Myosin binding protein-C (MyBP-C) comprises a family of muscle accessory proteins that function in organizing and maintaining sarcomeric structure and regulating contractile function and actomyosin crossbridge cycling. Mutations in MYBPC1, the gene encoding the slow skeletal isoform (sMyBP-C), lead to a novel dominant form of myopathy termed Myotrem (OMIM: 318524) characterized by muscle weakness, congenital hypotonia, skeletal deformities, and characteristic tremor affecting the extremities and tongue. Due to the restricted expression of MYBPC1 to skeletal muscle, as well as the absence of neuropathy in these patients, this tremor is believed to be a novel entity originating within the muscle itself. To further investigate Myotrem, our group has developed a murine model harboring a knock-in (KI) MYBPC1 E248K mutation that faithfully recapitulates disease phenotype. Subsequent studies in KI muscle revealed that structural alterations of the sarcomere underlie the myopathy and are integral to pathogenesis. In human patients, Myotrem manifestations progress through childhood until adolescence, at which the phenotype stabilizes with no further deterioration. However, the clinical manifestation of Myotrem after mid-adulthood in response to the biological processes of aging is not known. In these studies, we used the murine KI model to perform in vivo contractile force measurements and quantitative structural analysis of immunofluorescence-stained muscle to extensively characterize muscle structure and function in mid- and late-adulthood. We show that this stabilization period expires in late adulthood as KI mice show a decline in muscle structure and function in a sex- and muscle-specific manner where males and larger muscle muscles are more affected. Furthermore, although Myotrem tremorgenesis is considered to originate intrinsically in the muscle, the molecular mechanism is largely unknown. Notably, we found that permeabilized soleus fibers from KI mice exhibited unsolicited pulse activity with unprecedented regularity and persistence. Immunoblot and mechanical step-stretch experiments reveal that these pulsing KI fibers are slow-twitch in nature and display enhanced stretch activation properties. We posit that these pulsing fibers function as a myogenic pacemaker for tremor. Collectively, these studies provide essential information to inform patients afflicted with Myotrem of disease development and provide putative mechanisms for pathologic myogenic tremorgenesis.