Dataset Information

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.

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 1?), 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.

SUBMITTER: Marzetti E

PROVIDER: S-EPMC7536309 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

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 Emanuele E Guerra Flora F Calvani Riccardo R Marini Federico F Biancolillo Alessandra A Gervasoni Jacopo J Primiano Aniello A Coelho-Júnior Hélio José HJ Landi Francesco F Bernabei Roberto R Bucci Cecilia C Picca Anna A

Frontiers in cell and developmental biology 20200922

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 ...[more]

PMID: 33072749

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Project description:BackgroundPatients with end-stage renal disease (ESRD) are at an increased risk of developing sarcopenia, which can lead to various adverse health outcomes. Although the diagnosis of sarcopenia is essential for clinical management, it is not feasible in routine clinical practice for populations undergoing haemodialysis because it is time-consuming and resources are limited. Serum creatinine levels in patients with ESRD have been gaining attention as a screening parameter for sarcopenia because serum creatinine is a routinely measured byproduct of skeletal muscle metabolism. This study aimed to evaluate the discriminative ability of the creatinine-derived index for sarcopenia in patients undergoing haemodialysis.MethodsWe diagnosed sarcopenia according to the Asian Working Group for Sarcopenia (AWGS) 2 criteria in 356 clinically stable outpatients with ESRD enrolled from three dialysis facilities. We adopted the modified creatinine index as a simplified discriminant parameter for sarcopenia in addition to the calf circumference, SARC-F score, and combination of both (i.e. SARC-CalF score), which are recommended by the AWGS. Receiver operating characteristic analysis and logistic regression analysis were conducted to evaluate the discriminative ability of the modified creatinine index for sarcopenia.ResultsOf the study participants, 142 (39.9%) were diagnosed with sarcopenia. The areas under the curve of the modified creatinine index against sarcopenia in the male and female participants were 0.77 (95% confidence interval [CI]: 0.71 to 0.83) and 0.77 (95% CI: 0.69 to 0.85), respectively. All simplified discriminant parameters were significantly associated with sarcopenia, even after adjusting for patient characteristics and centre. In the comparison of the odds ratios for sarcopenia for 1-standard deviation change in the simplified discriminant parameters, the odds ratio of the modified creatinine index was 1.92 (95% CI: 1.15 to 3.19), which was lower than that of the calf circumference (odds ratio: 6.58, 95% CI: 3.32 to 13.0) and similar to that of the SARC-F (odds ratio: 1.57, 95% CI: 1.14 to 2.16) and SARC-CalF scores (odds ratio: 2.36, 95% CI: 1.60 to 3.47).ConclusionsThis study revealed a strong association between the creatinine-derived index and sarcopenia in patients undergoing haemodialysis. The modified creatinine index was equal or superior to those of SARC-F and SARC-CalF score in discriminability for sarcopenia. However, the ability of the calf circumference to discriminate sarcopenia is extremely high, and further study is needed to determine whether it can be used to detect deterioration of muscle mass and function over time.

Project description:Musculoskeletal aging is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Bone and muscle tissues were increasingly recognized, as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. During growth, bone mineral content closely correlates with muscle mass, and several evidences suggest that osteoporosis and sarcopenia present common pathophysiological factors and show the correlation between low bone mineral density and sarcopenia in both men and women. Then, sarcopenia and osteoporosis, typical features of aging, are often associated with each other and with the frailty syndrome. In particular, sarcopenia and osteoporosis are major contributors to disability and frailty and the common denominators are age-related chronic inflammation, changes in body composition and hormonal imbalance. Frailty syndrome is characterized by a reduced response to stress, triggering the decline of the physiological functioning of the various systems. Frailty syndrome, typical of the older people, is frequently associated with a reduction in the quality of life and mobility. Falls often are the basis of reduced mobility and ability to perform the common functions of daily life and the increase in the number of institutionalizations. Moreover, the reduction of muscle mass, associated with altered muscle composition, fat and fibrous infiltration and alterations in innervations, and the increase in fat mass, have a synergistic effect on the increase in cardiovascular risk. The aim of this review is to analyze the pathophysiological mechanisms underlying the frailty syndrome and its association with sarcopenia and osteoporosis, and investigate possible intervention measures.

Dataset Information

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.

Publications

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.

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