The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

Imprinted genes: important regulators in development.

The imprinted genes are characterized for their allele-specific expression, which present a unique phenomenon in the epigenetic and developmental studies. The field had dramatically progress in terms of establishment, maintainance and function of imprinted genes in organ development. The imprinting was primarily discovered in neuro-transplantation studies, and thereafter focused on a few well-known imprinted cluster. With increasing application of omics techniques, more imprinted genes were screened and identified, which drawn great attentions and discussions by scientists in the field. One of wonderful example is peculiars extrapolation and debate of evolutional conservation of imprinted genes based on the data analysis of the whole genome DNA methylome and histone modification. In this review, the current research of imprinted genes in mammals were summarized from the feature of the genes, the roles in development, the mechanism of regulation, the advances of research methods, the evolution of parental relationship and the interaction between imprinted genes and environmental factors. This review will be helpful for general understanding and research approach of imprinted genes.