Physical Phenotype Research Articles

Overlapping and Distinct Physical and Biological Phenotypes in Pure Frailty and Obese Frailty.

Pure frailty and obese frailty are common types of frailty syndrome. However, the overlapping and distinct characteristics between pure frailty and obese frailty remain unclear. This study aims to reveal the overlapping/distinct physical and biological phenotypes of pure frailty and obese frailty, providing theoretical support for their prevention, diagnosis, and treatment. Mice were fed either a normal or high-fat diet and assessed at 20 months of age. They were assigned to one of the four groups: control, obesity, pure frailty, and obese frailty. Grip strength, walking speed, physical activity, endurance, and body weight were measured to determine pure frailty and obese frailty. Physical and biological phenotypes were assessed. Distinct physical phenotypes were observed between pure frailty and obese frailty in terms of body weight, lean mass, fat mass, fat mass in tissue, grip strength, endurance, and physical activity, while walking speed overlapped. In biological phenotypes, levels of Smad2/3, FoxO3a, P62, LAMP-2, and cathepsin L expression were distinct, while AKT, p-AKT, mTOR, p-mTOR, p-Smad2/3, p-FoxO3a, Beclin-1, ATG7, and LC3 overlapped. Distinct physical phenotypes observed in obese frailty are primarily attributable to the effect of obesity, with further impairment of muscle function resulting from the combined effects of frailty syndromes and obesity. Pure frailty and obese frailty share overlapping biological phenotypes, particularly in the regulation of muscle protein synthesis. Moreover, the interaction between obesity and frailty syndromes gives rise to both overlapping and distinct biological phenotypes, especially in the regulation of specific degradation signaling proteins.

The mitochondrial function of peripheral blood mononuclear cells in frail older patients

BackgroundFrailty increases the incidence of geriatric syndromes and even the risk of death in old adults. However, the diagnostic criteria for frailty are inconsistent because of complex pathological processes and diverse clinical manifestations. To determine the effective biomarker and recognize frail status early, we investigated the correlation of mitochondrial morphology and function of human peripheral blood mononuclear cells (PBMCs) with frailty status in older adults. MethodsThis Cross-sectional study followed 393 participants (aged 25–100 years, female 31.04 %) from the First Affiliated Hospital of Nanjing Medical University. The frailty status of subjects was assessed by the physical frailty phenotype (PFP) scale. We analyzed mitochondria functions including mitochondria copy number (mtDNAcn), the mRNA expressions of mitochondrial dynamics-related genes mitofusin 1(MFN1), mitofusin 2(MFN2), optic atrophy protein-1(OPA1), fission protein-1(FIS1) and dynamin-related protein 1(DRP1), mitochondrial oxidative respiration and reactive oxygen species(ROS) levels in PBMCs. Mitochondria morphology, size, and number were observed by transmission electron microscopy (TEM). ResultsAfter adjustment for sex and BMI, mtDNAcn, the mRNA expression of FIS1, mitochondrial respiratory function (proton leak, maximum oxygen consumption, and respiratory reserve) and ROS level were significantly correlated with age (P = 0.031, 0.030, 0.042, 0.003, 0.002, 0.022, respectively). After correcting for age, sex, and BMI, mtDNAcn and the mRNA expression of OPA1 were correlated with 4 m gait speed respectively (P = 0.003, 0.028, respectively). Compared with non-frail people, mtDNAcn, the mRNA expression of MFN1, mitochondrial basal respiration, proton leak, maximum oxygen consumption, ATP production and space capacity were significantly decreased in frail older adults (P = 0.013, 0.036, 0.026, 0.024, 0.012, 0.032, 0.020, respectively). ROS levels were significantly increased in the frail group (P = 0.016). Compared with non-frail people, the number, length, and perimeter, area of mitochondria were reduced in frail group under TEM (all P < 0.001). ConclusionMitochondrial dysfunctions (decreased mtDNAcn, impaired mitochondrial morphology, imbalanced mitochondrial dynamic, impaired mitochondrial respiratory function, and increased ROS levels) were significantly correlated with frail status.

Creatinine-to-cystatin C ratio and frailty in older adults: a longitudinal cohort study

BackgroundCreatinine-to-cystatin C ratio (CCR) has been associated with multiple adverse outcomes. However, little is known about its relationship with frailty. We aimed to explore the association between CCR and frailty among older adults.MethodsA total of 2599 participants aged ≥ 60 years (mean age 67.9 ± 6.0 years, 50.4% males) were included from the China Health and Retirement Longitudinal Study (2011–2015). Baseline CCR was calculated as plasma creatinine (mg/dL) / cystatin C (mg/L) × 10 and was grouped by quartiles. Frailty was evaluated by the validated physical frailty phenotype (PFP) scale and was defined as PFP score ≥ 3. The generalized estimating equations model was used to explore the relationship between CCR and frailty.ResultsThe frailty risk decreased gradually with increasing CCR in the quartiles (P for trend = 0.002), and the fourth CCR quartile was associated with a significantly lower risk of frailty compared with the lowest quartile (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19–0.70). When modeling as a continuous variable, per 1-unit increase in CCR was related to 17% decreased odds of frailty (OR 0.83, 95% CI 0.74–0.93). The association was consistent in male and female participants (P for interaction = 0.41). Poisson models revealed that frailty score was negatively associated with CCR (β= -0.11, 95% CI= -0.19 to -0.04), and sex did not significantly moderate the associations (P for interaction = 0.22). The results were not affected by further adjusting for high-sensitivity C-reactive protein. Similar results were observed by analyses with multiple imputation technique and analyses excluding participants with baseline frailty.ConclusionsHigher CCR was associated with a lower frailty risk. CCR may be a simple marker for predicting frailty in older adults.

Examining the Cycle of Physical Frailty in Falls Clinic Attendees Through Structural Equation Modeling.

In 1998, Fried and Walston introduced the Cycle of Frailty (CF) as a foundational concept for defining the physical frailty phenotype (FP). While the FP has been extensively validated, the CF hypothesis lacks equivalent support. This study aimed to internally validate the CF using structural equation modeling (SEM) in a clinical dataset of adults aged 50 or older attending an outpatient falls clinic. Measures included: age, morbidity, nutrition, sarcopenia by bioelectrical impedance, VO2max, handgrip strength, basal metabolic rate (BMR), 5-times chair stand test (5CST), physical activity, and total energy expenditure (TEE). The SEM, incorporating CF hypothesized causal pathways, was tested using IBM® SPSS® Amos 27.0.0 (maximum likelihood method) with a sample of 102 adults (mean age 69.8 years, 58.8% women). Overall, the SEM was supported by the data (χ2 = 44.4, df = 37, p = 0.189), with significant (p < 0.05) regression weights for morbidity→sarcopenia, age→sarcopenia, sarcopenia→VO2max, sarcopenia→handgrip strength, handgrip strength→5CST, physical activity→TEE, TEE→nutrition, and BMR→TEE. However, nutrition→sarcopenia, sarcopenia→BMR, VO2max→5CST, and 5CST→physical activity were not significant. Although the SEM was limited by inclusion of surrogate CF measures (e.g., 5CST instead of gait speed, VO2max based on age-predicted maximal/resting heart rate), it provided some internal support for the CF hypothesis.

Physical Function and Mortality in Older Adults with Chronic Kidney Disease.

Accurate mortality prediction can guide clinical care for older adults with chronic kidney disease (CKD). Yet existing tools do not incorporate physical function, an independent predictor of death in older adults. We determined whether incorporating physical function measurements improve mortality prediction among older adults with CKD. We included Chronic Renal Insufficiency Cohort participants who were ≥65 years old, had estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2, not receiving kidney failure replacement therapy (KFRT), and had least one gait speed assessment. Gait speed was measured at usual pace (≥0.84, 0.83-0.65, 0.64-0.47, ≤0.46 meters/second, or unable), and frailty was assessed using Physical Frailty Phenotype criteria (range 0 to 5 points, also known as Fried criteria). We modeled time to all-cause death over five years using Cox proportional hazard models, treating KFRT as censored and non-censored events in separate analyses. C-statistics assessed model discrimination. Among 2,338 persons, mean age was 70±4 years; 43% were female and 43% were Black. Mean eGFR was 42±13 mL/min/1.73m2 and median urine albumin-to-creatinine ratio was 33 mg/g [Q1 9, Q3 206]. Over a median follow-period of 5 years, 392 died and 164 developed KFRT. In censored analyses, adding gait speed or frailty improved mortality risk prediction. The C-statistic changed from 0.69 to 0.72 with gait speed scores, and from 0.70 to 0.73 with frailty scores. The performance of models with gait speed or frailty was similar in non-censored analyses. Among older adults with CKD, adding measures of physical function modestly improves mortality prediction.

Prospective Cohort Study Examining the Ability of Performance-Based and Self-Reported Frailty Measures to Predict 30-Day Rehospitalizations After Kidney Transplantation.

Performance-based measures of frailty are associated with healthcare utilization after kidney transplantation (KT) but require in-person assessment. A promising alternative is self-reported frailty. The goal of this study was to examine the ability of performance-based and self-reported frailty measures to predict 30-day rehospitalizations after KT. We conducted a prospective, observational cohort study involving 272 adults undergoing KT at Mayo Clinic in Minnesota, Florida, or Arizona. We simultaneously measured frailty before KT using the physical frailty phenotype (PFP), the short physical performance battery (SPPB), and self-report (the Patient-Reported Outcomes Measurement Information System [PROMIS] 4-item physical function short form v2.0). Both the PFP and self-reported frailty were independently associated with more than a 2-fold greater odds of 30-day rehospitalizations, while the SPPB was not. To our knowledge, this is the first study to assess the prognostic value of all three of the above frailty measures in patients undergoing KT. The PFP is more prognostic than the SPPB when assessing the risk of 30-day rehospitalizations; self-reported frailty can complement the PFP but not replace it. However, the 4-item survey assessing self-reported frailty represents a simple way to identify patients undergoing KT surgery who would benefit from interventions to lower the risk of rehospitalizations.

Interventions to prevent the onset of frailty in adults aged 60 and older (PRAE-Frail): a systematic review and network meta-analysis.

Frailty in older adults is associated with multiple adverse health outcomes, while evidence on its successful prevention has been scarce. Therefore, we analyzed the effectiveness of different interventions for the prevention of frailty onset. In this systematic review, eight databases were searched for randomized controlled trials of interventions in non-frail (i.e., robust or pre-frail) adults aged ≥ 60years that assessed frailty incidence at follow-up. Additive component network meta-analysis (CNMA) was conducted to isolate the effect of different intervention types on the main outcome of frailty incidence, reporting relative risk (RR) with 95% confidence intervals (CI). The effect on gait speed was analyzed as an additional outcome using a classic network meta-analysis and the standardized mean difference (SMD) with 95% CI. We screened 24,263 records and identified 11 eligible trials. Nine trials (842 participants, all categorized according to the physical phenotype) in pre-frail (seven RCTs) and robust/pre-frail (two RCTs) older adults were included in the CNMA. Physical exercise significantly reduced frailty incidence at follow-up (RR 0.26, 95% CI 0.08; 0.83), while this was not found for nutritional interventions (RR 1.16, 95% CI 0.33; 4.10). Interventions based on physical exercise also improved gait speed (SMD 1.55, 95% CI 1.16; 1.95). In addition, 22 eligible trial protocols without published results were identified. Interventions based on physical exercise appear to be effective in preventing the onset of frailty in older adults. Although the available data are still limited, results from ongoing trials may add to the body of evidence in the foreseeable future.

Frailty in Hemodialysis Patient

Abstract Background Frailty has been defined as a state of increased vulnerability to stressors as a consequence of degeneration in multiple systems. There remain two schools of thought with regard to frailty: one which sees frailty as a physical phenotype characterized by sarcopenia and another that views frailty as an accumulation of deficits across a variety of domains. Aim of the Work The aim of this study was to assess the prevalence of frailty among dialysis population. Patients and Methods This cross section study carried out in Hemodialysis Unit of the Nasr City Health Insurance Hospital between October 2020 and July 2021. The total number of the study was 325 hemodialysis patients, 25 were excluded from the study, thus the enrolled final number became 300 hemodialysis patients on maintenance hemodialysis therapy for at least 6 months. Results The mean age of the patients was 45.57±11.79 years (range 25-65 years) 50% of them were under 45 years of age. 258 (86%) of patients were males and 42 (14%) females, with male to female ratio about 6.14:1. 37 patients (12.3%) has positive HCV, while the results also show that none of the HBV and HIV of the study group. 10 patients (3.3%) of vulnerable, 89 (29.7%) patients at mild frailty, table also clarified that, 126 (42.0%) patients at moderat4e frailty, furthermore, 75 (25%) patients at severe frailty in Edmonton frail scale. There was significant positive association between frailty and age with p-value &amp;lt;0.001. Males more affected by frailty than females. Conclusion The differences in the frailty prevalence among CKD patients could be caused by the different definitions of frailty that each study adopted. It is important to prevent early-onset disability in end-stage renal disease, which may be accelerated by frailty in this patient population, which includes individuals who already carry a high risk of morbidity and mortality. We adopted the Edmonton Frail Scale (EFS) based on self-report, it is very simple to administer and can be carried out by hemodialysis nursing staff after minimal training, without the need for specialist medical staff, in less than 15 min. Its association with poor short-term outcome highlights its utility in detecting frail patients, but because it is a multi-domain test, it also gives health professionals information about which areas of frailty are affected. This would allow specialists to administer specific, more complex scales to detect deficits in independence for basic and instrumental activities of daily life, cognition, emotional status, and social support. Our findings allow us to recommend the inclusion of the frailty comprehensive assessment of patients starting the dialysis program to timely identification of frailty syndrome.

Head motion in the UK Biobank imaging subsample: longitudinal stability, associations with psychological and physical health, and risk of incomplete data.

Participant motion in brain magnetic resonance imaging is associated with processing problems including potentially non-useable/incomplete data. This has implications for representativeness in research. Few large studies have investigated predictors of increased motion in the first instance. We exploratively tested for association between multiple psychological and physical health traits with concurrent motion during T1 structural, diffusion, average resting-state and task functional magnetic resonance imaging in N = 52 951 UK Biobank imaging subsample participants. These traits included history of cardiometabolic, inflammatory, neurological and psychiatric conditions, as well as concurrent cognitive test scores and anthropometric traits. We tested for stability in motion in participants with longitudinal imaging data (n = 5305, average 2.64 years later). All functional and T1 structural motion variables were significantly intercorrelated (Pearson r range 0.3-0.8, all P < 0.001). Diffusion motion variables showed weaker correlations around r = 0.1. Most physical and psychological phenotypes showed significant association with at least one measure of increased motion including specifically in participants with complete useable data (highest β = 0.66 for diabetes versus resting-state functional magnetic resonance imaging motion). Poorer values in most health traits predicted lower odds of complete imaging data, with the largest association for history of traumatic brain injury (odds ratio = 0.720, 95% confidence interval = 0.562 to 0.923, P = 0.009). Worse psychological and physical health are consistent predictors of increased average functional and structural motion during brain imaging and associated with lower odds of complete data. Average motion levels were largely consistent across modalities and longitudinally in participants with repeat data. Together, these findings have implications for representativeness and bias in imaging studies of generally healthy population samples.

The association between olfactory subdomains and frailty: A prospective case‒control study investigation.

Amidst the rise of frailty among a globally aging population, olfactory decline has emerged as a harbinger of frailty and mortality in population-level studies. However, the relationships between frailty and the olfactory subdomains of identification (OI), discrimination (OD), and threshold (OT) remain unexplored. This study prospectively examined the association between olfactory subdomains and the physical frailty phenotype (PFP) to investigate olfactory evaluation as a means of frailty screening. A case‒control study of 45 frail and 45 non-frail individuals matched by age and sex. OT, OD, OI (range 0‒16), and composite sum (threshold, discrimination, and identification scores [TDI], range 0‒48) were measured with Sniffin' Sticks. PFP was defined by presence of three or more criteria: physical inactivity, self-reported exhaustion, muscle weakness, slow gait, and unintentional weight loss. Conditional logistic regression evaluated associations between olfactory subdomains and frailty. Ninety individuals with mean age of 83.1±4.9 years, 60% female (n=54), and 87.8% white (n=79) were included. Olfactory scores were significantly lower in the frail group for OI (9.2vs. 12.1, p<0.001), OD (8.1vs. 11.6, p<0.001), OT (4.4vs. 8.5, p<0.001), and TDI (21.7vs. 32.2, p<0.001) than in the non-frail group. A single-point decrease in olfactory score was associated with increased odds of frailty in OT (odds ratio [OR]: 2.21, 95% confidence interval: [1.22, 3.98]), OD (OR: 2.19, 95% CI: [1.32, 3.65]), OI (OR: 2.29, 95% CI: [1.19, 4.39]), and TDI (OR: 1.54, 95% CI: [1.14, 2.08]). The robust association between olfactory subdomain scores and frailty suggests that olfaction may be an accessible signifier of frailty. Future studies should investigate this relationship longitudinally to assess predictive relationships.

Associated Congenital Abnormalities and Physical Phenotype in Patients with Diamond-Blackfan Anemia May Be Overlooked.

Diamond-Blackfan anemia (DBA) is a rare and inherited form of erythroid aplasia, characterized by severe macrocytic anemia, congenital malformations, and predisposition to cancer. The purpose of this study is to determine the congenital abnormalities and dysmorphological features of DBA patients in a cross-sectional manner. The study group included patients who had diagnosis of DBA between 1983 and 2017. Dysmorphological examinations of the patients were performed by an experienced dysmorphologist and also echocardiography and abdominal ultrasonography were performed in order to figure out cardiac and urogenital abnormalities. A total of 45 patients were examined in this study. Dysmorphological examination, echocardiography, and abdominal ultrasonography revealed the rate of congenital abnormalities as high as 88.7%. In consideration of the congenital abnormalities, the most common findings were craniofacial, followed by skeletal abnormalities. The rate of anomalies was found higher in our series of patients than that have been previously reported, most probably due to the evaluations being performed by a dysmorphologist in our cohort and not only depending on patient records or hematologists' physical examination.

Effects of (pre)frailty and cognitive reserve on mild cognitive impairment among community-dwelling older adults

ObjectiveWe aimed to identify the effect of lifespan cognitive reserve and (pre)frailty on mild cognitive impairment (MCI) among older adults. Materials and methodsA total of 4420 older adults aged above 60 with intact cognition recruited in 2011/2012 were followed up in 2015 from the China Health and Retirement Longitudinal Study (CHARLS). The assessment of MCI was based on executive function, episodic memory, and visual-spatial ability. (Pre)frailty was assessed by the validated version of the Fried physical frailty phenotype scale. The lifespan cognitive reserve consisted of the highest educational level, occupational complexity, and participation in leisure activities. Modified Poisson regression models were used to identify the risk of MCI in relation to (pre)frailty and lifespan cognitive reserve index. We examined the interactions of (pre)frailty and lifespan cognitive reserve index on both additive and multiplicative scales. ResultsBaseline (pre)frailty significantly increased the risk of MCI after 3–4 years of follow-up, and high cognitive reserve protected individuals from the risk of MCI. There was an additive interaction between (pre)frailty and the low lifespan cognitive reserve (the relative excess interaction risk=1.08, 95 % CI= 0.25–1,91), but no multiplicative interaction (RR=0.95, 95 % CI= 0.67–1.37). The risk of MCI was larger among older adults with comorbid (pre)frailty and low cognitive reserve than those with each condition alone. ConclusionCognitive reserve attenuates the risk of MCI associated with (pre)frailty. This finding implicates the urgency for identifying and managing MCI among frail older adults who accumulate low cognitive reserve in the life course.

Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. Among participants aged ≥ 60years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

The Association between Physical Frailty and Cognitive Performance in Older Adults Aged 60 to 96 Years: Data from the "Good Aging in Skåne" (GÅS) Swedish Population Study.

The association between physical frailty and performance in different cognitive domains in the absence of cognitive disorders is poorly understood. Hence, we aimed to explore the associations between frailty levels based on the Fried Physical Frailty Phenotype and performance of different cognitive domains. We also aimed to examine the associations between cognitive function and each criterion in the Fried Frailty Scale using the same cognitive domains in a non-dementia population aged 60-96 years. This cross-sectional study included 4,329 participants aged 60-96 years, drawn from the "Good Aging in Skåne" population study. Frailty indices included handgrip strength, physical endurance, body mass index (BMI), physical activity, and walking speed. Cognitive function was assessed across eight domains: episodic memory, processing speed, semantic memory, verbal fluency, working memory, attention, executive function, and visual perception. We constructed adjusted multiple linear regression models for each cognitive domain, with the frailty levels as the independent variable. Likewise, we constructed linear regression models with each cognitive domain as the dependent variable and frailty criteria as independent variables. Physical frailty was associated with poor performance in episodic memory, processing speed, semantic memory, verbal fluency, working memory, attention, and executive functions (p&lt;0.001 for all associations). Weaker hand grip strength was independently associated with poorer performance in all cognitive domains (p &lt; 0.015). Higher levels of frailty were associated with poorer performance in all cognitive domains except visual perception. Describing frailty by considering cognitive functioning may provide a better understanding of frailty.

Differential relationships between physical activity and pain phenotypes in individuals with spinal cord injury

Background Chronic pain affects 70% of individuals with spinal cord injury (SCI) and leads to declines in health and quality of life. Neuropathic and nociceptive pain are phenotypes derived from different mechanisms that contribute to pain perception. The objective of this research was to investigate differential pain responses to moderate-to-vigorous physical activity (MVPA) in two chronic pain phenotypes: neuropathic and nociceptive pain. Methods Community-based physical activity levels were collected for one week in 17 individuals with SCI using a wrist-worn accelerometer, and daily pain ratings were assessed and categorized by phenotype. Physical activity levels were summarized to calculate minutes of MVPA. Correlational analyses were conducted to compare relationships between pain intensity and MVPA across individual participants and between pain phenotype groups. Results The neuropathic pain group revealed significant negative correlation between MVPA and pain intensity. In the nociceptive pain group, there was no significant correlation between MVPA and pain intensity. Further analysis revealed two subgroups of positive (N = 4) and negative (N = 3) correlations between MVPA and pain intensity. Pain location differed between the subgroups of nociceptive pain. Individuals with negative correlation experienced neck and upper back pain, whereas individuals with positive correlation experienced unilateral upper extremity pain. Conclusion Differential relationships exist between pain phenotypes and MVPA in individuals with SCI. Pain location differed between the subgroups of nociceptive pain, which we presume may indicate the presence of nociplastic pain in some individuals. These results may contribute to the advancement of personalized pain management by targeting non-pharmacological interventions for specific pain phenotypes. Trial registration: ClinicalTrials.gov identifier: NCT05236933..

FRAIL scale as a screening tool and a predictor of mortality in non-dialysis dependent patients.

This study aimed to compare the diagnostic yield of the FRAIL scale with respect tothe physical frailty phenotype measure and their association with mortality in non-dialysis-dependent patients. In this prospective cohort study, non-dialysis dependent patients with chronic kidney disease (CKD) stages 3b-5 seen in the nephrology outpatient clinics of two university hospitals were included. The presence of frailty was evaluated by physical frailty phenotype measure and the FRAIL scale. Patients were evaluated for six months, and mortality was recorded. The Kappa test was used to evaluate the diagnostic properties between the methods, and logistic regression to test the association between frailty and mortality. One hundred fifty-three patients were evaluated; average age was 65 (56-70) years, 50.9% were women, and the all-cause mortality rate was 2.6%. Forty-six patients were classified as living with frailty according to the physical frailty phenotype while 36patients were rated frail by the FRAIL scale. In adults < 60years of age, the FRAIL scale showed good accuracy (84.9%) and specificity (93.2%) but had low sensitivity (41.3%) and moderate agreement (Kappa = 0.41; p < 0.001) compared to the definition of thephysical frailtyphenotype.The adjusted logistic regression model showedthat the patients with frailty assessed by the FRAIL scale had a greater chance of mortality than the non-frail patients (OR: 6.8; CI95%:1.477-31.513; p = 0.014). Physical frailty phenotype identifies more patients as having pre-frailty and frailty in non-dialysis dependent patientsas compared to the FRAIL scale. However, the FRAIL scale is a simple bedside tool that can be useful for screening forfrailty and whose results were associated with mortality.

Abstract 273: Extrinsic photoaging vs intrinsic aging in dermal fibroblasts: Its impact on the microenvironment and melanoma progression

Abstract Melanoma is the deadliest form of skin cancer, with chronological aging as a major negative prognostic factor due to the influence of intrinsic aging on the tumor microenvironment (TME) to promote tumor initiation and progression. Ultraviolet radiation (UVR) exposure, which is a major risk factor for melanoma, also can cause a physical premature aging phenotype, known as extrinsic photoaging, from chronic UVA irradiation of the underlying dermis. Photoaging of the skin often occurs in tandem with chronological aging, and contributes to similar physical alterations in normal skin structure. However, the molecular mechanisms of how photoaging compares to chronological aging in changing the TME and on tumor progression is still lacking. Here we found that extrinsically photoaged fibroblasts have a higher level of secretion of lysosomal proteases, Cathepsins, which have been shown to be secreted via lysosomal exocytosis and play a functional role in extracellular matrix (ECM) remodeling at neutral PH levels. We found that Cathepsins B and D are secreted at higher levels in both extrinsically photoaged young fibroblasts and in intrinsically aged fibroblasts and upregulated at the endogenous protein level. Cathepsin B has been shown to be highly expressed in metastatic but not primary melanoma patient samples, and cleaves ECM proteins such as fibronectin and tenascin. Immunofluorescent staining of in-vitro fibroblast derived matrices (CDMs) confirmed that photoaging disrupts subsequent deposited extracellular matrix proteins similarly to that of intrinsically aged healthy fibroblasts and these matrix changes influences the growth pattern of melanoma lines plated on these CDMs. Mass spectrometry analysis of secreted proteomics confirmed that aged fibroblasts secrete more cathepsins than intrinsically young fibroblasts, and Cathepsins B and D were also detected in extracellular vesicle (EV) cargo proteomics. Single-Particle Interferometric Reflectance Imaging (SP-IRIS) of EVs showed that UVA irradiation induced a significant increase in the total number of secreted of exosomes and in expression of tetraspanin protein CD63, which plays a role in cargo sorting and has been detected in high levels in the plasma of melanoma patients. We hypothesize that extrinsic photoaging of fibroblasts induces the secretion of exosomes packaged with Cathepsins that play an integral role in ECM remodeling and matrix degradation in a beneficial manner for melanoma invasion. Further studies will assess the influence on secreted cathepsins on melanomagenesis and melanoma invasion through both mechanical and biochemical changes in the TME with in-vitro and in-vivo studies. Citation Format: Vania Wang, Yash Chhabra, Laura Hueser, Ashani Weeraratna. Extrinsic photoaging vs intrinsic aging in dermal fibroblasts: Its impact on the microenvironment and melanoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 273.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: V. Physical examination standards in endometriosis research

The World Endometriosis Research Foundation established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, 4 data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards underwent multiple rounds of iterations and revisions. N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of back and pelvic girdle; abdomen including allodynia and trigger points; vulva including provoked vestibulodynia; pelvic floor muscle tone and tenderness; tenderness on unidigital pelvic examination; presence of pelvic nodularity; uterine size and mobility; presence of adnexal masses; presence of incisional masses; speculum examination; tenderness and allodynia at an extra-pelvic site (e.g., forearm); and recording of anthropometrics. The EPHect-PE standards will facilitate the standardized documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.

Association between physical frailty, circadian syndrome and cardiovascular disease among middle-aged and older adults: a longitudinal study

BackgroundPhysical frailty (PF) and circadian syndrome (CircS) are proposed as novel risks for cardiovascular disease (CVD), but little attention is paid to their combined impact on CVD. This study aimed to investigate the association of PF, CircS and CVD in middle-aged and older adults.MethodsThe sample comprised 8512 participants aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS) 2011. PF was examined by the physical frailty phenotype scale. CircS was assessed by the components of the International Diabetes Federation (IDF) MetS plus short sleep duration and depression. The cut-off for CircS was set as ≥ 4. CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. A total of 6176 participants without CVD recruited from CHARLS 2011 and were followed up in 2018.ResultsThe prevalence of CVD in total populations, neither CircS or PF, PF alone, CircS alone and both CircS and PF were 13.0%, 7.4%, 15.5%, 17.4%, and 30.2%, respectively. CircS was more likely to be PF [OR (95%CI): 2.070 (1.732 ∼ 2.472)] than those without CircS. Both CircS alone [OR (95% CI): 1.954 (1.663 ∼ 2.296)], and coexisting CircS and PF [3.508 (2.739 ∼ 4.494)] were associated with CVD. Longitudinal analysis showed that individuals with both CircS and PF (HR: 1.716, 95%CI: 1.314 ∼ 2.240) and CircS alone [1.520 (1.331 ∼ 1.737)] were more likely to have new onset CVD than neither CircS or PF peers.ConclusionPF and CircS together are associated with higher CVD risk, which provided new evidence for a strong relation that warrants attention to assessing PF and CircS and in community to promote healthy aging.

Metabolic dysfunction and the development of physical frailty: an aging war of attrition.

The World Health Organization recently declared 2021-2030 the decade of healthy aging. Such emphasis on healthy aging requires an understanding of the biologic challenges aging populations face. Physical frailty is a syndrome of vulnerability that puts a subset of older adults at high risk for adverse health outcomes including functional and cognitive decline, falls, hospitalization, and mortality. The physiology driving physical frailty is complex with age-related biological changes, dysregulated stress response systems, chronic inflammatory pathway activation, and altered energy metabolism all likely contributing. Indeed, a series of recent studies suggests circulating metabolomic distinctions can be made between frail and non-frail older adults. For example, marked restrictions on glycolytic and mitochondrial energy production have been independently observed in frail older adults and collectively appear to yield a reliance on the highly fatigable ATP-phosphocreatine (PCr) energy system. Further, there is evidence that age-associated impairments in the primary ATP generating systems (glycolysis, TCA cycle, electron transport) yield cumulative deficits and fail to adequately support the ATP-PCr system. This in turn may acutely contribute to several major components of the physical frailty phenotype including muscular fatigue, weakness, slow walking speed and, over time, result in low physical activity and accelerate reductions in lean body mass. This review describes specific age-associated metabolic declines and how they can collectively lead to metabolic inflexibility, ATP-PCr reliance, and the development of physical frailty. Further investigation remains necessary to understand the etiology of age-associated metabolic deficits and develop targeted preventive strategies that maintain robust metabolic health in older adults.