Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients
Hettwer S, Dahinden P, Kucsera S, Farina C, Ahmed S, Fariello R, Drey M, Sieber C, Vrijbloed JW (2013)
Publication Status: Published
Publication Type: Journal article
Publication year: 2013
Journal
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Book Volume: 48
Pages Range: 69-75
Journal Issue: 1
DOI: 10.1016/j.exger.2012.03.002
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.
Authors with CRIS profile
Michael Drey
Lehrstuhl für Innere Medizin (Geriatrie)
Cornel Sieber
Lehrstuhl für Innere Medizin (Geriatrie)
Involved external institutions
Switzerland (CH)How to cite
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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