rats receiving our GMP. The analysis of microbes' composition revealed three genera altered by our GMP ( Enterorhabdus , Muribaculaceae unclassified , and Faecalitalea ). The mRNA multi-tissue data analysis showed that our combined intervention upregulated neuroremodeling pathways on prefrontal cortex (i.e., 140 genes), inflammation gene expression in the liver (i.e., 63 genes), and circadian rhythm signaling on skeletal muscle. Finally, the integrative network analysis detected different communities of tightly (| r | > 0.8 and P < 0.05) correlated metabolites, genera , and genes in these tissues. NEW & NOTEWORTHY This manuscript uses a multiomics approach (i.e., microbiome, metabolomics, and transcriptomics) to explore the underlying mechanisms driven by a genetically modified probiotic (GMP) designed to express angiotensin (1-7) combined with moderate exercise training in an aged male rat model. After 12 wk of intervention, our findings suggest that our GMP enhanced gut microbial diversity while exercise training altered the transcriptional response in relevant neuroremodeling genes, inflammation, and circadian rhythm signaling pathways in an aging animal model.

Objective: To examine whether delirium predicts occurrence of hospital-associated disability (HAD), or functional decline after admission, among hospitalized older adults., Design: Retrospective cross-sectional study., Setting and Participants: General inpatient (non-ICU) units of a large regional Southeastern US academic medical center, involving 33,111 older adults ≥65 years of age admitted from January 1, 2015, to December 31, 2019., Methods: Delirium was defined as a score ≥2 on the Nursing Delirium Screening Scale (NuDESC) during hospital admission. HAD was defined as a decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. Generalized linear mixed models were used to examine the association between delirium and HAD, adjusting for covariates and repeated observations with multiple admissions. We performed multivariate and mediation analyses to examine strength and direction of association between delirium and HAD., Results: One-fifth (21.6%) of older adults developed HAD during hospitalization and experienced higher delirium rates compared to those not developing HAD (24.3% vs 14.3%, P < .001). Age, presence of delirium, Elixhauser Comorbidity Score, admission cognitive status, admission ADL function, and length of stay were associated (all P < .001) with incident HAD. Mediational analyses found 46.7% of the effect of dementia and 16.7% of the effect of comorbidity was due to delirium (P < .001)., Conclusions and Implications: Delirium significantly increased the likelihood of HAD within a multivariate predictor model that included comorbidity, demographics, and length of stay. For dementia and comorbidity, mediation analysis showed a significant portion of their effect attributable to delirium. Overall, these findings suggest that reducing delirium rates may diminish HAD rates., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Middle-aged and older people living with HIV (PWH) are at higher risk for cognitive impairment and engage in lower levels of physical activity (PA) than seronegative counterparts. Research examining the association between objectively-measured PA and cognitive function in this population is scarce. This cross-sectional study examined the association between accelerometry-measured PA and cognitive functioning among 75 PWH (mean age 55.63). Light PA was the PA variable with the most consistent associations with cognition, with more minutes per week of light PA (performed in bouts of ≥ 10 min) being associated with better executive function, working memory/attention, and speed of processing performance, adjusted for age and current CD4 count. Findings suggest that although middle-aged and older PWH engage in more light than moderate-to-vigorous PA, light PA may be beneficial to cognition. Longitudinal studies are needed to understand PA dose-response associations with cognitive trajectories, cognitive domain specificity of PA effects, and underlying neural mechanisms of PA., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Modifications to Fried's frailty phenotype (FFP) are common. We evaluated a self-reported modified frailty phenotype (Mod-FP) used among people with HIV (PWH). Among 522 PWH engaged in two longitudinal studies, we assessed validity of the four-item Mod-FP compared with the five-item FFP. We compared the phenotypes via receiver operator characteristic curves, agreement in classifying frailty, and criterion validity via association with having experienced falls. Mod-FP classified 8% of PWH as frail, whereas FFP classified 9%. The area under the receiver operator characteristic curve for Mod-FP classifying frailty was 0.93 (95% CI = 0.91-0.96). We observed kappa ranging from 0.64 (unweighted) to 0.75 (weighted) for categorizing frailty status. Both definitions found frailty associated with a greater odds of experiencing a fall; FFP estimated a slightly greater magnitude (i.e., OR) for the association than Mod-FP. The Mod-FP has good performance in measuring frailty among PWH and is reasonable to use when the gold standards of observed assessments (i.e., weakness and slowness) are not feasible., (Copyright © 2023 Association of Nurses in AIDS Care.)

Abstract: The role of cardiometabolic diseases (CMDs) on physical health-related quality of life (P-HRQoL) and quality of sleep was examined among 261 PLWH ≥40 years, recruited from a university-affiliated HIV clinic in the Deep U.S. South. Using a cross-sectional study design, participants completed the Medical Outcomes Study HIV Health Survey (MOS-HIV; P-HRQoL) and Pittsburgh Sleep Quality Index. The overall prevalence of self-reporting ≥1 CMD was 64.4%. P-HRQoL scores were lower in PLWH with ≥1 CMD compared with those with no CMDs (45.53 ± 11.54 vs. 49.67 ± 10.77, p <.01). Poor sleep quality was higher among participants with ≥1 CMD compared with those with no CMDs (9.28 ± 4.42 vs. 7.26 ± 4.17, p <.01). Each additional CMD resulted in a 1.83-point decrease in P-HRQoL and 0.74-point increase in poor sleep quality scores. Interventions that focus on targeting these quality-of-life domains in PLWH with CMDs are needed., (Copyright © 2022 Association of Nurses in AIDS Care.)

Age-related declines in physical and cognitive function can have tremendous, negative impacts on health span and quality of life. Therefore, we investigated the potential of utilizing a probiotic treatment to target the renin-angiotensin system (RAS) in conjunction with moderate exercise to ameliorate age-related declines in cognitive and physical function in aged rats. Herein we utilized a genetically modified angiotensin (1-7), which activates a "complementary" arm of the RAS through binding Mas (AT7) receptors. This process induces several beneficial physiologic effects, including decreased inflammation and enhanced physical/cognitive function. Thus, in this short research report, we suggest the efficacy of this Ang(1-7) releasing Lactobacillus paracasei (LPA) as either an alternative strategy to exercise, or more likely as an adjuvant to moderate exercise, for the prevention of both physical and cognitive decline especially in female rats., (© The Author(s) 2022. 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.)

Exercise is a cornerstone of preventive medicine and a promising strategy to intervene on the biology of aging. Variation in the response to exercise is a widely accepted concept that dates back to the 1980s with classic genetic studies identifying sequence variations as modifiers of the VO 2 max response to training. Since that time, the literature of exercise response variance has been populated with retrospective analyses of existing datasets that are limited by a lack of statistical power from technical error of the measurements and small sample sizes, as well as diffuse outcomes, very few of which have included older adults. Prospective studies that are appropriately designed to interrogate exercise response variation in key outcomes identified a priori and inclusive of individuals over the age of 70 are long overdue. Understanding the underlying intrinsic (e.g., genetics and epigenetics) and extrinsic (e.g., medication use, diet, chronic disease) factors that determine robust versus poor responses to various exercise factors will be used to improve exercise prescription to target the pillars of aging and optimize the clinical efficacy of exercise training in older adults. This review summarizes the proceedings of the NIA-sponsored workshop entitled, "Understanding Heterogeneity of Responses to, and Optimizing Clinical Efficacy of, Exercise Training in Older Adults" and highlights the importance and current state of exercise response variation research, particularly in older adults, prevailing challenges, and future directions., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Endurance exercise alters the gut microbiome independently of diet. The extent to which gut microbes are responsible for physiologic adaptations to exercise training is unknown. The purpose of these experiments was to determine the role of gut microbes in performance and muscle adaptation to 6 wk of voluntary wheel running (VWR) in mice., Methods: We depleted microbes with broad-spectrum antibiotic (ABX) treatment and used germ-free (GF) mice to determine effects on adaptations to VWR. Male and female C57Bl/6 mice ( n = 56) were assigned to daily VWR or sedentary conditions. After the intervention, treadmill endurance and glucose tolerance were assessed, and gastrocnemius and soleus tissues were harvested and analyzed for citrate synthase (CS) enzyme activity and expression of exercise training-sensitive genes., Results: ABX treatment and GF status resulted in VWR volumes ~22% and 26% lower than controls, respectively. Analysis of variance revealed that, although VWR increased treadmill endurance, ABX had no effect. GF status significantly reduced treadmill performance in trained GF mice after training. VWR increased gastrocnemius CS enzyme activity in all groups, and ABX and GF status did not reduce the VWR effect. VWR also increased muscle expression of PGC1a, but this was not affected by ABX treatment., Conclusions: ABX treatment and GF status reduced VWR behavior but did not affect VWR-induced adaptations in endurance capacity, CS activity, or expression of muscle metabolic genes. However, GF status reduced endurance capacity. These data indicated that reducing microbes in adulthood does not inhibit endurance training adaptations in C57Bl/6 mice, but that GF mice possess a reduced responsiveness to endurance exercise training, perhaps because of a developmental defect associated with lack of microbes from birth., (Copyright © 2022 by the American College of Sports Medicine.)

Background: Inflammation is an indicator of oxidative stress that may contribute to cardiovascular diseases in older people living with HIV (OPWH). Physical activity (PA) may reduce these biomarkers in OPWH, but little is known about the association of PA with inflammatory and cardiovascular biomarkers. We sought to examine the inflammatory and cardiovascular biomarker correlates of PA and sedentary behavior in OPWH., Methods: We included 101 OPWH with complete assessments of PA, sedentary behavior, and biomarker data to examine the association between the volume of PA and inflammatory and cardiovascular biomarkers., Results: In this cohort of OPWH (mean age 55.9 y), 68% were male and 83% were African American/Black. Among OPWH, greater volume of PA (ie, walking, moderate, vigorous, and/or total) was associated with lower systolic (P < .05) and diastolic blood pressure (P < .05), pulse pressure (P < .05), and tumor necrosis factor-alpha (P < .05). Greater duration of sitting was associated with greater triglycerides, interleukin-6, and tumor necrosis factor-alpha (P < .05)., Conclusions: Although adherence to regular PA among OPWH is low and sedentary behavior is high, the associations between biomarkers and PA suggest a greater volume of PA could attenuate the inflammatory and cardiovascular derangements experienced by OPWH.

Background: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines., Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models., Results: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults., Conclusions: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.

Declining health, gut dysbiosis, and cognitive impairments are hallmarks of advanced age. While caloric restriction is known to robustly extend the healthspan and alter gut microbiome composition, it is difficult maintain. Time-restricted feeding or changes in dietary macronutrient composition could be feasible alternatives for enhancing late life cognitive and physical health that are easier to comply with for extended periods of time. To investigate this possibility, 8-month-old rats were placed on time-restricted feeding with a ketogenic or micronutrient- and calorically matched control diet for 13 months. A third group of rats was permitted to eat standard chow ad libitum during this time. At 22 months, all rats were tested on a biconditional association task and fecal samples were collected for microbiome composition analysis. Regardless of dietary composition, time-restricted-fed rats had better cognitive performance than ad libitum-fed rats. This observation could not be accounted for by differences in motivation, procedural or sensorimotor impairments. Additionally, there were significant differences in gut microbiome diversity and composition between all diet conditions. Allobaculum abundance was associated with cognitive task performance, indicating a link between gut health and cognitive outcomes in aged subjects. Overall, time restricted feeding had the largest influence on cognitive performance in aged rats., Competing Interests: The authors declare no conflict of interest.

Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as "the Deep South", is an economically and culturally unique region ravaged by pervasive health disparities - thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region., (© 2022. The Author(s).)

Introduction: Neutrophil to Lymphocyte Ratio (NLR) combines a marker of inflammation and reduced cell turnover to reflect age related alterations in the immune system. Whether NLR can serve as a biomarker of frailty and predict survival among older adults with Multiple Myeloma (MM) is unknown., Materials and Methods: We used an electronic health record-derived database to identify older adults (age ≥ 60y) with incident MM diagnosed between 1/2011 and 2/2020, with known pre-treatment absolute neutrophil and lymphocyte count up to 90 days before the start of therapy. The calculated NLR values were stratified into quartiles (Q1-Q4). We constructed a previously validated, simplified frailty index combining age, comorbidity and ECOG performance status. We measured the association between NLR quartiles and this frailty index using a logistic regression, adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for potential confounders., Results: We identified 1729 older adults with newly diagnosed MM, at a median age of 73y (IQR: 67-78y). The median NLR was 2.13 (IQR: 1.44 to 3.31). Of the 1135 evaluable patients, 55% met criteria for frailty. Multivariable analysis revealed a 2.1-fold higher odds of frailty (95%CI = 1.42-3.10, p < 0.001) for patients in the NLR Q4 group vs. NLR Q1 group. In a multivariable analysis, adjusting for age, sex, race/ethnicity, M-protein type, stage, high risk cytogenetics, baseline creatinine, LDH and type of first line therapy, patients in NLR Q4 group had a 1.51 times increased hazards of death (95%CI = 1.15-1.98, p 0.002) when compared to those in NLR Q1 group., Conclusion: NLR, a readily available laboratory biomarker, is associated with frailty measured using a simplified frailty index as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM., Competing Interests: Declaration of Competing Interest SG reports receiving research funding from Carevive and PackHealth, and honorarium from Carevive and Sanofi. AJO reports research funding from Genentech, TG Therapeutics, Spectrum Pharmaceuticals, Celldex Pharmaceuticals, and Adaptive Biotechnologies. SB has received research funding from Amyloid Foundation. KG does not have any relevant disclosures. LJC receives honoraria from Amgen, Bristol-Myers Squibb, AbbVie, and Janssen, and grant/research support from Amgen, Bristol-Myers Squibb, AbbVie, and Janssen., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Both ketogenic diets (KD) and time-restricted feeding (TRF) regimens have the ability to influence several parameters of physical health, including gut microbiome composition and circulating cytokine concentration. Moreover, both of these dietary interventions prevent common impairments associated with the aging process. However, significantly altering macronutrient intake, which is required for a KD, may be unappealing to individuals and decrease compliance to dietary treatments. In contrast to a KD, TRF allows individuals to continue eating the foods they are used to, and only requires a change in the time of day at which they eat. Therefore, we investigated both a KD and a diet with a more Western-like macronutrient profile in the context of TRF, and compared both diets to animals allowed access to standard chow ad libitum in young adult and aged rats. While limited effects on cytokine levels were observed, both methods of microbiome analysis (16S sequencing and metagenomics) indicate that TRF and KDs significantly altered the gut microbiome in aged rats. These changes were largely dependent on changes to feeding paradigm (TRF vs. ad libitum) alone regardless of macronutrient content for many gut microbiota, but there were also macronutrient-specific changes. Specifically, functional analysis indicates significant differences in several pathways, including those involved in the tricarboxylic acid (TCA) cycle, carbohydrate metabolism and neurodegenerative disease. These data indicate that age- and disease-related gut dysbiosis may be ameliorated through the use of TRF with both standard diets and KDs.

For centuries, regular exercise has been acknowledged as a potent stimulus to promote, maintain, and restore healthy functioning of nearly every physiological system of the human body. With advancing understanding of the complexity of human physiology, continually evolving methodological possibilities, and an increasingly dire public health situation, the study of exercise as a preventative or therapeutic treatment has never been more interdisciplinary, or more impactful. During the early stages of the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC) Initiative, the field is well-positioned to build substantially upon the existing understanding of the mechanisms underlying benefits associated with exercise. Thus, we present a comprehensive body of the knowledge detailing the current literature basis surrounding the molecular adaptations to exercise in humans to provide a view of the state of the field at this critical juncture, as well as a resource for scientists bringing external expertise to the field of exercise physiology. In reviewing current literature related to molecular and cellular processes underlying exercise-induced benefits and adaptations, we also draw attention to existing knowledge gaps warranting continued research effort. © 2021 American Physiological Society. Compr Physiol 12:3193-3279, 2022., (Copyright © 2022 American Physiological Society. All rights reserved.)

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Chronic low back pain (cLBP) is the most common reason for individual suffering and health care utilization in adults. Ample evidence suggests sociodemographic variables and socioeconomic status (SES) influence pain. However, a framework informing associations on race, SES, and the utilization of pharmacologic therapies and provider type are limited-particularly in cLBP. Thus, this study examined the extent to which sociodemographic (i.e., age, race, and gender) and socioeconomic factors (i.e., national area deprivation index, NADI) influence pain treatment (i.e., NSAIDs, opioids, antidepressants, and non-NSAIDs) and provider utilization for cLBP (i.e., no provider care, primary care, or tertiary care). Eligible participants with cLBP completed a series of questionnaires. Of the 174 participants, 58% were women, 59% were non-Hispanic Black (NHB), and the mean age was 46.10 (SD 13.58). Based on NADI distributions by race, NHB participants lived in more socioeconomically disadvantaged neighborhoods ( p < 0.001) than non-Hispanic White (NHW) adults. Results suggested that the use of one or more pharmacologic therapies was associated with race ( p = 0.021). Specifically, NHW adults were two times more likely to take one or more pharmacologic therapies than NHBs ( p = 0.009). NHWs were also more likely to use NSAIDs ( p = 0.041) and antidepressants ( p < 0.001) than NHBs. Furthermore, provider utilization was significantly associated with gender ( p = 0.037) and age ( p = 0.018); which suggests older women were more likely to use primary or tertiary care. Findings from this study expand on the existing literature as it relates to associations between disparities in access to healthcare providers and access to medications. Future research should seek to understand differences in age and utilization of primary or tertiary care providers and continue to examine the influence of sociodemographic and SES factors to cLBP and compare with other types of chronic pain., 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 © 2022 Allen-Watts, Sims, Buchanan, DeJesus, Quinn, Buford, Goodin and Rumble.)

While neurodegenerative diseases can strike at any age, the majority of afflicted individuals are diagnosed at older ages. Due to the important impact of age in disease diagnosis, the field of neuroscience could greatly benefit from the many of the theories and ideas from the biology of aging-now commonly referred as geroscience. As discussed in our complementary perspective on the topic, there is often a "silo-ing" between geroscientists who work on understanding the mechanisms underlying aging and neuroscientists who are studying neurodegenerative diseases. While there have been some strong collaborations between the biology of aging and neuroscientists, there is still great potential for enhanced collaborative effort between the 2 fields. To this end, here, we review the state of the geroscience field, discuss how neuroscience could benefit from thinking from a geroscience perspective, and close with a brief discussion on some of the "missing links" between geroscience and neuroscience and how to remedy them. Notably, we have a corresponding, concurrent review from the neuroscience perspective. Our overall goal is to "bridge the gap" between geroscience and neuroscience such that more efficient, reproducible research with translational potential can be conducted., (© 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.)

Neuroscience has a rich history of studies focusing on neurobiology of aging. However, much of the aging studies in neuroscience occur outside of the gerosciences. The goal of this primer is 2-fold: first, to briefly highlight some of the history of aging neurobiology and second, to introduce to geroscientists the broad spectrum of methodological approaches neuroscientists use to study the neurobiology of aging. This primer is accompanied by a corresponding geroscience primer, as well as a perspective on the current challenges and triumphs of the current divide across these 2 fields. This series of manuscripts is intended to foster enhanced collaborations between neuroscientists and geroscientists with the intent of strengthening the field of cognitive aging through inclusion of parameters from both areas of expertise., (© 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: While extensive research on the brain has failed to identify effective therapies, using probiotics to target the gut microbiome has shown therapeutic potential in Alzheimer's disease (AD). Genetically modified probiotics (GMP) are a promising strategy to deliver key therapeutic peptides with high efficacy and tissue specificity. Angiotensin (Ang)-(1-7) levels inversely correlate to AD severity, but its administration is challenging. Our group has successfully established a GMP-based method of Ang-(1-7) delivery., Objective: Since Drosophila represents an excellent model to study the effect of probiotics on complex disorders in a high throughput manner, we tested whether oral supplementation with Lactobacillus paracasei releasing Ang-(1-7) (LP-A) delays memory loss in a Drosophila AD model., Methods: Flies overexpressing the human amyloid-β protein precursor and its β-site cleaving enzyme in neurons were randomized to receive four 24-h doses of Lactobacillus paracasei alone (LP), LP-A or sucrose over 14 days. Memory was assessed via an aversive phototaxic suppression assay., Results: Optimal dilution,1:2, was determined based on palatability. LP-A improved memory in trained AD males but worsened cognition in AD females. LP-supplementation experiments confirmed that Ang-(1-7) conferred additional cognitive benefits in males and was responsible for the deleterious cognitive effects in females. Sex-specific differences in the levels of angiotensin peptides and differential activation of the kynurenine pathway of tryptophan metabolism in response to supplementation may underlie this male-only therapeutic response., Conclusion: In summary, LP-A ameliorated the memory deficits of a Drosophila AD model, but effects were sex-specific. Dosage optimization may be required to address this differential response.

Purpose: Fatigue is a component of frailty and may undermine functional well-being and independent living. The prevalence of fatigue and its impact on functional limitations among older adults with cancer remains understudied., Methods: Using participants enrolled in the Cancer and Aging Resilience Evaluation (CARE), a prospective registry of patients (≥ 60 years) with cancer, who underwent a geriatric assessment (GA) at the first visit with oncology, we examined the presence of fatigue based on self-report of moderate to severe fatigue on PROMIS global health 10-item instrument at the time of GA. We examined the association of fatigue with impairments in instrumental activities of daily living (IADL) and activities of daily living (ADL) adjusting for age, sex, race/ethnicity, education, cancer type and stage, pain, comorbidities, and time from cancer., Results: We included 374 older adults with cancer with a median age of 70 years; 56% were male and 23% black. Diagnoses included colorectal (33%) and pancreatic cancers (25%), with most patients with advanced stage disease (71% stage III/IV). Overall, 210 (58%) patients reported significant fatigue. Patients reporting significant fatigue had an increased odds of IADL (adjusted odds ratio, aOR 1.9; 95% CI 1.1-3.2) or ADL impairment (aOR 3.6; 95% CI 1.4-9.3), as compared to those without, after adjusting for aforementioned confounders., Conclusions: Over half of older adults with cancer reported moderate to severe fatigue that was independently associated with functional status limitations. Further understanding of the multifaceted aspects of fatigue and development of interventions combating fatigue in this population is urgently needed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Growing research suggests that aerobic high-intensity interval training (HIIT) improves cardiovascular function and physical performance compared with moderate intensity continuous training (MICT). However relatively few animal models of HIIT are available to inform about the benefits of this exercise-particularly among older animals. In addition, there is little evidence for how HIIT training interacts with adjuvant pharmacological therapies known to enhance the impact of MCIT in older individuals such as Angiotensin Converting Enzyme (ACE) Inhibitors., Purpose: The aim of the present study was to establish a HIIT protocol in aged rats based on forced running wheel-bed, and to subsequently (1) establish the feasibility of the HIIT protocol in a proof-of-concept study evaluating interactions between HIIT and (2) the result of combining HIIT + ACE inhibitor treatment using the ACE inhibitor enalapril., Methods: Two groups of rats were used in this study. The feasibility of using wheel-bed for HIIT training was tested in group one (15- and 30-month-old male rats). In the second group, 37 24-month-old Fisher 344 × Brown Norway male rats were randomly divided into four subgroups: control, enalapril, HIIT training group, and HIIT training combined with enalapril administration. The training and administration lasted for 4 weeks. After the intervention, locomotor activity, exercise tolerance, and grip strength were tested., Results: Our feasibility study suggested that middle-aged and aged rats were able to successfully complete the HIIT training. In our intervention study, HIIT training alone, regardless of adjuvant enalapril intervention, did raise treadmill exercise tolerance vs. the sedentary condition. Measures of healthspan were not negatively impacted by HIIT training., Conclusion: The novel HIIT protocol based on forced running wheel-bed was successfully employed in aged rats. We conclude that future studies should compare the results and of multi-modal intervention strategies which include both HIIT and MICT in combination with adjuvant therapies such as enalapril to improve exercise tolerance and other global indices of healthspan., Competing Interests: Conflict of Interest: 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.

The UAB Nathan Shock Center focuses on comparative energetics and aging. Energetics, as defined for this purpose, encompasses the causes, mechanisms, and consequences of the acquisition, storage, and use of metabolizable energy. Comparative energetics is the study of metabolic processes at multiple scales and across multiple species as it relates to health and aging. The link between energetics and aging is increasingly understood in terms of dysregulated mitochondrial function, altered metabolic signaling, and aberrant nutrient responsiveness with increasing age. The center offers world-class expertise in comprehensive, integrated energetic assessment and analysis from the level of the organelle to the organism and across species from the size of worms to rats as well as state-of-the-art data analytics. The range of services offered by our three research cores, (1) The Organismal Energetics Core, (2) Mitometabolism Core, and (3) Data Analytics Core, is described herein., (© 2021. American Aging Association.)