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Sarcopenia, the progressive loss of muscle mass and function, universally affects older adults and is closely associated with frailty and reduced quality of life. Despite the inevitable consequences of sarcopenia and its relevance to healthspan, no pharmacological therapies are currently available. Ghrelin is a gut‐released hormone that increases appetite and body weight through acylation. Acylated ghrelin activates its receptor, growth hormone secretagogue receptor 1a (GHSR1a), in the brain by binding to it. Studies have demonstrated that acyl and unacylated ghrelin (UnAG) both have protective effects against acute pathological conditions independent of receptor activation. Here, we investigated the long‐term effects of UnAG in age‐associated muscle atrophy and contractile dysfunction in mice. Four‐month‐old and 18‐month‐old mice were subjected to either UnAG or control treatment for 10 months. UnAG did not affect food consumption or body weight. Gastrocnemius and quadriceps muscle weights were reduced by 20%–30% with age, which was partially protected against by UnAG. Specific force, force per cross‐sectional area, measured in isolated extensor digitorum longus muscle was diminished by 30% in old mice; however, UnAG prevented the loss of specific force. UnAG also protected from decreases in mitochondrial respiration and increases in hydrogen peroxide generation of skeletal muscle of old mice. Results of bulk mRNA‐seq analysis and our contractile function data show that UnAG reversed neuromuscular junction impairment that occurs with age. Collectively, our data revealed the direct role of UnAG in mitigating sarcopenia in mice, independent of food consumption or body weight, implicating UnAG treatment as a potential therapy against sarcopenia. [ABSTRACT FROM AUTHOR]

Peripheral nerve damage is a critical disorder causing disability of locomotion. The aim of the study was to clarify the effects of testosterone and tacrolimus on the gastrocnemius muscle following sciatic injury. The study was done on 20 rats (n = 5 in each group) whose left sciatic nerve was crushed for 10 s. The sham group (S) of animals received no medicine; the testosterone group (Tes) received testosterone (5 mg/kg, s.c.); the tacrolimus group (Tac): received tacrolimus (5 mg/kg, p.o.); the testosterone and tacrolimus group (Tes+Tac) received testosterone (5 mg/kg, s.c.) and tacrolimus (5 mg/kg, p.o.) daily for four weeks. The gastrocnemius was assessed by gross observation of the plantar surface of paws; the pelvic limb mass muscle and the muscle diameter ratio of the left pelvic limb to the right one by ultrasonography. The gastrocnemius muscle index (GMI) of the left and right pelvic limb, muscle colour, and pathologic changes were also studied. Pathology study of the gastrocnemius included fatty infiltration, muscle atrophy, presence of inflammatory cells and fibrosis formation. Heel redness and swelling were seen in group Tac. No significant difference was found in the GMI between the Tes and S groups (P > 0.01); its value was higher than in the Tes+Tac and Tac groups (P < 0.01). One rat in group Tes had fatty infiltration grade II. Inflammatory cells were grade I in group Tes but fibrosis formation was grade I in group Tes+Tac. Our results show that tacrolimus and testosterone administration may shorten sciatic nerve regeneration time. Testosterone may diminish gastrocnemius muscle atrophy after sciatic nerve crush. [ABSTRACT FROM AUTHOR]

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology. [ABSTRACT FROM AUTHOR]