Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients

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Details zur Publikation

Autorinnen und Autoren: Hettwer S, Dahinden P, Kucsera S, Farina C, Ahmed S, Fariello R, Drey M, Sieber C, Vrijbloed JW
Zeitschrift: Experimental Gerontology
Verlag: PERGAMON-ELSEVIER SCIENCE LTD
Jahr der Veröffentlichung: 2013
Band: 48
Heftnummer: 1
Seitenbereich: 69-75
ISSN: 0531-5565


Abstract

Sarcopenia is a recently defined medical condition described as age-associated loss of skeletal muscle mass and function. Recently, a transgenic mouse model was described linking dispersal of the neuromuscular junction caused by elevated agrin degradation to the rapid onset of sarcopenia. These mice show a significant elevation of serum levels of a C-terminal agrin fragment (CAF) compared to wild-type littermates. A series of experiments was designed to ascertain the significance of elevated agrin degradation in the development of human sarcopenia. A quantitative Western blot method was devised to detect CAF in sera of humans. A first trial on consenting blood donors (n=169; age 19-74 years) detected CAF in the limited range of 2.76 +/- 0.95 ng/ml. In sarcopenia patients (diagnosed according to clinical and instrumental standards) mean CAF levels were significantly elevated (p=9.8E10-9; n=73; age 65-87 years) compared to aged matched controls. Of all sarcopenia patients, 40% had elevated, non-overlapping CAF levels compared to controls. Evidence is presented for a pathogenic role of the agrin/neurotrypsin system in a substantial subset of sarcopenia patients. These patients are characterized by elevated CAF blood levels compared to aged-matched healthy volunteers suggesting the identification of an agrin-dependent form of sarcopenia. Elevated CAF levels in a large subpopulation of sarcopenic patients suggest the existence of a specific form of sarcopenia for which CAF could become a biomarker and a new target for therapeutic interventions. The feasibility of this approach was demonstrated by the development of a small molecule capable of inhibiting neurotrypsin in vitro and in vivo. (C) 2012 Elsevier Inc. All rights reserved.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Drey, Michael Dr.
Lehrstuhl für Innere Medizin (Geriatrie)
Sieber, Cornel Prof. Dr.
Lehrstuhl für Innere Medizin (Geriatrie)


Einrichtungen weiterer Autorinnen und Autoren

Neurotune AG


Zitierweisen

APA:
Hettwer, S., Dahinden, P., Kucsera, S., Farina, C., Ahmed, S., Fariello, R.,... Vrijbloed, J.W. (2013). Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients. Experimental Gerontology, 48(1), 69-75. https://dx.doi.org/10.1016/j.exger.2012.03.002

MLA:
Hettwer, Stefan, et al. "Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients." Experimental Gerontology 48.1 (2013): 69-75.

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Zuletzt aktualisiert 2018-18-10 um 21:08