Identification of Potential Blood-Based Biomarkers for Frailty by Using an Integrative Approach.

INTRODUCTION: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive, and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty. METHODS: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA-sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65-90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study. RESULTS: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79-0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch's t test p < 0.001). CONCLUSION: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use.

Association between Circulating Levels of CXCL9 and CXCL10 and Physical Frailty in Older Adults.

INTRODUCTION: Dysregulation of pro-inflammatory chemokines is considered a potential mechanism for the development of age-related medical conditions such as frailty. However, evidence linking circulating chemokines with frailty remains lacking. MATERIALS AND METHODS: We performed a case-control study including 48 cases and 48 controls aged 65-90 years, using the National Center for Geriatrics and Gerontology outpatient registry data. Cases were outpatients with physical frailty and low habitual daily activity. Controls were robust outpatients who performed habitual daily activities. The Japanese version of the Cardiovascular Health Study criteria was used to diagnose physical frailty, and the modified Baecke questionnaire was used to evaluate habitual daily activities. Serum CXCL9 and CXCL10 levels were measured using enzyme-linked immunosorbent assay. RESULTS: The median age (interquartile range) in cases and controls was 78 (73-83) and 76 (72-80) years, with the proportions of men were 47.9% and 43.8%, respectively. In the logistic regression model with adjustment for age, sex, and other confounding factors, the multivariable odds ratios (95% confidence intervals) for the highest versus lowest tertile of CXCL9 and CXCL10 levels were 7.90 (1.61-49.80) and 1.61 (0.42-6.30), respectively. However, we did not observe a linear association between CXCL9 levels and physical frailty components. DISCUSSION/CONCLUSION: Our preliminary data exhibit that circulating CXCL9 levels were positively associated with the odds of physical frailty. However, these findings lack evidence of a dose-response relationship between CXCL9 levels and physical frailty components. Further research with a larger sample size is required to confirm these findings.

Preliminary gait analysis of frail versus older adults.

[Purpose] This study aimed to verify the usefulness of an inertial measurement unit and compare the gait of frail and robust older adults. [Participants and Methods] Six participants (three males and three females) in their 80s were diagnosed as frail or robust according to Japanese Cardiovascular Health Study criteria. Using an inertial measurement unit, we measured parameters associated with the sole clearance and center of gravity shift. We then calculated the margin of stability in two directions. [Results] The gait analysis of both groups was reliable, as intraclass correlation coefficient values were comparable to the measurement accuracy of the inertial measurement unit achieved in a previous study of young participants. The results revealed that the sole clearance during the swing phase tended to be lower in frail than robust participants; moreover, the center of mass shift tended to be small and step width wide in frail participants, whereas the center of mass shift tended to be large in robust participants. [Conclusion] Our findings are expected to contribute to gait training in rehabilitation programs for older frail adults, the development of welfare equipment such as walking aids for frail elderly individuals, and the establishment of the reliability of inertial measurement unit use.

Osteosarcopenia, the co-existence of osteoporosis and sarcopenia, is associated with social frailty in older adults.

BACKGROUND: Osteosarcopenia is a newly described, aging-associated condition. Social frailty is an important condition whose prevalence may have risen by physical distancing during the coronavirus disease 2019 pandemic. However, the relationship between these two remains unclear. AIMS: To examine the association between osteosarcopenia and social frailty. METHODS: This cross-sectional study was conducted using data from outpatients visiting general geriatric hospital frailty clinics. Bone mineral density (BMD) and muscle mass were measured using dual X-ray absorptiometry. Osteoporosis was defined as a BMD of < 70% of the young adult mean, according to the Japan Osteoporosis Society. Sarcopenia was diagnosed as per the Asian Working Group for Sarcopenia 2019 recommendation. Osteosarcopenia was defined as the co-existence of osteoporosis and sarcopenia. We defined social frailty using a questionnaire comprising four items: general resources, social resources, social behavior, and basic social needs. Ordinal logistic regression analysis was performed with social frailty status and osteosarcopenia as the dependent and independent variables, respectively. RESULTS: We included 495 patients (mean age = 76.5 ± 7.2 years) in the analysis; of these, 58.2% were robust and 17.2%, 13.5%, and 11.1% had osteoporosis alone, sarcopenia alone, and osteosarcopenia, respectively. Social frailty prevalence increased stepwise from 8.0% in robust patients to 11.8%, 17.9%, and 29.1% among those with osteoporosis alone, sarcopenia alone, and osteosarcopenia, respectively (P < 0.001). Logistic regression analysis revealed that only osteosarcopenia was significantly associated with social frailty (pooled odds ratio: 2.117; 95% confidence interval: 1.104-4.213). DISCUSSION: Comprehensive assessment of osteosarcopenia and social frailty is needed for disability prevention in older adults.

Diet-induced inflammation is associated with sarcopenia and muscle strength in older adults who visit a frailty clinic.

BACKGROUND: Diet-induced inflammation may be associated with sarcopenia; however, few reports have examined this relationship. AIM: To examine the association between the dietary inflammatory index (DII) and sarcopenia in older adults who visited a frailty clinic in Japan. METHODS: This cross-sectional study used outpatient data from the Frailty Registry Study. The DII is an index of diet-induced inflammation, and a dietary assessment was performed using a brief self-administered diet history questionnaire to calculate the DII score. We classified DII scores by quartiles (Q1-Q4), and sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus. Logistic regression analyses for sarcopenia were performed. Age, sex, comorbidities, and physical activity were entered as confounding factors (Model 1) and Models 2, 3, and 4 with BMI, protein intake, and energy intake added to Model 1. RESULTS: We included 304 patients in the analysis (mean age, 77.6 ± 6.3 years; female, 67.4%). The prevalence of sarcopenia was 14.5%. Logistic regression analyses showed that DII scores were significantly associated with sarcopenia in Model 1 and 2 (Model 1, reference: Q1, Q4: OR 3.10, P = 0.020; Model 2, Q4: OR 3.40, P = 0,022) but not in Model 3 and 4. DISCUSSION: Diet-induced inflammation is associated with a higher likelihood of sarcopenia; however, this association disappeared after confounding for protein and energy intake. CONCLUSIONS: The results demonstrated that dietary protein and energy parameters were the main drivers for muscle health in medical patients.

Evaluation of muscle quality and quantity for the assessment of sarcopenia using mid-thigh computed tomography: a cohort study.

BACKGROUND: For the diagnosis of Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP) revised the algorisms in 2019, where they added computed tomography (CT) as an assessment tool not only for quantity but also for quality in research purpose. However, the evidence for clinical appreciation of CT has been lacking. Therefore, we investigated the correlation between CT and various motor function tests to assess the utility of CT as a potential diagnostic tool for sarcopenia. METHODS: In total, 214 patients who were examined at our center during the study period (2016-2017) were included in the study. Single-slice CT scan of the mid-thigh region was performed, from which cross-sectional area (CSA) and CT attenuation value (CTV) of quadriceps femoris were evaluated for each subject. Other assessments included skeletal muscle mass index by DXA and BIA, muscle strength and physical performance. Furthermore, subjects were classified into four groups as per the Asia Working Group of Sarcopenia (AWGS) 2019 criteria as those with: normal, poor muscle function/strength (poor function), sarcopenia and severe sarcopenia. RESULTS: Knee muscle strength correlated with CSA (r = 0.60) and the correlation was significantly greater than that with DXA and BIA. For physical performance, standing-up test correlated with CSA (r = - 0.20) and CTV (r = - 0.40) and walking speed with CTV (r = 0.43), which was significantly greater than that with DXA and BIA. The CSA was significantly lower in women with sarcopenia group and in both men and women with severe sarcopenia (all p < 0.01). Furthermore, CTV was significantly lower in women with poor-function and in both men and women with severe sarcopenia group (all p < 0.01). CONCLUSIONS: CSA mostly correlated with muscle strength, whereas CTV mostly correlated with physical performance. CT with measurements of CSA and CTV enables the evaluation of muscle mass and quality simultaneously. CT is believed to be useful in inferring evaluation of motor function and assessment of sarcopenia.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.

BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Disuse Atrophy Accompanied by Intramuscular Ectopic Adipogenesis in Vastus Medialis Muscle of Advanced Osteoarthritis Patients.

Muscle dysfunction is the most important modifiable mediating factor in primary osteoarthritis (OA) because properly contracting muscles are a key absorber of forces acting on a joint. However, the pathological features of disuse muscle atrophy in OA patients have been rarely studied. Vastus medialis muscles of 14 female patients with OA (age range, 69 to 86 years), largely immobile for 1 or more years, were obtained during arthroplastic surgery and analyzed histologically. These were compared with female patients without arthritis, two with patellar fracture and two with patellar subluxation. Areas occupied by myofibers and adipose tissue were quantified. Large numbers of myofibers were lost in the vastus medialis of OA patients. The loss of myofibers was a possible cause of the reduction in muscle strength of the operated on knee. These changes were significantly correlated with an increase in intramuscular ectopic adipose tissue, and not observed in knees of nonarthritic patients. Resident platelet-derived growth factor receptor α-positive mesenchymal progenitor cells contributed to ectopic adipogenesis in vastus medialis muscles of OA patients. The present study suggests that significant loss of myofibers and ectopic adipogenesis in vastus medialis muscles are common pathological features of advanced knee OA patients with long-term loss of mobility. These changes may be related to the loss of joint function in patients with knee OA.

What is the best adjustment of appendicular lean mass for predicting mortality or disability among Japanese community dwellers?

BACKGROUND: Age-related declines in skeletal muscle mass and strength, representing "sarcopenia," are a growing concern in aging societies. However, the prevalence of low muscle mass based on the height2-adjustment has been shown to be extremely low, and a more appropriate definition of low muscle mass is needed, particularly for Asian women. The aim of this study was to explore the most appropriate adjustment of appendicular lean mass (ALM) for predicting mortality or disability risk using ALM or any of 5 adjustments of ALM among community-dwelling Japanese. METHODS: Subjects comprised 1026 men and 952 women between 40 and 79 years old at baseline (1997-2000) who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging, Japan. ALM (kg) and 5 adjusted indices of ALM (ALM/leg length, ALM/height, ALM/height2, ALM/weight, and ALM/body mass index [BMI]) were assessed at baseline. Disability was defined by long-term care insurance certification based on responses to a survey mailed in 2013, and death records were obtained as vital statistics until December 2014. Crude and adjusted Cox proportional hazard models were used to estimate hazard ratios for mortality or disability by sex-stratified quintiles of each ALM index (ALM and adjusted ALM) or sarcopenia-related indices. The area under the curve (AUC) was calculated with the multivariate-adjusted logistic regression model. Additionally, mixed-effects analyses were used to clarify the age-related ALM indices decline over 12 years (n = 1838). RESULTS: Crude Cox proportional hazard models and multivariate-adjusted logistic model (AUC) indicated that higher ALM and ALM/BMI in women, and higher ALM, ALM/leg length, ALM/height, and ALM/BMI in men were associated with lower risks for mortality or disability than ALM/height2. The mixed effect model indicated all ALM indices in men, and ALM, ALM/leg length, and ALM/height in women could better predict age-related lean muscle mass decline. CONCLUSIONS: Unadjusted ALM in women, and ALM/leg length, ALM/height, ALM/BMI, and ALM in men may be more appropriate for predicting future mortality or disability than ALM/height2. Considering the age-related muscle mass decline, unadjusted ALM would be the first variable to assess, regardless of sex, in this Japanese cohort study.

[Aging-related frailty and sarcopenia. Efficacy of osteoporosis treatment drugs for frailty and sarcopenia.]

Many of the adverse outcomes of frailty are probably mediated by sarcopenia. Unfortunately, there are currently no approved drug treatments for sarcopenia. Osteoporosis and sarcopenia are common in older age. A study on activated vitamin D revealed that muscle mass could be maintained by administering alfacalcidol to patients with osteoporosis. Bisphosphonate therapy, which is a gold standard for osteoporosis treatment, may help to maintain muscle mass.

[Pathological state or cause of sarcopenia.]

Skeletal muscle atrophy by aging(Sarcopenia)is more likely to occur in lower limbs rather than upper ones, and in the thigh rather than in the lower leg, and in the anterior side of thigh rather than posterior, faster in men than in women. It differs from disuse muscle atrophy in that it occurs slowly and gradually, hard to be recovered, or fast twitch fibers are mainly involved. Many factors or phenomena are known to contribute to proceed sarcopenia. In the aged skeletal muscle tissue, the number of satellite cells or motor neurons decrease and the function of the neuro-muscular junction declines. Oxidative stress and chronic inflammation increase as aging which relate with sarcopenia. Inflammatory cytokines, such IL-6, TNF-α, IL-5 play the roles Muscle protein breakdown is up regulated through ubiquitin-dependent proteolysis. Oxidative stress influences mitochondrial dysfunction or induces apoptosis. Also as aging, anabolic factors which are preferable to protein synthesis, such as IGF-1, sex hormones, vitamin D, or branched chain amino acid.

Sarcopenia and sarcopenic leg as potential risk factors for acute osteoporotic vertebral fracture among older women.

PURPOSE: Sarcopenia-related falls and fractures among women with osteoporosis are becoming an emerging problem because of rapid aging worldwide. We aimed to investigate the association between sarcopenia, given by the muscle mass of the arms and legs, and osteoporotic vertebral fracture (OVF) among female patients. METHODS: This cross-sectional study examined 216 women with fresh OVF (OVF group) diagnosed by magnetic resonance imaging and 1,608 women from an outpatient clinic who did not have a OVF [non-fracture (NF) group]. We performed whole-body dual-energy X-ray absorptiometry to analyze body composition, including skeletal muscle mass index (SMI; lean mass/height2) and bone mineral density (BMD). We used stepwise logistic regression analysis to determine the risk factors associated with OVF. RESULTS: After controlling for age, the OVF group showed lower appendicular SMI (5.62 vs. 5.97 kg/m2, P < 0.001), lower arm SMI (1.36 vs. 1.42 kg/m2, P = 0.004), lower leg SMI (4.27 vs. 4.55 kg/m2, P < 0.001), and higher prevalence of sarcopenia (42.3 vs. 25.9 %, P < 0.001), compared with the NF group. Reduced leg muscle mass and presence of sarcopenia were independent risk factors for acute OVF in multivariate analysis (odds ratio = 1.4, P = 0.002; odds ratio = 1.96, P < 0.001, respectively). CONCLUSIONS: We found higher prevalence of sarcopenia and lower leg muscle mass among patients with acute OVF compared with patients who did not have an OVF. These results suggest that sarcopenia may be a risk factor for OVF.

Does the Q - H index show a stronger relationship than the H:Q ratio in regard to knee pain during daily activities in patients with knee osteoarthritis?

[Purpose] The purpose of this study was to elucidate the relationship between knee muscle strength and knee pain in activities of daily living, based on consideration of the difference between extension and flexion strength (Q - H) and the hamstring:quadriceps (H:Q) ratio in patients with knee osteoarthritis. [Subjects and Methods] The participants were 78 females with knee osteoarthritis, and a total of 133 knees that had not been treated surgically were the targets of this research. The legs were divided according to dominance. Isometric knee extension and flexion muscle strength and knee pain during activities of daily living were measured. The H:Q ratio (flexion/extension muscle strength) and the difference between extension and flexion strength, (extension muscle strength/weight) minus (flexion muscle strength/weight), that is, Q - H, were calculated. The correlation between these indices and the knee pain score during activities of daily living was investigated. [Results] Greater knee pain during activities of daily living was related to lower knee extension muscle strength and Q - H in both the dominant and nondominant legs. Knee flexion muscle strength and the H:Q ratio were not significantly correlated with knee pain during any activities of daily living. [Conclusion] Knee extension muscle strength and Q - H were found to be significantly correlated with knee pain during activities of daily living, whereas the H:Q ratio was not.

Effects of a custom-made hinged knee brace with knee flexion support for patients with knee osteoarthritis:a preliminary study.

A knee brace for medial knee osteoarthritis (OA) is required to restrict knee adduction moment (KAM), but must not restrict knee flexion during swing phase. There is no report of a knee brace with both functions. The purpose of this study is to investigate the effect of the custom-made hinged knee brace for patients with knee OA compared to the hinged knee brace generally used, and to assess the KAM and knee flexion angle during swing phase. Fifteen patients (average age: 71.6 ± 7.8 years old) with medial knee OA participated. Gait analysis was performed using a 3-D motion analysis system to measure two conditions: hinged knee brace (KB), and a custom-made hinged knee brace with knee-flexion support- equipped rubber tubes at the posterior of the lateral and medial side poles (KBF). The peak KAM with KBF was significantly smaller than those with the KB (P=0.004, the difference between these conditions of KAM: 0.06 Nm/kg). The peak knee flexion angles during swing phase with KBF were also significantly larger than those with the KB (P=0.004, the difference between these conditions of knee flexion angle: 1.5 degrees). The custom-made brace with one type of tube actuator in the present study could decrease KAM and make for a small increase of knee flexion angle as opposed to the hinged knee brace.

Effects of knee extensor muscle strength on the incidence of osteopenia and osteoporosis after 6 years.

The association of knee extensor muscle strength with bone mineral density (BMD) has been reported in cross-sectional epidemiological studies, but it remains unclear whether or not this is the case with longitudinal change. Thus, we investigated whether or not the knee extension strength can predict the incidence of osteopenia or osteoporosis after 6 years, then compared the difference between sexes. Subjects were 1255 community-dwelling Japanese men and menopaused women, aged 40-81 years. BMD of lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry twice at 6-year intervals. Subjects were divided into three groups, normal, osteopenia, and osteoporosis, depending on their young adult mean BMD % value. In the cross-sectional analysis the correlations between the knee extension strength and BMD of the two regions were examined, using Pearson's correlation coefficient. Longitudinal analyses were then conducted to determine the odds ratio, controlled for age and BMI, given that those who were normal in the initial stage developed osteopenia or osteoporosis after 6 years, for every 1 SD decrease in knee extension strength, as well as those who first had normal or osteopenia and then developed osteoporosis. Cross-sectional analysis showed a statistically significant relation between knee extensor muscle strength and BMD at both the lumbar spine (p = 0.02) and the femoral neck (p < 0.0001) only in men. The longitudinal analysis showed the significant effect of muscle strength on the loss of femoral neck BMD from normal to osteopenia or osteoporosis both in men (OR 1.84, 95 % CI 1.36-2.48, p < 0.0001) and in women (OR 1.29, 95 % CI 1.002-1.65, p < 0.05), as well as on the loss of spinal BMD from normal or osteopenia to osteoporosis only in men (OR 2.97, 95 % CI 1.07-8.23, p < 0.05). The results suggest the importance of knee extension strength to maintain the bone health of the proximal femur and spine in aging particularly in men.

Concordance in oral frailty five-item checklist and oral hypofunction: Examining their respective characteristics.

OBJECTIVES: This study examined the diagnostic concordance and characteristics of the oral frailty five-item checklist (OF-5) and oral hypofunction (OHF). MATERIALS AND METHODS: In this extensive cross-sectional study, older adults were enrolled at a research hospital frailty clinic between July 2021 and July 2023. The diagnosis of OF-5 and OHF was conducted using the proposed assessment methods. The concordance rate of these criteria was determined by evaluating each patient and calculating the number of patients meeting each diagnosis's criteria. Patients who tested negative for the OF-5 and OHF criteria and those who met only one criterion were included in the OF-5 and OHF characteristic analysis. RESULTS: A total of 248 patients were included in the analysis (mean age 77.6 ± 6.8 years; 36.7 % men). Among the patients, 114 (46.0 %) and 116 (46.8 %) met the OF-5 and OHF criteria, respectively. Furthermore, 78 (31.5 %) participants met both the OF-5 and OHF criteria, whereas 96 (38.7 %) did not meet either criterion. Moreover, 36 (14.5 %) and 38 (15.3 %) patients tested exclusively positive for OF-5 and OHF, respectively. The OF-5-positive and OHF-negative group showed an older age, lower Mini Nutritional Assessment Short Form score, and higher fall risk than the OF-5-negative and OHF-negative group. However, no significant differences were observed between the OF-5-negative and OHF-positive and OF-5-negative and OHF-negative groups. CONCLUSION: The concordance rate of OF-5 and OHF diagnoses was 70.2 %. OF-5 showed a potential association with nutritional status and fall risk. Further longitudinal analyses are warranted to explore our study results.

Association between intrinsic capacity and oral health in older patients in a frailty clinic.

PURPOSE: This study aimed to investigate how intrinsic capacity (IC) deficit is associated with oral functional decline. METHODS: This cross-sectional study enrolled older adults at a research hospital frailty clinic between July 2021 and May 2023. IC evaluation included the locomotion, cognition, vitality, psychology, and sensory domains. Criteria for deficits were established within each domain, and the number of IC deficit domains was calculated for each patient. Oral function assessment included oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function. Patients who met three or more criteria were classified into the oral hypofunction (OHF) group. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between IC deficit and OHF. RESULTS: Of 222 included patients (mean age 78.3 ± 6.3 years; 39.6% men), 105 (47.3%) met the criteria for OHF. This OHF group showed a significantly higher prevalence of locomotion, cognition, psychology, and sensory domain deficits than the normal oral function group. Multivariate analysis adjusted for age and sex revealed a significant association between IC deficits and OHF (odds ratio [OR], 1.33; 95% confidence interval [CI] 1.04-1.70). A significant association was also observed between the locomotion domain and OHF (OR, 2.06; 95% CI 1.13-3.76). CONCLUSION: This study highlights the potential relationship between the number of IC domain deficits and oral functional decline, with the most significant domain being locomotion. Furthermore, it suggests a possible link between sensory and oral function.

Association between oral frailty and sarcopenia among frailty clinic outpatients: A cross-sectional study.

OBJECTIVES: In this study, we aimed to investigate the prevalence of oral frailty and explore its relationship with oral function and sarcopenia among older outpatients. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively included older patients who visited a frailty outpatient clinic. We assessed total oral frailty employing, among other measures, oral diadochokinesis (/ta/ sound) for tongue-lip movement and tongue pressure. Patients who did not meet the cut-off values for three or more of these were classified as having oral frailty. Sarcopenia was assessed according to Asian Working Group for Sarcopenia 2019 criteria and analyzed for the relationship with oral function. RESULTS: The mean ± standard deviation age of the 111 patients was 77.2 ± 5.7 y; 63 were women (57%). Fifteen patients (14%) had either sarcopenia or dynapenia. The overall prevalence of oral frailty was 38%, with no significant difference in its prevalence between the sarcopenia/dynapenia group (44%) and the robust (no sarcopenia/dynapenia) group (35%). The following oral function assessments significantly differed between the sarcopenia/dynapenia group and the robust group: median (interquartile range) total oral frailty score, 2 (2-4) and 2 (1-3) (P = 0.019); tongue-lip motor function, 5.4 ± 1.2 and 5.9 ± 1.2 times/s (P = 0.049); and tongue pressure, 27.3 ± 8.5 kPa and 31.7 ± 8.0 kPa (P = 0.009). CONCLUSIONS: Approximately 40% of patients exhibited a decline in oral function regardless of the presence of sarcopenia. Sarcopenia and dynapenia may particularly affect tongue function. Although assessing patients for sarcopenia is crucial, separate evaluations of oral function should also be considered.

Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle.

BACKGROUND: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. METHODS: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. RESULTS: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O+ area). In consistency with in-vitro findings, VdrMPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. CONCLUSIONS: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Longitudinal association between muscle and bone loss: Results of US and Japanese cohort studies.

BACKGROUND: Muscle and bone are physiologically interconnected, but joint changes of muscle and bone with aging, and whether the muscle-bone changes are different by sex and by country has been little studied. We examined longitudinal associations of bone mineral density (BMD) and muscle mass or muscle strength in community-dwelling 65 years or older in the United States and Japan. METHODS: The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5 ± 7.5 years; women, 49.8%) and 1998 women and men from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) (mean age, 70.0 ± 4.5 years; women, 51.4%). Median follow-up was 4.6 (min-max, 0-15.4) years in the BLSA and 4.0 (min-max, 0-13.4) years in the NILS-LSA. We selected visits at which participants had BMD (whole body, pelvic, femoral neck, trochanter, and Ward's triangle BMDs) and muscle mass [appendicular lean mass, (ALM)] measured by DXA scan. In each bone site, we ran cohort-specific bivariate linear mixed-effects models adjusted for baseline age, sex, body height, body weight, fat mass, education year, and smoking status. Race was an additional adjustment in the BLSA. Additionally, we performed sex-specific analyses. RESULTS: In the BLSA, the rate of change in ALM positively correlated with the rate of change in the whole body (rho = 0.30, P < 0.0001) and pelvic BMD (rho = 0.24, P < 0.0001), but not in trochanter, femoral neck, or Ward's triangle BMD (P > 0.05). In the NILS-LSA, ALM positively correlated with the rate of change in all bone sites (rho ranged from 0.20 to 0.71, P < 0.01). In women, ALM positively correlated with the rate of change in all bone sites in both cohorts (in the NILS-LSA, rho ranged from 0.35 to 0.91, P < 0.01; in the BLSA, rho ranged from 0.26 to 0.56, P < 0.05) except for femoral neck BMD in the BLSA. In men, ALM positively correlated with pelvic, trochanter, and Ward's triangle BMD in the NILS-LSA (rho ranged from 0.45 to 0.68, P < 0.0001), and whole body and trochanter BMD in the BLSA (both, rho = 0.20, P < 0.05). CONCLUSIONS: Muscle loss co-occurred with bone loss in both cohorts, but the association in the NILS-LSA tended to be stronger than in the BLSA, and the association was higher in women than in men, implying that the association may differ by sex and country.