Omics biomarkers for frailty in older adults

Pan, Yiming; Ji, Tong; Li, Yun; Ma, Lina

doi:10.1016/j.cca.2020.07.057

Cited by 17 publications

(14 citation statements)

References 79 publications

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“…Related biomarkers of frailty can be used in diagnosis and treatment decisions concerning frailty (38,39). As a reflection of the comprehensive interaction between the genome and environment at the individual level, metabolomics methods are increasingly becoming the preferred approach to uncover frailty-contributing biomarkers and explore the mechanismof frailty (11)(12)(13). To our knowledge, the relationship of frailty with AcyCNs and LPCs, as well as amino acids, in older adults has not been well characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating metabolites have emerged as a possible tool for capturing this complexity and hold the potential to identify metabolic factors or biomarkers that contribute to frailty, offering opportunities to develop strategies for its identification and management (9,10). However, there is a lack of stable and reliable frailty-related biomarkers for use in clinical practice (11,12). Moreover, the various biomarkers for frailty thus far discovered in metabolomics have focused mostly on amino acids (13,14), and relatively less is known about the association of frailty with lipid metabilism such as carnitine, acylcarnitines (AcyCNs) and lysophosphatidylcholines (LPCs), in part because of their structural diversity and the sheer number of discrete molecular species (15).…”

Section: Introductionmentioning

confidence: 99%

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Specific Metabolites Involved in Antioxidation and Mitochondrial Function Are Correlated With Frailty in Elderly Men

Shi

Wang

et al. 2022

Front. Med.

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BackgroundAs an age-related syndrome, frailty may play a central role in poor health among older adults. Sarcopenia overlaps with the physical domain of frailty, and most existing studies have analyzed the associated factors of frailty and sarcopenia as an isolated state. Perturbations in metabolism may play an important role in the presence of frailty or sarcopenia; however, the metabolites associated with frailty, especially overlapping with sarcopenia remain unclear. In this study, we aimed to explore whether amino acids, carnitines, acylcarnitines and lysophosphatidylcholines, as specific panels, are significantly correlated with frailty, especially overlapping with sarcopenia, to gain insight into potential biomarkers and possible biological mechanisms and to facilitate their management.MethodsWe applied a targeted high-performance liquid chromatography-tandem mass spectrometry approach in serum samples from 246 Chinese older men (age 79.2 ± 7.8 years) with frailty (n = 150), non-frailty (n = 96), frailty and sarcopenia (n = 52), non-frail and non-sarcopenic control (n = 85). Frailty was evaluated using Freid phenotype criteria, sarcopenia was defined by diagnostic algorithm of Asian Working Group on Sarcopenia, and the participants were diagnosed as frailty and sarcopenia when they met the evaluation criteria of both frailty and sarcopenia. A panel of 29 metabolomic profiles was assayed and included different classes of amino acids, carnitines, acylcarnitines, and lysophosphatidylcholines (LPCs). Multivariate logistic regression was used to screen the metabolic factors contributing to frailty status, and orthogonal partial least squares discriminant analysis was used to explore important factors and distinguish different groups.ResultsIn older men demonstrating the frail phenotype, amino acid perturbations included lower tryptophan and higher glycine levels. With regard to lipid metabolism, the frailty phenotype was characterized by lower concentrations of isovalerylcarnitine (C5), LPC16:0 and LPC18:2, while higher levels of octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14). After adjusting for several clinical confounders, tryptophan, LPC18:2, LPC 16:0 and C5 were negatively correlated with frailty, and C8 and C12 were positively related to frailty. We preliminarily identified metabolic profiles (LPC16:0, LPC18:2, glycine and tryptophan) that may distinguish older men with frailty from those without frailty. Importantly, a set of serum amino acids and LPCs (LPC16:0, LPC18:2, and tryptophan) was characterized in the metabotype of older adults with an overlap of frailty and sarcopenia. The metabolites that were most discriminating of frailty status implied that the underlying mechanism might be involved in antioxidation and mitochondrial dysfunction.ConclusionsThese present metabolic analyses may provide valuable information on the potential biomarkers and possible biological mechanisms of frailty, and overlapping sarcopenia. The findings obtained may offer insight into their management in older adults.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specific Metabolites Involved in Antioxidation and Mitochondrial Function Are Correlated With Frailty in Elderly Men

Shi

Wang

et al. 2022

Front. Med.

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“…In the last years, many efforts have been made to understand the molecular mechanisms underlying frailty [ 8 ] and to find biomarkers for a correct diagnosis [ 9 ]. Research evidence suggests that, among the cellular mechanisms that might underlie frailty, senescence, oxidative stress, mitochondrial dysfunctions, and inflammation have major roles in frailty pathophysiology [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, despite the progress in identifying biomarkers of frailty in recent years, currently there is not a clear consensus. Different studies have identified promising candidates including markers across the immune system, endocrine system, clinical blood markers, proteins, markers of oxidative damage, and epigenetic markers [ 8 , 12 , 13 ]. Among the latter, microRNAs (miRNAs) are emerging as promising non-invasive diagnostic and prognostic biomarkers, as well as potential therapeutic agents [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

miRNome Profiling Detects miR-101-3p and miR-142-5p as Putative Blood Biomarkers of Frailty Syndrome

Carini

Mingardi

Bolzetta³

et al. 2022

Genes

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Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this study was to identify blood miRNAs that could serve as potential biomarkers and candidate mechanisms of frailty. Using the Fried index, we enrolled 22 robust and 19 frail subjects. Blood and urine samples were analysed for several biochemical parameters. We observed that sTNF-R was robustly upregulated in the frail group, indicating the presence of an inflammatory state. Further, by RNA-seq, we profiled 2654 mature miRNAs in the whole blood of the two groups. Expression levels of selected differentially expressed miRNAs were validated by qPCR, and target prediction analyses were performed for the dysregulated miRNAs. We identified 2 miRNAs able to significantly differentiate frail patients from robust subjects. Both miR-101-3p and miR-142-5p were found to be downregulated in the frail vs. robust group. Finally, using bioinformatics targets prediction tools, we explored the potential molecular mechanisms and cellular pathways regulated by the two miRNAs and potentially involved in frailty.

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“…Third, the increasing use of omics-based technologies in frailty research represents a new frontier in a quest to identify novel biological molecules and mechanisms responsible for the generalized physiological dysregulation associated with frailty [ 25 ]. However, it is important to recognize that the large number of parameters involved in omics studies raise significant challenges for data analysis, particularly when the number of study subjects is limited.…”

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confidence: 99%