Increased plasma proline concentrations are associated with sarcopenia in the elderly

Toyoshima, Kenji; Nakamura, Marie; Adachi, Yusuke; Imaizumi, Akira; Hakamada, T; Abe, Yasuko; Kaneko, Eiji; Takahashi, Soiciro; Shimokado, Kentaro

doi:10.1371/journal.pone.0185206

Cited by 55 publications

(53 citation statements)

References 44 publications

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“…These metabolic changes seem to compensate for the reduction in energy production from pyruvic acid in the skeletal muscle. Indeed, the Pro level was significantly elevated in the mice fed the Trp-deficient diet, which concurs with the data describing the serum amino acids associated with sarcopenia in older people [7]. Glucose is the main energy fuel for humans and is stored as glycogen, primarily in the liver and skeletal muscle.…”

Section: Discussionsupporting

confidence: 89%

“…Recently, metabolomics analysis has been used to understand how amino acid profiles are affected by glucose metabolism [4], aging [5], and cancer [6]. Toyoshima et al [7] have reported an association between plasma amino acid profiles and age-related sarcopenia, and demonstrated that sarcopenia was correlated with lower tryptophan (Trp) and histidine (His) and higher glutamine (Gln) and proline (Pro) concentrations. Furthermore, plasma Trp and His concentrations are often reduced in patients with particular types of cancer [8].…”

Section: Introductionmentioning

confidence: 99%

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Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Ninomiya

Nakamura

et al. 2020

Nutrients

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Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Ninomiya

Nakamura

et al. 2020

Nutrients

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“…2a). Plasma amino acid profiling of patients with sarcopenia—a condition of muscle wasting associated with aging—showed elevated plasma proline levels 29 , indicating that elevated free circulating proline is a common feature of muscle wasting. We identify a proline vulnerability of obesity-enhanced tumours; SLC36-family proline transporter Path is required for tumour growth and exogenous proline promotes tumourigenesis through Path (Fig.…”

Section: Discussionmentioning

confidence: 99%

Systemic muscle wasting and coordinated tumour response drive tumourigenesis

Newton

Wang

Camplese

et al. 2019

Preprint

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SUMMARYCancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic pertubations remain incompletely understood. Here we use a Drosophila model of obesity-enhanced tumourigenesis to uncover a systemic host-tumour nutrient circuit that supports tumour growth. We demonstrate coordinate induction of systemic cachexia-like muscle wasting with tumour-autonomous SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. This coordinated induction of cachexia and SLC36-transporters pertains to human kidney cancer and associates with significantly worse survival outcomes. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Combining insights from whole-animal Drosophila models and human cancer database analysis provides a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of perturbed systemic metabolic network.

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“…14 A total of 25 participants with sarcopenia or cognitive impairments were excluded, because these age-related disorders potentially affect plasma amino acids. [15][16][17] Eight participants with missing data were also excluded. The present study was carried out in accordance with the Declaration of Helsinki, and the study protocol was approved by the ethics committees of the Tokyo Medical and Dental University (#2146) and Ajinomoto (#2015-009).…”

Section: Methodsmentioning

confidence: 99%

Association between plasma α‐aminobutyric acid and depressive symptoms in older community‐dwelling adults in Japan

Adachi

Toyoshima

Nishimoto

et al. 2018

Geriatrics Gerontology Int

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Aim To examine the association between depressive symptoms and plasma amino acid related metaboli in older adults. Methods A total of 152 older adults aged ≥65 years, residing in Niigata, Japan, were used for analysis. We evaluated depressive symptoms using the Geriatric Depression Scale‐15, which has been validated in older community‐dwelling individuals, and used a cut off score of ≥5 to classify participants as having depressive symptoms. We used high‐performance liquid chromatography‐electrospray ionization mass spectrometry to measure the concentrations of plasma amino acid‐related metabolites, and carried out logistic regression analysis to assess the association between depressive symptoms and plasma amino acid‐related metabolites. Results Of the 119 older adults (mean age 76.3 years) included in the analysis, 22 were classified as having depressive symptoms (depressive group). There were no significant differences in physical and cognitive impairments between participants in the depressive and non‐depressive groups. The plasma α‐aminobutyric acid (AABA) level was significantly lower in the depressive group than in the non‐depressive group (P < 0.001). Logistic regression analysis showed the best‐fit model, which included AABA, leucine, threonine, hydroxyl proline and histidine levels (area under the receiver operating characteristic curve 0.8346; 95% confidence interval 0.7365–0.9326). In particular, the plasma AABA level was strongly associated with depressive symptoms. Conclusions Plasma AABA level is significantly associated with depression symptoms in older community‐dwelling adults in Japan. Thus, plasma AABA might serve as a potential marker of depression in older adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 254–258.

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Increased plasma proline concentrations are associated with sarcopenia in the elderly

Cited by 55 publications

References 44 publications

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Systemic muscle wasting and coordinated tumour response drive tumourigenesis

Association between plasma α‐aminobutyric acid and depressive symptoms in older community‐dwelling adults in Japan

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