Frailty Status in Older Adults Is Related to Alterations in Indoleamine 2,3-Dioxygenase 1 and Guanosine Triphosphate Cyclohydrolase I Enzymatic Pathways

Marcos-Pérez, Diego; Sánchez-Flores, María; Maseda, Ana; Lorenzo-López, Laura; Millán-Calentí, José Carlos; Strasser, Barbara; Gostner, Johanna M.; Fuchs, Dietmar; Pásaro, Eduardo; Valdiglesias, Vanessa; Laffón, Blanca

doi:10.1016/j.jamda.2017.06.021

Cited by 41 publications

(37 citation statements)

References 76 publications

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“…Tryptophan is metabolized via two major pathways, the tryptophan-kynurenine and the tryptophan-methoxyndole pathways, that lead to the production of NAD, serotonin, and melatonin [72]. Alterations in tryptophan metabolism have been described in the context of frailty and T2DM [73,74]. In particular, tryptophan and its associated metabolites have been associated with insulin resistance and incident T2DM in independent cohorts [74,75].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

et al. 2020

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Diabetes and frailty are highly prevalent conditions that impact the health status of older adults. Perturbations in protein/amino acid metabolism are associated with both functional impairment and type 2 diabetes mellitus (T2DM). In the present study, we compared the concentrations of a panel of circulating 37 amino acids and derivatives between frail/pre-frail older adults with T2DM and robust non-diabetic controls. Sixty-six functionally impaired older persons aged 70+ with T2DM and 30 age and sex-matched controls were included in the analysis. We applied a partial least squares-discriminant analysis (PLS-DA)-based analytical strategy to characterize the metabotype of study participants. The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 94.1 ± 1.9% for frail/pre-frail persons with T2DM and 100% for control participants. Functionally impaired older persons with T2DM showed higher levels of 3-methyl histidine, alanine, arginine, glutamic acid, ethanolamine sarcosine, and tryptophan. Control participants had higher levels of ornithine and taurine. These findings indicate that a specific profile of amino acids and derivatives characterizes pre-frail/frail older persons with T2DM. The dissection of these pathways may provide novel insights into the metabolic perturbations involved in the disabling cascade in older persons with T2DM.

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Section: Discussionmentioning

confidence: 99%

Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

et al. 2020

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“…With the aim of developing biomarkers of frailty, our group has investigated the potential association of frailty status with different genetic and immunological outcomes (30,32). In a very recent study (30), we evaluated the suitability of micronucleus frequency-a biomarker of genomic instability-to be employed as frailty biomarker.…”

Section: Discussionmentioning

confidence: 99%

Exploring Genetic Outcomes as Frailty Biomarkers

Valdiglesias

Sánchez-Flores

Marcos-Pérez

et al. 2018

The Journals of Gerontology: Series A

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Frailty has emerged as a reliable measure of the aging process. Since the early detection of frailty is crucial to prevent or even revert it, the use of biomarkers would allow an earlier and more objective identification of frail individuals. In order to improve the understanding of the biological features associated with frailty as well as to explore different biomarkers for its early identification, several genetic outcomes - mutagenicity, different types of genetic damage, and cellular repair capacity - were analysed in a population of older adults classified into frail, pre-frail and non-frail. Besides, influence of clinical parameters - nutritional status and cognitive status - was evaluated. No association of mutation rate or primary DNA damage with frailty was observed. However, DNA repair capacity showed a non-significant tendency to decrease with frailty, and persistent levels of phosphorylated H2AX, as indicative of DNA breakage, increased progressively with frailty severity. These results support the possible use of H2AX phosphorylation to provide information regarding frailty severity. Further investigation is necessary to determine the consistency of the current findings in different populations and larger sample sizes, to eventually standardize biomarkers to be used in clinics, and to fully understand the influence of cognitive impairment.

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“…Inflammaging has been postulated to be an underlying mechanism of frailty, acting either directly or indirectly through its negative influence on other physiological systems ( 23 , 24 ). Thus, studies testing the hypothesis that frailty is associated with alterations in the concentration of immune activation markers, pro-inflammatory molecules, and in different lymphocyte subpopulations are increasing in the last years ( 25 – 29 ), although clear definitive conclusions have not been reached yet.…”

Section: Introductionmentioning

confidence: 99%

Frailty in Older Adults Is Associated With Plasma Concentrations of Inflammatory Mediators but Not With Lymphocyte Subpopulations

et al. 2018

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Frailty denotes a multidimensional syndrome that gives rise to vulnerability to stressors and leads to an increase of the age-related decline of different physiological systems and cognitive abilities. Aging-related alterations of the immune system may compromise its competence culminating in a chronic low-grade inflammation state. Thus, it has been proposed that frailty is associated with alterations in the concentration of pro-inflammatory molecules and in different lymphocyte subpopulations. To provide further support to the validity of that hypothesis, we conducted a cross-sectional study in a population of Spanish older adults (N = 259, aged 65 and over) classified according to their frailty status. Biomarkers analyzed included percentages of several lymphocyte subsets and several inflammation mediators, namely concentrations of interleukin 6 (IL6), C-reactive protein (CRP), tumor necrosis factor α (TNFα), and 75 kDa soluble TNFα receptor II (sTNF-RII). Reference ranges for the inflammation mediators were established for the first time in robust older adults. A significant increase in the CD4+/CD8+ ratio and a significant decrease in the % CD19+ cells were observed in the frail group. Progressive increases with frailty severity were obtained in all inflammatory mediator concentrations, especially notable for IL6 and sTNF-RII. Area under the receiver-operating characteristic curve obtained for sTNF-RII (0.90, 95% CI 0.85–0.94, P < 0.001) indicates a high accuracy in the predictive value of this biomarker for frailty. Although results from the current study revealed limited strength associations between frailty and the lymphocyte subsets assessed, data obtained for the inflammatory mediators provide further support to involvement of inflammaging in frailty status in older adults.

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Frailty Status in Older Adults Is Related to Alterations in Indoleamine 2,3-Dioxygenase 1 and Guanosine Triphosphate Cyclohydrolase I Enzymatic Pathways

Cited by 41 publications

References 76 publications

Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

Exploring Genetic Outcomes as Frailty Biomarkers

Frailty in Older Adults Is Associated With Plasma Concentrations of Inflammatory Mediators but Not With Lymphocyte Subpopulations

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