Ageing Research Reviews, volume 73, pages 101530

Biomarkers shared by frailty and sarcopenia in older adults: A systematic review and meta-analysis

Anna Picca 1, 2
, 
Hélio J. Coelho-Junior 3
, 
Riccardo Calvani 4, 5
, 
Emanuele Marzetti 6, 7
, 
Davide Liborio Vetrano 1, 2
1
 
2
 
3
 
4
 
5
 
6
 
7
 
Publication type: Journal Article
Publication date: 2022-01-01
scimago Q1
SJR: 3.376
CiteScore: 19.8
Impact factor: 12.5
ISSN: 15681637, 18729649
Biochemistry
Molecular Biology
Biotechnology
Neurology
Aging
Abstract
Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear.We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and random-effect models. Sensitivity analysis was performed based on age and the setting where the study was conducted.Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60-88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68-87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had higher levels of tumor necrosis factor alpha compared with their robust and non-sarcopenic counterparts.A set of metabolic, hematologic, and inflammatory biomarkers was found to be shared by frailty and sarcopenia. These findings fill a knowledge gap in the quest of biomarkers for these conditions and provide a rationale for biomarker selection in studies on frailty and sarcopenia.
Found 139
By date By citations
Springer Nature
Dual effects of insulin resistance on mortality and function in non-diabetic older adults: findings from the Toledo Study of Healthy Aging
Rodríguez-Mañas L., Angulo J., Carnicero J.A., El Assar M., García-García F.J., Sinclair A.J.
GeroScience scimago Q1 wos Q1 , 
2021-06-01,  citations by CoLab: 23 ,  Abstract  
Insulin signalling declines with increasing age and impacts skeletal muscle function and longevity in animal models. Our aim was to assess the relationships between insulin resistance (IR) and frailty and mortality in a unique community-dwelling cohort of older people. 991 non-diabetic subjects from the Toledo Study of Healthy Ageing (TSHA) cohort were included. IR was estimated by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was determined by frailty phenotype (FP) and Frailty Trait Scale (FTS) at baseline and after 5-year follow-up. Deaths were also determined. Multivariate regression models were used to analyze the effects of HOMA-IR on outcomes. Age, gender, BMI, education level, cardio- and cerebro-vascular disease, glomerular filtration rate, and disability were included as potential confounding variables in progressive adjustment models. IR determined as increasing log HOMA-IR was inversely associated with risk of mortality. The association remained significant for all adjustment models (HR: 0.64–0.69). When we analyzed survival curves, the higher the HOMA-IR tertile, the lower the mortality rate (highest vs lowest tertile, p = 0.0082). In contrast, IR increased the risk of incident frailty determined by FP (OR 1.81 [1.14–2.87]) as well as deterioration of frailty status determined by worsening in FTS score (OR 1.28 [1.01–1.63]) at 5-year follow-up. In non-diabetic older subjects, IR significantly increases the risk for frailty and functional decline but decreased the risk of death at 5-year follow-up. This finding raises the need of assessing the effect of biomarkers on different outcomes before establishing their role as biomarkers of aging.
Public Library of Science (PLoS)
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., Chou R., Glanville J., Grimshaw J.M., Hróbjartsson A., Lalu M.M., et. al.
PLoS Medicine scimago Q1 wos Q1 Open Access , 
2021-03-29,  citations by CoLab: 5653 ,  PDF, 
MDPI
Biological Rhythm and Chronotype: New Perspectives in Health
Montaruli A., Castelli L., Mulè A., Scurati R., Esposito F., Galasso L., Roveda E.
Biomolecules scimago Q1 wos Q1 Open Access , 
2021-03-24,  citations by CoLab: 167 ,  PDF,  Abstract  
The circadian rhythm plays a fundamental role in regulating biological functions, including sleep–wake preference, body temperature, hormonal secretion, food intake, and cognitive and physical performance. Alterations in circadian rhythm can lead to chronic disease and impaired sleep. The circadian rhythmicity in human beings is represented by a complex phenotype. Indeed, over a 24-h period, a person’s preferred time to be more active or to sleep can be expressed in the concept of morningness–eveningness. Three chronotypes are distinguished: Morning, Neither, and Evening-types. Interindividual differences in chronotypes need to be considered to reduce the negative effects of circadian disruptions on health. In the present review, we examine the bi-directional influences of the rest–activity circadian rhythm and sleep–wake cycle in chronic pathologies and disorders. We analyze the concept and the main characteristics of the three chronotypes.
MDPI
Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms
Nani A., Murtaza B., Sayed Khan A., Khan N.A., Hichami A.
Molecules scimago Q1 wos Q2 Open Access , 
2021-02-12,  citations by CoLab: 185 ,  PDF,  Abstract  
Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.
Springer Nature
Effects of resistance training on muscle strength, insulin-like growth factor-1, and insulin-like growth factor–binding protein-3 in healthy elderly subjects: a systematic review and meta-analysis of randomized controlled trials
Amiri N., Fathei M., Mosaferi Ziaaldini M.
Hormones scimago Q2 wos Q3 , 
2021-01-13,  citations by CoLab: 16 ,  Abstract  
Findings regarding the effects of resistance training (RT) on muscle strength, serum level of IGF-1, and its binding proteins are contradictory. To resolve this contradiction, we performed a systematic review and meta-analysis to investigate the effects of RT on muscle strength, the levels of serum IGF-1, and IGF-binding protein-3 in the elderly and aged. The PubMed, CINAHL, Medline, Google Scholar, and Scopus databases and reference lists of included studies were systematically searched to identify randomized controlled trials (RCTs) comparing subjects who underwent RT and control individuals up to May 15, 2020. This study was performed following the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses guidelines. We identified and analyzed 11 eligible trials in this meta-analysis. Pooled data displayed an overall significant elevation in IGF-1 (mean difference (MD): 17.34 ng/ml; 95% confidence interval (CI): 7.23, 27.46) and in muscle strength in leg press (SMD: 0.82; 95% CI: 0.30, 1.34) and bench press (SMD: 0.82; 95% CI: 0.42, 1.23) following RT. By contrast, the pooled estimate showed a non-significant elevation in IGFBP-3 (MD: 0.13 ng/ml; 95% CI: − 39.39, 39.65). Subgroup analysis revealed that the elevation in serum IGF-1 levels after RT was significant only in women (MD: 19.30 ng/ml); moreover, it increased after intervention durations of both > 12 weeks (MD: 21.98 ng/ml) and of ≤ 12 weeks (MD: 15.31 ng/ml). RT was associated with elevated muscle strength. Moreover, RT was correlated with increased serum levels of IGF-1 among women and among those who received the training for ≤ 12 weeks or > 12 weeks. Further studies are required to elucidate the mechanisms underlying the impact of RT on IGF-1, IGFBP-3, and muscle strength.
Elsevier
Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis
Tuttle C.S., Thang L.A., Maier A.B.
Ageing Research Reviews scimago Q1 wos Q1 , 
2020-12-01,  citations by CoLab: 368 ,  Abstract  
Chronic inflammation has been associated with sarcopenia and its components skeletal muscle strength and muscle mass. The aim of this systematic review and meta-analysis was to determine the relationship between systemic inflammation, muscle strength and/or muscle mass in adults.An electronic search using keywords such as 'acute phase proteins, cytokines and sarcopenia, muscle mass, muscle strength' was conducted via Pubmed, Web of Science and Embase from inception until the 30th of June 2020. A meta-analysis using correlation data was performed to determine the overall relationship between inflammation and muscle strength and muscle mass in adults.Overall, 168 articles; 149 cross-sectional articles (n = 76,899 participants, 47.0 % male) and 19 longitudinal articles (n = 12,295 participants, 31.9 % male) met inclusion criteria. Independent of disease state, higher levels of C reactive protein (CRP), Interleukin (IL)-6 and Tumor necrosis factor (TNF)α were associated with lower handgrip and knee extension strength (CRP; r = -0.10, p < 0.001, IL-6; r = -0.13, p < 0.001, TNFα; r = -0.08, p < 0.001 and CRP; r = -0.18, p < 0.001, IL-6; r = -0.11, p < 0.001, TNFα; r = -0.13, p < 0.001 respectively) and muscle mass (CRP; r = -0.12, p < 0.001, IL-6; r = -0.09, p < 0.001, TNFα; r = -0.15, p < 0.001). Furthermore, higher levels of systemic inflammatory markers appeared to be associated with lower muscle strength and muscle mass over time.Higher levels of circulating inflammatory markers are significantly associated with lower skeletal muscle strength and muscle mass.
Springer Nature
Association between telomere length, frailty and death in older adults
El Assar M., Angulo J., Carnicero J.A., Walter S., García-García F.J., Rodríguez-Artalejo F., Rodríguez-Mañas L.
GeroScience scimago Q1 wos Q1 , 
2020-11-15,  citations by CoLab: 12 ,  Abstract  
Frailty is considered a clinical marker of functional ageing. Telomere length (TL) has been proposed as a biomarker of biological age but its role in human ageing is controversial. The main aim of the study was to evaluate the longitudinal association of TL with incident frailty and mortality in two cohorts of Spanish community–dwelling older adults. TL was determined at baseline in blood samples from older adults included in Toledo Study for Healthy Aging and ENRICA cohorts while frailty was determined by frailty phenotype (FP) at baseline and at follow-up (3.5 years). Deaths occurring during follow-up were also recorded. Associations of TL with frailty and mortality were analysed by logistic regression with progressive adjustment. Data were separately analysed in the two cohorts and in all subjects by performing a meta-analysis. TL was not different between frail and non-frail subjects. Longer telomeres were not associated with lower risk of prevalent frailty. Similarly, TL at baseline failed to predict incident frailty (OR: 1.04 [0.88–1.23]) or even the development of a new FP criterion (OR: 0.97 [0.90–1.05]) at follow-up. Lack of association was also observed when analysing the development of specific FP criteria. Finally, while frailty at baseline was significantly associated with higher risk of death at follow-up (OR: 4.08 [1.97–8.43], p < 0.001), TL did not significantly change the mortality risk (OR: 1.05 [0.94–1.16]). Results show that TL does not predict incident frailty or mortality in older adults. This suggests that TL is not a reliable biomarker of functional age.
MDPI
Low Serum Branched-chain Amino Acid and Insulin-Like Growth Factor-1 Levels Are Associated with Sarcopenia and Slow Gait Speed in Patients with Liver Cirrhosis
Saeki C., Kanai T., Nakano M., Oikawa T., Torisu Y., Saruta M., Tsubota A.
Journal of Clinical Medicine scimago Q1 wos Q1 Open Access , 
2020-10-10,  citations by CoLab: 18 ,  PDF,  Abstract  
Branched-chain amino acid (BCAA) and insulin-like growth factor 1 (IGF-1) are essential for muscle protein synthesis. We investigated the association of serum BCAA and IGF-1 levels with sarcopenia and gait speed in 192 patients with liver cirrhosis (LC). Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. Slow gait speed was defined as <1.0 m/s. Subjects were divided into three groups based on baseline BCAA or IGF-1 levels: low (L), intermediate (I), and high (H) groups. The L-BCAA group had the highest prevalence of sarcopenia (60.4%, p < 0.001) and slow gait speed (56.3%, p = 0.008), whereas the H-BCAA group had the lowest prevalence of sarcopenia (8.5%, p < 0.001). The L-IGF-1 group showed the highest prevalence of sarcopenia (46.9%, p < 0.001), whereas the H-IGF-1 group had the lowest prevalence of sarcopenia (10.0%, p < 0.001) and slow gait speed (18.0%, p = 0.003). Using the optimal BCAA and IGF-1 cutoff values for predicting sarcopenia (372 μmol/L and 48.5 ng/mL, respectively), the sensitivity and specificity were 0.709 and 0.759 for BCAA and 0.636 and 0.715 for IGF-1, respectively. Low serum BCAA and IGF-1 levels were associated with sarcopenia and slow gait speed in patients with LC.
MDPI
Protein Intake and Frailty: A Matter of Quantity, Quality, and Timing
Coelho-Junior H.J., Marzetti E., Picca A., Cesari M., Uchida M.C., Calvani R.
Nutrients scimago Q1 wos Q1 Open Access , 
2020-09-23,  citations by CoLab: 96 ,  PDF,  Abstract  
Frailty is a geriatric syndrome that refers to a state of reduced resiliency to stressful events that occurs in response to physiological and/or psychosocial detriments. Frailty is a predictor of poor prognosis, given that frail older adults are at higher risk of many adverse health-related events. Hence, the identification of potential strategies to prevent the development and progression of frailty is of extreme importance for avoiding its negative outcomes. An adequate protein consumption is advocated as a possible intervention for the management of frailty in older adults due to its effects on muscle mass and physical function. However, empirical evidence is still needed to support this proposition. On the other hand, substantial evidence from observational studies has provided important information on the association between frailty and dietary protein-related parameters. Here, we provide a narrative review of the current literature regarding the association between protein intake (amount (how much?), quality (what type?), and distribution across meals (when?)) and frailty-related parameters. The ultimate aim of this work is to offer practical, evidence-based indications to healthcare professionals responsible for the care of frail older adults.
Frontiers Media S.A.
Circulating Mitochondrial-Derived Vesicles, Inflammatory Biomarkers and Amino Acids in Older Adults With Physical Frailty and Sarcopenia: A Preliminary BIOSPHERE Multi-Marker Study Using Sequential and Orthogonalized Covariance Selection – Linear Discriminant Analysis
Marzetti E., Guerra F., Calvani R., Marini F., Biancolillo A., Gervasoni J., Primiano A., Coelho-Júnior H.J., Landi F., Bernabei R., Bucci C., Picca A.
Frontiers in Cell and Developmental Biology scimago Q1 wos Q1 Open Access , 
2020-09-22,  citations by CoLab: 37 ,  PDF,  Abstract  
Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The multifaceted pathophysiology of this condition recapitulates all hallmarks of aging making the identification of specific biomarkers challenging. In the present study, we explored the relationship among three processes that are thought to be involved in PF&S (i.e, systemic inflammation, amino acid dysmetabolism, and mitochondrial dysfunction). We took advantage of the well-characterized cohort of older adults recruited in the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study to preliminarily combine in a multi-platform analytical approach inflammatory biomolecules, amino acids and derivatives, and mitochondrial-derived vesicle (MDV) cargo molecules to evaluate their performance as possible biomarkers for PF&S. Eleven older adults aged 70 years and older with PF&S and 10 non-sarcopenic non-frail controls were included in the analysis based on the availability of the three categories of biomolecules. A sequential and orthogonalized covariance selection − linear discriminant analysis (SO-CovSel−LDA) approach was used for biomarkers selection. Of the 75 analytes assayed, 16 had concentrations below the detection limit. Within the remaining 59 biomolecules, So-CovSel−LDA selected a set comprising two amino acids (phosphoethanolamine and tryptophan), two cytokines (interleukin 1 receptor antagonist and macrophage inflammatory protein 1β), and MDV-derived nicotinamide adenine dinucleotide reduced form:ubiquinone oxidoreductase subunit S3 as the best predictors for discriminating older people with and without PF&S. The evaluation of these biomarkers in larger cohorts and their changes over time or in response to interventions may unveil specific pathogenetic pathways of PF&S and identify new biological targets for drug development.
MDPI
Impact of Galectin-3 Circulating Levels on Frailty in Elderly Patients with Systolic Heart Failure
Komici K., Gnemmi I., Bencivenga L., Vitale D.F., Rengo G., Di Stefano A., Eleuteri E.
Journal of Clinical Medicine scimago Q1 wos Q1 Open Access , 
2020-07-14,  citations by CoLab: 20 ,  PDF,  Abstract  
Background: Heart Failure (HF), a leading cause of morbidity and mortality, represents a relevant trigger for the development of frailty in the elderly. Inflammation has been reported to play an important role in HF and frailty pathophysiology. Galectin-3 (Gal-3), whose levels increase with aging, exerts a relevant activity in the processes of cardiac inflammation and fibrosis. The aim of the present study was to investigate the potential of Galectin-3 to serve as a biomarker of frailty in HF patients. Methods: 128 consecutive patients aged 65 and older with the diagnosis of systolic HF underwent a frailty assessment and blood sample collection for serum Gal-3 detection. A multivariable regression analysis and decision curve analysis (DCA) were used to identify significant predictors of frailty. Results: Frailty was present in 42.2% of patients. Age: Odds Ratio (OR) = 3.29; 95% Confidence Interval CI (CI) = 1.03–10.55, Cumulative Illness Rating Scale Comorbidity Index (CIRS-CI): OR = 1.85; 95% CI = 1.03–3.32, C-Reactive phase Protein (CRP) OR = 3.73; 95% CI = 1.24–11.22, N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP): OR = 2.39; 95% CI = 1.21–4.72 and Gal-3: OR = 5.64; 95% CI = 1.97–16.22 resulted in being significantly and independently associated with frailty. The DCA demonstrated that the addition of Gal-3 in the prognostic model resulted in an improved clinical ‘net’ benefit. Conclusions: Circulating levels of Gal-3 are independently associated with frailty in elderly patients with systolic HF.
Springer Nature
Low serum albumin, aspartate aminotransferase, and body mass are risk factors for frailty in elderly people with diabetes–a cross-sectional study
Yanagita I., Fujihara Y., Iwaya C., Kitajima Y., Tajima M., Honda M., Teruya Y., Asakawa H., Ito T., Eda T., Yamaguchi N., Kayashima Y., Yoshimoto M., Harada M., Yoshimoto S., et. al.
BMC Geriatrics scimago Q1 wos Q2 Open Access , 
2020-06-09,  citations by CoLab: 31 ,  PDF,  Abstract  
Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones. We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n = 148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis. Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS < 70 μg/dL and cortisol/DHEA-S ratio ≥ 0.2. Multiple regression analysis showed that low albumin (< 4.0 g/dl) (odds ratio [OR] = 5.79, p < 0.001), low aspartate aminotransferase (AST) activity (< 25 IU/L) (OR = 4.34, p = 0.009), and low body mass (BM) (< 53 kg) (OR = 3.85, p = 0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM. Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients.
Springer Nature
Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: results from the BIOSPHERE study
Calvani R., Picca A., Marini F., Biancolillo A., Gervasoni J., Persichilli S., Primiano A., Coelho-Junior H.J., Cesari M., Bossola M., Urbani A., Onder G., Landi F., Bernabei R., Marzetti E.
GeroScience scimago Q1 wos Q1 , 
2020-06-01,  citations by CoLab: 54 ,  Abstract  
Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a “core” biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1β, with peculiar signatures in men and women. SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.
Elsevier
A potential urinary biomarker to determine frailty status among older adults
Jiang S., Kang L., Zhu M., Zhang X., Wang C., Cai J., Liu X.
Archives of Gerontology and Geriatrics scimago Q1 wos Q2 , 
2020-05-01,  citations by CoLab: 9 ,  Abstract  
Association of oxidative stress biomarkers with aging and several age-related diseases is well documented. However, the possible role of these factors on frailty status in older adults has not been extensively studied.To evaluate whether urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), a biomarker of RNA oxidative damage, was independently associated with frailty.In this cross-sectional analysis, frailty phenotype was assessed among 230 participants living in a senior community. Participants received a comprehensive geriatric assessment. Serum high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, and 8-oxo-Gsn were measured.Participants' mean age was 83.9 ± 4.4 years. In total, 33 % were frail, 45 % were pre-frail, and 22 % were non-frail. Urinary 8-oxo-Gsn, serum hsCRP, and WBC were significantly higher in the frail group than in the non-frail and pre-frail groups (p-values < 0.05). Adjusting for age, sex, and Charlson comorbidity index, statistically significant positive associations with frailty were observed for urinary 8-oxo-Gsn (odds ratio [OR]: 1.70, 95 % confidence interval [CI]: 0.264-0.732) and hsCRP (OR: 1.337, 95 % CI: 0.089-0.412). Urinary 8-oxo-Gsn of 3.175 μmol/mol had the optimal predictive value for frailty, with an area under the receiver operating characteristic curve (AUC) of 0.72 (95 % CI: 0.649-0.788). The prediction probability combining urinary 8-oxo-Gsn and a simple question evaluating exhaustion had the optimal predictive value for frailty, with an AUC of 0.90 (p < 0.001, 95 % CI: 0.85-0.95).Urinary 8-oxo-Gsn level was independently associated with frailty. This urinary biomarker may be a promising indicator of frailty.
Elsevier
Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of frailty for elderly patients with cardiovascular disease
Liang Y., Liu Q., Du M., Liu Z., Yao S., Zheng P., Wan Y., Sun N., Li Y., Liu J., Luo Y., Cai J., Yang J., Wang H.
Free Radical Biology and Medicine scimago Q1 wos Q1 , 
2020-05-01,  citations by CoLab: 13 ,  Abstract  
The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1–2 scores; frail: 3–5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P  Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future.
Found 192
By date By citations
Elsevier
Long-term prognostic value of CRP–albumin–lymphocyte index in elderly patients with heart failure with preserved ejection fraction
He Q., Cao Y., Fan X., Li B., He Q., Zhang H.
Experimental Gerontology scimago Q1 wos Q2 Open Access , 
2025-06-01,  citations by CoLab: 0 , 
Elsevier
Association of nutritional and inflammatory status with all-cause and cardiovascular mortality in adults with sarcopenia: Insights from NHANES
Yang Y., Shen S., Luo X., Liu Y., Wang Z., Li Y., Zhang X., Zhang Z.
Maturitas scimago Q1 wos Q1 , 
2025-05-01,  citations by CoLab: 0 , 
Springer Nature
The effect of sarcopenia on prognosis in patients with mild acute ischemic stroke: a prospective cohort study
Chen R., Liu Z., Liao R., Liang H., Hu C., Zhang X., Chen J., Xiao H., Ye J., Guo J., Wei L.
BMC Neurology scimago Q2 wos Q3 Open Access , 
2025-03-27,  citations by CoLab: 0 ,  PDF, 
Wiley
Nanoparticle‐Driven Skeletal Muscle Repair and Regeneration Through Macrophage‐Muscle Stem Cell Interaction
Xu L., Zhang Y., Wang D., Ren Q., Wang Y., Zang Z., Guo A., Guo J., Wang L., Wang R., Liu Y.
Small scimago Q1 wos Q1 , 
2025-03-20,  citations by CoLab: 0 ,  Abstract  
AbstractMacrophages are key innate immune cells in the muscle environment of sarcopenia patients, significantly influencing muscle stem cell (MuSC) proliferation and differentiation. However, prolonged activation of macrophages can hinder muscle recovery. In this study, it synthesizes lipoic acid‐modified gold nanoparticles (LA‐Au NPs) of varying sizes to evaluate their biocompatibility and immunomodulatory effects. The findings demonstrate that LA‐Au NPs exhibit excellent biocompatibility with macrophages and promoted M2 polarization in a size‐dependent manner. Mechanistically, LA‐Au NPs facilitated metabolic reprogramming in macrophages by enhancing lysosomal autophagy and mitochondrial oxidative phosphorylation. Furthermore, macrophages are shown to chemotax toward MuSCs, regulating their proliferation via the chemokine system, inhibiting MuSC apoptosis, and enhancing differentiation under inflammatory conditions. In vivo studies have confirmed the safety and efficacy of LA‐Au NPs in sarcopenia mice. To further enhance the effectiveness of LA‐Au NPs, it investigates a delivery strategy that involves preconditioning macrophages with LA‐Au NPs (Mac@Au NPs). Compared to the direct injection of LA‐Au NPs, Mac@Au NPs demonstrate significantly greater benefits for muscle repair. This highlights the potential of macrophage therapy as a promising strategy for effective muscle regeneration and therapeutic intervention in sarcopenia.
American Association for the Advancement of Science (AAAS)
Biological age prediction using a DNN model based on pathways of steroidogenesis
Wang Q., Wang Z., Mizuguchi K., Takao T.
Science advances scimago Q1 wos Q1 Open Access , 
2025-03-14,  citations by CoLab: 0 ,  PDF,  Abstract  
Aging involves the progressive accumulation of cellular damage, leading to systemic decline and age-related diseases. Despite advances in medicine, accurately predicting biological age (BA) remains challenging due to the complexity of aging processes and the limitations of current models. This study introduces a method for predicting BA using a deep neural network (DNN) based on pathways of steroidogenesis. We analyzed 22 steroids from 148 serum samples of individuals aged 20 to 73, using 98 samples for model training and 50 for validation. Our model reflects the often-overlooked fact that aging heterogeneity expands over time and uncovers sex-specific variations in steroidogenesis. This study leveraged key markers, including cortisol (COL), which underscore the role of stress-related and sex-specific steroids in aging. The resulting model establishes a biologically meaningful and robust framework for predicting BA across diverse datasets, offering fresh insights and supporting more targeted strategies in aging research and disease management.
Elsevier
Cross-sectional associations between clinical biochemistry and nutritional biomarkers and sarcopenic indices of skeletal muscle in the Baltimore Longitudinal Study of Aging.
Scott J., Yates M., Tanaka T., Ferrucci L., Cameron D., Welch A.A.
Journal of Nutrition scimago Q1 wos Q2 , 
2025-03-08,  citations by CoLab: 0 , 
MDPI
Frailty in Geriatrics: A Critical Review with Content Analysis of Instruments, Overlapping Constructs, and Challenges in Diagnosis and Prognostic Precision
Fierro-Marrero J., Reina-Varona Á., Paris-Alemany A., La Touche R.
Journal of Clinical Medicine scimago Q1 wos Q1 Open Access , 
2025-03-07,  citations by CoLab: 0 ,  PDF,  Abstract  
Frailty is a key concept in geriatric care; yet its definition and assessment remain debated. Since the early 2000s, two main models have emerged: the Fried frailty phenotype, focusing on physical deficits, and the Mitnitski frailty index, which incorporates broader health factors. These divergent approaches have led to over 50 frailty instruments, reflecting the absence of a unified framework. This review explores the content, weighting, and scoring methods of frailty instruments, identifying potential concerns derived from this. This review exposes the overlap of frailty with other constructs including function, disability, morbidity, and sarcopenia. Many instruments lack content validity, and detect highly heterogeneous samples within and between scales, all labeled under the “frail” tag. This poses challenges to interpreting instrument responsiveness. In addition, frailty should not be considered a clinical entity with a unique etiology. This review discusses how the broad nature of frailty conflicts with modern paradigms of individualization and precision. They may be useful in primary care, but lack the specificity for secondary care evaluations. This article also discusses how the predictive validity of frailty should be interpreted with caution. Finally, we summarize our findings and propose a new definition of frailty, highlighting the strengths and weaknesses of the construct. The identified inconsistencies should serve as a guide for refining the concept of frailty, both in research and in its application to geriatric care.
Wiley
Genetic evidence for the effects of glucokinase activation on frailty‐related outcomes: A Mendelian randomisation study
Hua R., Shi M., Chow E., Yang A., Cheung Y.T.
Diabetes, Obesity and Metabolism scimago Q1 wos Q1 , 
2025-03-04,  citations by CoLab: 0 ,  Abstract  
AbstractAimsWe aimed to use the Mendelian randomisation (MR) design to investigate the potential causal effects of glucokinase (GK) activation on frailty‐related outcomes and to explore the potential mediating effects of metabolic and inflammatory biomarkers.Materials and MethodsSeventeen independent single‐nucleotide polymorphisms (SNPs) located within the GCK gene and significantly correlated with the glycated haemoglobin (HbA1c) level were used as genetic proxies for the effect of GK activation. We employed two‐sample MR analysis to assess the relationship between genetically proxied GK activation and multifactorial frailty‐related outcomes (frailty index, grip strength, walking pace, appendicular lean mass [ALM] and telomere length) We also explored the potential mediating effects using two‐step MR.ResultsGenetically proxied GK activation was significantly associated with a lower frailty index (beta: −0.161 per 1% decrease in HbA1c level due to GK activation, 95% confidence interval: −0.282 to −0.040, false discovery rate‐adjusted p = 0.011). Additionally, GK activation showed significant associations with increased grip strength, higher ALM, faster walking pace and longer telomere length. GK activation also demonstrated a significant indirect effect on total grip strength and telomere length by reducing C‐reactive protein levels (proportion of mediation: 6.79% to 8.21%).ConclusionOur study provides genetic evidence supporting the causal effects of GK activation on lowering the risk of frailty. These findings suggest that GK activators (GKAs) may aid in the management of frailty and sarcopaenia in people with diabetes; however, future randomized controlled trials are necessary to validate these results and establish their clinical applicability.
Taylor & Francis
The Biological Rationale for Integrating Intrinsic Capacity Into Frailty Models
Yu Z., Lozupone M., Chen J., Bao Z., Ruan Q., Panza F.
Clinical Interventions in Aging scimago Q1 wos Q2 Open Access , 
2025-03-04,  citations by CoLab: 0 ,  PDF, 
Springer Nature
Albumin/fibrinogen ratio (AFR): a significant predictor of postoperative delirium in older patients undergoing non-neurosurgical and non-cardiac surgery
Huo J., Song Y., Lu J., Dou G., Chen H., Mi W., Yu Y., Liu Y.
BMC Geriatrics scimago Q1 wos Q2 Open Access , 
2025-03-03,  citations by CoLab: 0 ,  PDF, 
MDPI
Translation and Validation of the Chinese Version of the Rapid Geriatric Assessment (C-RGA): A Screening Tool for Geriatric Syndromes in Nursing Home Residents
Liu J., Ismail A.H., Ibrahim R., Zhu Y., Hassan N.H.
Nutrients scimago Q1 wos Q1 Open Access , 
2025-02-28,  citations by CoLab: 0 ,  PDF,  Abstract  
Background: Frailty, sarcopenia, nutritional risk, and cognitive impairment are prevalent geriatric syndromes that adversely affect health outcomes in older adults, underscoring the need for an effective screen tool to enable early detection and timely intervention. Methods: This study employed a cross-sectional validation design and translated, culturally adapted, and validated the Chinese version of the Rapid Geriatric Assessment (C-RGA) among 416 nursing home residents. The C-RGA consists of four subscales: the simple frail questionnaire screening tool (FRAIL), SARC-F for sarcopenia (SARC-F), the Simplified Nutritional Assessment Questionnaire (SNAQ), and the Rapid Cognitive Screen (RCS). Results: The C-RGA demonstrated high content validity (S-CVI/Ave = 0.982) and strong internal consistency (Cronbach’s α = 0.839). Factor analysis confirmed its four-domain structure, accounting for 61.497% of the variance. Model fit indices demonstrated good construct validity (χ2/df = 1.122, RMSEA = 0.024, GFI, AGFI, and CFI > 0.90), supporting the robustness of the assessment tool. Pearson correlation analysis revealed a strong association between FRAIL and SARC-F with SNAQ (r = −0.671, 95% CI: [−0.742, −0.600], p < 0.01) and a moderate correlation with RCS (r = −0.426, 95% CI: [−0.513, −0.339], p < 0.01), underscoring the interplay among nutritional deficits, muscle weakness, and cognitive impairment. Conclusions: The C-RGA demonstrates strong psychometric properties, supporting its potential use as a screening tool for the early detection of frailty, sarcopenia, nutritional risk, and cognitive impairment among nursing home residents, enabling timely and targeted interventions. Future research should further assess its applicability across diverse healthcare settings to enhance its generalizability and clinical utility.
Springer Nature
The systemic inflammation response index as risks factor for all-cause and cardiovascular mortality among individuals with respiratory sarcopenia
Liu Y., Yin X., Guo Y., Xu J., Shao R., Kong Y.
BMC Pulmonary Medicine scimago Q2 wos Q2 Open Access , 
2025-02-26,  citations by CoLab: 0 ,  PDF, 
MDPI
Atrophic C2C12 Myotubes Activate Inflammatory Response of Macrophages In Vitro
Wu C., Tong Y., Huang J., Wang S., Kobori H., Zhang Z., Suzuki K.
Cells scimago Q1 wos Q2 Open Access , 
2025-02-20,  citations by CoLab: 0 ,  PDF,  Abstract  
Background: Skeletal muscle wasting is commonly observed in aging, immobility, and chronic diseases. In pathological conditions, the impairment of skeletal muscle and immune system often occurs simultaneously. Recent studies have highlighted the initiative role of skeletal muscle in interactions with immune cells. However, the impact of skeletal muscle wasting on macrophage inflammatory responses remains poorly understood. Methods: To investigate the effect of atrophic myotubes on the inflammatory response of macrophages, we established two in vitro models to induce myotube atrophy: one induced by D-galactose and the other by starvation. Conditioned medium (CM) from normal and atrophic myotubes were collected and administered to bone marrow-derived macrophages (BMDMs) from mice. Subsequently, lipopolysaccharide (LPS) stimulation was applied, and the expression of inflammatory cytokines was measured via RT-qPCR. Results: Both D-galactose and starvation treatments reduced myotube diameter and upregulated muscle atrophy-related gene expression. CM from both atrophic myotubes models augmented the gene expression of pro-inflammatory factors in BMDMs following LPS stimulation, including Il6, Il1b, and Nfkb1. Notably, CM from starvation-induced atrophic myotubes also enhanced Il12b, Tnf, and Nos2 expression in BMDMs after stimulation, a response not observed in D-galactose-induced atrophic myotubes. Conclusions: These findings suggest that CM from atrophic myotubes enhanced the expression of LPS-induced pro-inflammatory mediators in macrophages.
Springer Nature
Construction and validation of a risk prediction model for postoperative frailty in older adults:a multicenter study
Lu S., Liang H., Fang J., Chen R., Liao H., Xu M., Chen Y., Sun H., Dong L., Guo Y., Jiang Z., Xiao H., Wei L.
BMC Geriatrics scimago Q1 wos Q2 Open Access , 
2025-02-10,  citations by CoLab: 0 ,  PDF,  Abstract  
Postoperative frailty is an important determinant of postoperative recovery and survival outcomes. Predicting the onset of postoperative frailty is significant importance for the rehabilitation of the elderly people after surgery. Our study aims to develop and evaluate a predictive model for postoperative frailty on the 30th day in elderly patients. Data from seven Guangzhou hospitals were collected, encompassing 2,290 patients for analysis. This study constructed the model using LASSO regression and stepwise regression, and the optimal predictive model was selected based on comparison. Model performance was assessed through calibration curves, the area under the ROC curve (AUC), and decision curve analysis (DCA). The final model included the following variables: American Society of Anesthesiologists (ASA) grade, intraoperative blood loss, economic income, caregiver status, sedentary behavior, cognitive function, Activities of Daily Living (ADL), postoperative hemoglobin (Hb) level, and postoperative ICU admission. The model demonstrated good discrimination, with an area under the curve (AUC) of 0.7431 (95% CI = 0.7073–0.7788) in the training set and 0.7285 (95% CI = 0.6671–0.7624) in the validation set. According to general demographic information, lifestyle habits, and surgery-related factors, a predictive model for postoperative frailty in the elderly was constructed, which has good predictive power. This model can identify high-risk populations for postoperative frailty and provides a reference for the early detection and intervention of frailty in the elderly in clinical practice. This study was registered on May 17, 2023, at the Chinese Clinical Trial Registry (registration number: ChiCTR2300071535).
Taylor & Francis
Bidirectional causal associations between frailty measures and sleep disturbances: a two-sample Mendelian randomization study
Che L., Zang H., Bi Y., Wen B., Xu L.
Nature and Science of Sleep scimago Q2 wos Q2 Open Access , 
2025-02-07,  citations by CoLab: 0 ,  PDF, 

Top-30

Journals

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BMC Geriatrics
BMC Geriatrics, 13, 6.88%
Experimental Gerontology
Experimental Gerontology, 9, 4.76%
Ageing Research Reviews
Ageing Research Reviews, 8, 4.23%
Frontiers in Public Health
Frontiers in Public Health, 7, 3.7%
Nutrients
Nutrients, 7, 3.7%
Frontiers in Endocrinology
Frontiers in Endocrinology, 4, 2.12%
International Journal of Molecular Sciences
International Journal of Molecular Sciences, 4, 2.12%
Archives of Gerontology and Geriatrics
Archives of Gerontology and Geriatrics, 4, 2.12%
Journal of Nutrition, Health and Aging
Journal of Nutrition, Health and Aging, 4, 2.12%
Frontiers in Medicine
Frontiers in Medicine, 3, 1.59%
Cancers
Cancers, 3, 1.59%
Scientific Reports
Scientific Reports, 3, 1.59%
Frontiers in Nutrition
Frontiers in Nutrition, 3, 1.59%
Journal of Cachexia, Sarcopenia and Muscle
Journal of Cachexia, Sarcopenia and Muscle, 3, 1.59%
Journal of Clinical Medicine
Journal of Clinical Medicine, 3, 1.59%
Frontiers in Physiology
Frontiers in Physiology, 2, 1.06%
Healthcare
Healthcare, 2, 1.06%
European Geriatric Medicine
European Geriatric Medicine, 2, 1.06%
Aging Cell
Aging Cell, 2, 1.06%
Clinical Interventions in Aging
Clinical Interventions in Aging, 2, 1.06%
Medicine (United States)
Medicine (United States), 2, 1.06%
Nature and Science of Sleep
Nature and Science of Sleep, 2, 1.06%
BMC Cardiovascular Disorders
BMC Cardiovascular Disorders, 2, 1.06%
Immunity and Ageing
Immunity and Ageing, 2, 1.06%
Journal of Clinical Nursing
Journal of Clinical Nursing, 2, 1.06%
Medicina
Medicina, 2, 1.06%
Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 2, 1.06%
Maturitas
Maturitas, 2, 1.06%
Journal of Translational Medicine
Journal of Translational Medicine, 1, 0.53%
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Publishers

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Elsevier
Elsevier, 44, 23.28%
Springer Nature
Springer Nature, 38, 20.11%
MDPI
MDPI, 30, 15.87%
Frontiers Media S.A.
Frontiers Media S.A., 22, 11.64%
Wiley
Wiley, 17, 8.99%
Taylor & Francis
Taylor & Francis, 7, 3.7%
Oxford University Press
Oxford University Press, 6, 3.17%
Ovid Technologies (Wolters Kluwer Health)
Ovid Technologies (Wolters Kluwer Health), 5, 2.65%
SAGE
SAGE, 5, 2.65%
Research Square Platform LLC, 2, 1.06%
BMJ
BMJ, 1, 0.53%
International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA), 1, 0.53%
Hans Publishers
Hans Publishers, 1, 0.53%
Human Kinetics
Human Kinetics, 1, 0.53%
S. Karger AG
S. Karger AG, 1, 0.53%
China Science Publishing & Media, 1, 0.53%
Cold Spring Harbor Laboratory
Cold Spring Harbor Laboratory, 1, 0.53%
The Japanese Association of Rehabilitation Medicine, 1, 0.53%
American Association for the Advancement of Science (AAAS)
American Association for the Advancement of Science (AAAS), 1, 0.53%
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