A neurogenic perspective of Sarcopenia: time course study of sciatic nerves from aging mice
Open accessAbstract
To elucidate the neural basis for age-related sarcopenia, we quantified morphologic and molecular changes within sciatic nerves of aging male and female C57BL/6J mice aged between 3 and 27 months using immunoblotting, immunohistochemistry, and electron microscopy. Protein analyses by immunoblotting of nerves of male mice aged 4, 15, 18, 22, and 24 months showed increased levels of heavy chain SMI-32-positive neurofilaments, vimentin, tau5, choline acetyltransferase (ChAT), and p62 by 18-22 months. Similar protein increases were seen in 26-month-old compared with 3-month-old female mice. Immunostaining of longitudinal sections of old (27-month-old) male sciatic nerves revealed intense staining for tau5 and p62 that was increased compared with that at 3 months, but there were decreased numbers of axon profiles stained for ChAT or isolectin B4 (motor and sensory axons, respectively). Ultrastructural analysis revealed electron-dense aggregates within axons in peripheral nerves of old male mice; the proportion of axons that contained aggregates more than doubled between 15 and 27 months. Overall, the observed age-related accumulation of many proteins from about 18 months of age onward suggests impaired mechanisms for axonal transport and protein turnover. These peripheral nerve changes may contribute to the morphological and functional muscle deficits associated with sarcopenia.
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Denervation and neuromuscular dysfunction are important contributors to sarcopenia.
“Denervation and neuromuscular dysfunction are well-recognized as important contributors to sarcopenia.”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Krishnan et al., 2016
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Physical activity and muscle-brain crosstalk
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- Authors
- Krishnan, V. S., White, Z., McMahon, C. D., Hodgetts, S. I., Fitzgerald, M., Shavlakadze, T., Harvey, A. R., & Grounds, M. D.
- Affiliations
- The University of Western Australia (AU)
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-03-30
- Volume
- 75
- Issue
- 5
- Pages
- 464-478
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2334243160
- Cited by
- 32
- References
- 119
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 2
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (University of Western Australia) (acceptedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- eSpace (Curtin University) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Curtin University of Technology
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- sarcopenia, aging, sciatic nerve, peripheral nerve degeneration, neurofilaments, p62, choline acetyltransferase, axonal transport, protein turnover, sex differences, age-related muscle loss, C57BL/6J mice
- MeSH terms
- Age Factors, Aging, Animals, Female, Male, Mice, Inbred C57BL, Sciatic Nerve, Mice, Sarcopenia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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