Motoneuron Loss Is Associated With Sarcopenia

Drey, Michael; Krieger, Benjamin; Sieber, Cornel; Bauer, Jürgen; Hettwer, Stefan; Bertsch, Thomas; Dahinden, Pius; Mäder, Armin; Vrijbloed, Jan W.; Schuster, G.M.; Zollinger, Stefan; Beeler, Christoph; Unterer, Thomas

doi:10.1016/j.jamda.2014.02.002

Cited by 102 publications

(79 citation statements)

References 36 publications

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“…Even in sarcopenia, the age-related loss of skeletal muscle mass, a strong association between motoneuron impairment and the degree of muscle wasting has been established. Indeed, numerous studies showed that degeneration and loss of motor neurons followed by structural and functional changes in innervations, significantly contribute to the progression of sarcopenia [50][51][52]. Considering the central role in mediating skeletal muscle nerve response, several studies indicated HDAC4 as a potential therapeutic target for the prevention of neurogenic muscle atrophy in pathological conditions or during aging [38,53].…”

Section: Discussionmentioning

confidence: 99%

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

et al. 2018

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Background: Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. Methods: To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. Results: After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitinproteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. Conclusions: These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

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Section: Discussionmentioning

confidence: 99%

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

et al. 2018

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“…1). There is an aging-related progressive loss of motor neurons innervating limb muscles (Brown, 1972; Kwan, 2013; Lexell et al, 1988; McNeil et al, 2005; Rosenheimer, 1990; Tomlinson and Irving, 1977) that is correlated with the presence of sarcopenia (Drey et al, 2014). This frank loss of motor neurons results in denervation of muscle fibers, with possible reinnervation by remaining motor neurons (via axonal sprouting), and consequent motor unit expansion (Gordon and Stein, 1982).…”

Section: Aging-related Motor Neuron Loss and Sarcopeniamentioning

confidence: 99%

Functional impact of sarcopenia in respiratory muscles

Elliott

Greising

Mantilla

et al. 2016

Respiratory Physiology & Neurobiology

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The risk for respiratory complications and infections is substantially increased in old age, which may be due, in part, to sarcopenia (aging-related weakness and atrophy) of the diaphragm muscle (DIAm), reducing its force generating capacity and impairing the ability to perform expulsive non-ventilatory motor behaviors critical for airway clearance. The aging-related reduction in DIAm force generating capacity is due to selective atrophy of higher force generating type IIx and/or IIb muscle fibers, whereas lower force generating type I and IIa muscle fiber sizes are preserved. Fiber type specific DIAm atrophy is also seen following unilateral phrenic nerve denervation and in other neurodegenerative disorders. Accordingly, the effect of aging on DIAm function resembles that of neurodegeneration and suggests possible common mechanisms, such as the involvement of several neurotrophic factors in mediating DIAm sarcopenia. This review will focus on changes in two neurotrophic signaling pathways that represent potential mechanisms underlying the aging-related fiber type specific DIAm atrophy.

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“…The loss of motoneurons accompanied by reduction of the muscle mass was present in 23% of sarcopenic patients. 19 Loss of muscle mass is seen frequently after stroke. 20e22 As early as 3 weeks after stroke, a significant decline of muscle mass has been observed.…”

Section: Denervation and Muscle Mass Lossmentioning

confidence: 99%