Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects

Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or infla...

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Published inNutrients Vol. 11; no. 4; p. 895
Main Author Ingenbleek, Yves
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 21.04.2019
MDPI
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ISSN2072-6643
2072-6643
DOI10.3390/nu11040895

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Abstract Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.
AbstractList Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.
[...]many aspects of the physiopathology of sarcopenia have not been fully elucidated and thus require additional tools for the diagnosis and follow-up of muscle composition and function [5]. [...]the emergence of sarcopenic obesity and its multiple subclasses has added to the overall confusion, prompting the mandatory need to disentangle the muddle. [...]new methodologies were developed, allowing to distinguish fat mass and lean mass from body mineral content [17] and to assess the regional size of muscle mass [18]. [...]a double burden of diseases has spread worldwide, combining protein shortage with the unavoidable trail of noncommunicable diseases [63,64]. The disproportionate inflation of fat stores in a rising obesogenic environment had the negative effect to obliterate the nutritional criteria of malnutrition, notably those defining the size and strength of muscle mass. [...]the discrepancy between FM and SM data was aggravated by the recently proposed metabolic dissection of adiposity distribution into four different subsets (central, peripheral, android, gynoid) [70], each of which being characterized by specific impacts on risks of complications, length of hospital stay, fatal outcome, and hospital costs.
Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.
Author Ingenbleek, Yves
AuthorAffiliation Laboratory of Nutrition, Faculty of Pharmacy, University Louis Pasteur, F-67401 Strasbourg, France; ingen@unistra.fr
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Keywords lean body mass
malnutrition
elderly persons
inflammation
transthyretin
diagnosis
prognosis
outcome
sarcopenia
Language English
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Snippet Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age....
[...]many aspects of the physiopathology of sarcopenia have not been fully elucidated and thus require additional tools for the diagnosis and follow-up of...
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SubjectTerms Adipose Tissue
Aged
Biomarkers
Biomarkers - blood
Body Composition
Body Fluid Compartments - metabolism
Body Mass Index
clinical trials
elderly
experts
Health care
Humans
Inflammation - blood
Kidneys
lean body mass
Liver
Liver - metabolism
Malnutrition
Medical prognosis
metabolism
Mortality
Muscle, Skeletal - metabolism
NMR
Nuclear magnetic resonance
nutrient deficiencies
Nutritional Status
obesity
Obesity - complications
patients
Peritoneal dialysis
prealbumin
Prealbumin - biosynthesis
Prealbumin - metabolism
Protein Deficiency - blood
Proteins
Review
Sarcopenia
Sarcopenia - blood
screening
skeletal muscle
surveys
therapeutics
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