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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.

Abstract 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 VO2max 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.

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 P P P 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.

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.

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

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 six weeks of voluntary wheel running (VWR) in mice.We depleted microbes with broad-spectrum antibiotic treatment (ABX) 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.ABX treatment and GF status resulted in VWR volumes ~22% and 26% lower than controls, respectively. Analysis of variance revealed that while VWR increased treadmill endurance, ABX had no effect. GF status significantly reduced treadmill performance in trained GF mice post-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.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 due to a developmental defect associated with lack of microbes from birth.

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.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.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.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.

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.

Introduction: Heart failure (HF) is often accompanied by comorbid conditions that impact outcomes. We examined racial differences in comorbidities among patients with HF and the mediating role of social determinants of health (SDOH). Hypothesis: Comorbidities among people hospitalized with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) will differ by race, and SDOH will partly explain the disparities. 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 (n = 506 HFpEF and 742 HFrEF, 4.1% of the REGARDS cohort) were included in this cross-sectional analysis. Comorbidities were abstracted from HF hospitalization records. We estimated age- and sex-adjusted prevalence ratios (PR) for comorbidities comparing Black to White participants. Guided by the Healthy People’s 2030 framework, SDOH including income, education, marital status, rural residence, ZIP code-level poverty, healthcare provider shortage area and poor public infrastructure were considered as potential mediators using the inverse odds weighting method. Results: Among participants with a HF hospitalization, the median age was 79 (IQR: 73 – 85) years and 74 (67 – 80) years for White and Black adults, respectively. There were racial differences in the prevalence of some comorbidities between Black and White participants (Table). In HFpEF, low income and education explained 27% of the excess diabetes experienced by Black adults compared to White adults (P < 0.05). There was no significant mediation of other associations by SDOH. Conclusions: There were racial differences in the patterns of comorbidities among REGARDS participants with HF, with low income and education partly explaining the higher prevalence of diabetes among Black adults with HFpEF.

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, 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.

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 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.

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.

Introduction: Cardiometabolic diseases (CMDs) are prevalent among middle-aged and older people living with HIV (OPLWH), particularly in the Deep South. However, the role CMDs play on quality-of-life outcomes among OPLWH remain understudied. Purpose: The purpose of this observational study was to examine the association between CMDs and physical health-related quality of life (P-HRQOL) and quality of sleep among PLWH in the Deep South. Methods: This cross-sectional study included N=261 HIV-infected participants aged 40+ recruited from a University HIV/AIDS clinic located in the Southeastern United States. CMDs were self-reported and consisted of hypertension, heart failure, stroke, diabetes mellitus, Angina due to heart disease, and high cholesterol. P-HRQOL and sleep quality scores were obtained using the Medical Outcome Study HIV Health Survey (MOS-HIV) and Pittsburgh sleep quality index (PSQI). We performed regression analyses (adjusting for demographic confounders and depression) for each outcome to assess the association between CMDs and P-HRQOL and sleep quality among OPLWH. Results: The average age of participants was 51.10 ± 6.78, with 82.8% being non-white and 35.6% being males. The overall prevalence of having ≥ 1CMD was 64.4% (High cholesterol: 52.8%; Diabetes Mellitus: 22.8%; Stroke: 5.68%; Angina/chest pain: 4.5%; Heart Failure: 6.8%; Hypertension 84%). P-HRQOL scores were significantly lower in PLWH with ≥1 CMD compared to the non-CMD group (45.53 ± 11.54 Vs. 49.67 ± 10.77, p Conclusion: In a sample of PLWH in the Deep South, the presence of CMDs increased the risk for poor P-HRQOL and greater sleep disturbances. Interventions that focus on targeting P-HRQOL and sleep quality in OPLWH with CMDs are necessary to improve long-term outcomes.

Disruption of the skeletal muscle circadian clock leads to a preferential shift towards lipid oxidation, while reducing carbohydrate oxidation. These effects are apparent at the whole-body level, including glucose intolerance, increased energy expenditure, and fasting hyperglycemia. We hypothesize that exercise counters these metabolic disturbances by modifying the skeletal muscle clock and reverting substrate metabolism back towards an optimal substrate balance.

BACKGROUND: Intestinal (i.e. “gut”) permeability may be related to cardiovascular disease (CVD) risk, but biomarkers for gut permeability are limited and associations with CVD risk are unknown -particularly among older adults. AIMS: This cross-sectional study aimed to determine if serum biomarkers related to gut permeability [intestinal fatty acid-binding protein (iFABP)] and bacterial toxin clearing [cluster of differentiation 14 (CD14), lipopolysaccharide binding protein (LBP)] are associated with CVD risk among older adults. METHODS: Older adults (n = 74, 69.6 ± 6.5 years old) were stratified by CVD risk category. One-way ANOVAs determined differences in each biomarker by risk category, and associations with risk score were evaluated with Pearson correlations. RESULTS: LBP (p = 0.007), but not iFABP and CD14, was significantly different between CVD risk categories. Post-hoc tests indicated LBP was higher in moderate risk and high-moderate risk compared to the high risk category (p < 0.005). Evaluation of LBP and individual components in the risk score demonstrated a moderate, negative correlation of LBP with age and systolic blood pressure (r = −0.335 and r = −0.297) and a small positive correlation between LBP and total cholesterol and LDL cholesterol (r = 0.204 and r = 0.220). DISCUSSION/CONCLUSION: Lower risk for CVD was associated with higher circulating concentrations of LBP, lower iFABP, and lower systemic inflammation in older adults. Further, there were small positive relationships between total and LDL cholesterol and circulating levels of LBP. These data suggest LBP may be a key component in reducing CVD risk in older adults.

To (1) investigate the efficacy of multiple doses of an orally delivered probiotic bacteria Lactobacillus paracasei (LP) modified to express angiotensin (1–7) (LP-A) in altering physiologic parameters relevant to the gut-brain axis in older rats and to (2) compare this strategy with subcutaneous delivery of synthetic Ang(1–7) peptide on circulating Ang(1–7) concentrations and these gut-brain axis parameters. Male 24-month-old F344BN rats received oral gavage of LP-A, or subcutaneous injection of Ang(1–7) for 0×, 1×, 3×, or 7×/week over 4 weeks. Circulating RAS analytes, inflammatory cytokines, and tryptophan and its downstream metabolites were measured by ELISA, electrochemiluminescence, and LC-MS respectively. Microbiome taxonomic analysis of fecal samples was performed via 16S-based PCR. Inflammatory and tryptophan-related mRNA expression was measured in colon and pre-frontal cortex. All dosing regimens of LP-A induced beneficial changes in fecal microbiome including overall microbiota community structure and α-diversity, while the 3×/week also significantly increased expression of the anti-inflammatory species Akkermansia muciniphila. The 3×/week also increased serum serotonin and the neuroprotective analyte 2-picolinic acid. In the colon, LP-A increased quinolinate phosphoribosyltransferase expression (1×/week) and increased kynurenine aminotransferase II (1× and 3×/week) mRNA expression. LP-A also significantly reduced neuro-inflammatory gene expression in the pre-frontal cortex (3×/week: COX2, IL-1β, and TNFα; 7×/week: COX2 and IL-1β). Subcutaneous delivery of Ang(1–7) increased circulating Ang(1–7) and reduced angiotensin II, but most gut-brain parameters were unchanged in response. Oral—but not subcutaneous—Ang(1–7) altered physiologic parameters related to gut-brain axis, with the most effects observed in 3×/week oral dosing regimen in older rats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00196-y) contains supplementary material, which is available to authorized users.

Aging is a multifactorial process characterized by progressive changes in gut physiology and the intestinal mucosal immune system. These changes, along with alterations in lifestyle, diet, nutrition, inflammation and immune function alter both composition and stability of the gut microbiota. Given the impact of environmental influences on the gut microbiota, animal models are particularly useful in this field. To understand the relationship between the gut microbiota and aging in nonhuman primates, we collected fecal samples from 20 male and 20 female rhesus macaques (Macaca mulatta), across the natural macaque age range, for 16S rRNA gene analyses. Operational taxonomic units were then grouped together to summarize taxon abundance at different hierarchical levels of classification and alpha- and beta-diversity were calculated. There were no age or sex differences in alpha diversity. At the phylum level, relative abundance of Proteobacteria and Firmicutes and Firmicutes to Bacteriodetes ratio were different between age groups though significance disappeared after correction for multiple comparisons. At the class level, relative abundance of Firmicutes_Bacilli decreased and Proteobacteria_Alphaproteobacteria and Proteobacteria_Betaproteobacteria increased with each successively older group. Only differences in Firmicutes_Bacilli remained significant after correction for multiple comparisons. No sex differences were identified in relative abundances after correction for multiple comparisons. Our results are not surprising given the known impact of environmental factors on the gut microbiota.

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.

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.

Hypertension has been linked with peripheral and central reductions in vascular density, and with devastating effects on brain function. However, the underlying mechanisms in the relationship between blood pressure and cognitive impairment have yet to be fully elucidated. Here, we review compelling evidence from two lines of inquiry: one that links microvascular rarefaction with insulin-like growth factor 1 (IGF-1) deficiencies, and another which posits that vascular dysfunction precedes hypertension. Based on the findings from experimental and clinical studies, we propose that these lines of evidence converge, and suggest that age-related declines in IGF-1 concentrations precede microvascular rarefaction, initiate an increase in vascular resistance, and therefore are causally linked to onset of hypertension. Physical exercise provides a relevant model for supporting our premise, given the well-established effects of exercise in attenuating vascular dysfunction, hypertension, IGF-1 deficiency, and cognitive decline. We highlight here the role of exercise-induced increases in blood flow in improving vascular integrity and enhancing angiogenesis via the actions of IGF-1, resulting in reversal of rarefaction and hypertension, and enhancement of cerebral blood flow and cognition.

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 x 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.

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.

In recent years a number of beneficial health effects have been ascribed to the renin-angiotensin system (RAS) that extend beyond lowering blood pressure, primarily mediated via the angiotensin-converting enzyme-2 (ACE2)/angiotensin (1–7) or Ang(1–7)/MAS receptor axis. Moreover, once thought as merely a systemic effector, RAS components exist within tissues. The highest tissue concentrations of ACE2 mRNA are located in the gut making it an important target for altering RAS function. Indeed, genetically engineered recombinant probiotics are promising treatment strategies offering delivery of therapeutic proteins with precision. An Ang(1–7) secreting Lactobacillus paracasei (LP) or LP-A has been described for regulation of diabetes and hypertension; however, we are the first to the best of our knowledge to propose this paradigm as it relates to aging. In this Research Practice manuscript, we provide proof of concept for using this technology in a well-characterized rodent model of aging: the Fisher344 x Brown Norway Rat (F344BN). Our primary findings suggest that LP-A increases circulating levels of Ang(1–7) both acutely and chronically (after 8 or 28 treatment days) when administered 3× or 7×/week over 4 weeks. Our future preclinical studies will explore the impact of this treatment on gut and other age-sensitive distal tissues such as brain and muscle.

Background 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.

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.