{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:36:31Z","timestamp":1784824591218,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,4,16]],"date-time":"2017-04-16T00:00:00Z","timestamp":1492300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast\u2010twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow\u2010twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre\u2010type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle\u2010specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real\u2010time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region\u2014but mainly in the fast\u2010twitch, not the slow\u2010twitch, muscle of old mice. We further found that the protein kinase A (PKA) RI\u03b1 subunit was largely removed from, while PKA RII\u03b1 and RII\u03b2 are enriched at, the NMJ\u2014again, preferentially in fast\u2010twitch but not slow\u2010twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RI\u03b1 and reduced PKA RII\u03b1 at the NMJ; (ii) decreased the levels of gene expression of muscle denervation markers; and (iii) enhanced neurotransmission efficiency at NMJ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cardiac troponin T at the NMJ region contributes to NMJ functional decline with ageing mainly in the fast\u2010twitch skeletal muscle through interfering with PKA signalling. This knowledge could inform useful targets for prevention and therapy of age\u2010related decline in muscle function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12204","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T04:56:51Z","timestamp":1492405011000},"page":"808-823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cardiac troponin T and fast skeletal muscle denervation in ageing"],"prefix":"10.1002","volume":"8","author":[{"given":"Zherong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section on Gerontology and Geriatic Medicine Wake Forest School of Medicine  Winston\u2010Salem NC USA"},{"name":"Department of Geriatrics First Affiliated Hospital, Zhejiang University, School of Medicine  Hangzhou 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