Cell cycle arrest, senescence-associated secretory phenotypes, metabolic dysregulation, and macromolecular damage are all characteristics of cellular senescence, which is a permanent state that can be brought on by various stress signals throughout the life cycle. These non-proliferating cells occupy key cellular niches and elaborate pro-inflammatory cytokines, contributing to aging-related diseases and morbidity, including musculoskeletal system disorder, neurodegenerative disease, and cancer. Despite some controversy, many new targets and signaling pathways related to the regulation of cellular senescence have been identified in the last decade, focusing on epigenetic changes and immune system activation.
DNA methylation in human peripheral blood and tissues, also known as the "epigenetic clock," has been shown to be a better predictor of actual senescent levels than transcriptomic or proteomic data or telomere length. Expression of "Yamanaka factors," such as Oct4, to restore pluripotency in differentiated cells relies on loosening heterochromatin and reducing overall levels of the repressive histones H3K9me2, H3K9me3, and 5-methylcytosine, thereby eliminating the epigenetic memory of differentiated cells. In conclusion, epigenetic regulation, including (de-) methylation, (de-) acetylation, miRNAs, and histone/DNA modification changes, is an important driver of cellular senescence.
A comparison of genes from young and old tissues from mice, rats, and humans showed that age-related changes in gene expression were most significantly involved in the induction of inflammatory and immune response genes, suggesting that aberrant activation of the immune system is a common hallmark of senescent tissues. Oxidative stress, pro-inflammatory cytokines, DNA damage, organelle dysfunction, defective autophagy, and stem cell aging are all involved in regulating inflammation at the transcriptional and post-transcriptional levels and have now been partially elucidated as sources and mechanisms of inflammation in aging tissues. In addition, a chronic state of low-grade inflammation is associated with the pathogenesis of many age-related diseases (cancer, atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes).
Therefore, the unveiling of the epigenetic and immune regulation network will help us to understand the mechanisms of senescence better and develop therapeutical strategies to address aging-associated diseases. The focus of this issue is on the dual and, at first seems contradictory roles that cellular senescence plays in the emergence of complex disorders, with a particular focus on cancer, musculoskeletal disease, and Alzheimer's disease. We encourage contributions to this topic in the form of original research articles, reviews, practice guides, or opinion pieces that include, but are not limited to:
• Epigenetic networks that contribute to the pathogenesis, progression, and therapeutic progression of senescence at the population, animal model, and cellular levels.
• Recent advances in the relationship between immune responses and cellular senescence to aid understanding of the immune system's role in senescence, as well as to explore future research directions and how to facilitate clinical translation to the treatment of cancer, musculoskeletal disease, and Alzheimer's disease.
• Development of new biomarkers or identification of subtypes related to cellular senescence.
• Application of methods related to the removal of senescent cells in the treatment of cancer, musculoskeletal disease, and Alzheimer's disease.
• Crosstalk of cellular senescence and the immune system in musculoskeletal disorders.
• Relationship between abnormal neurotransmitters and neuropeptides with cellular senescence in neuroinflammation.
Cell cycle arrest, senescence-associated secretory phenotypes, metabolic dysregulation, and macromolecular damage are all characteristics of cellular senescence, which is a permanent state that can be brought on by various stress signals throughout the life cycle. These non-proliferating cells occupy key cellular niches and elaborate pro-inflammatory cytokines, contributing to aging-related diseases and morbidity, including musculoskeletal system disorder, neurodegenerative disease, and cancer. Despite some controversy, many new targets and signaling pathways related to the regulation of cellular senescence have been identified in the last decade, focusing on epigenetic changes and immune system activation.
DNA methylation in human peripheral blood and tissues, also known as the "epigenetic clock," has been shown to be a better predictor of actual senescent levels than transcriptomic or proteomic data or telomere length. Expression of "Yamanaka factors," such as Oct4, to restore pluripotency in differentiated cells relies on loosening heterochromatin and reducing overall levels of the repressive histones H3K9me2, H3K9me3, and 5-methylcytosine, thereby eliminating the epigenetic memory of differentiated cells. In conclusion, epigenetic regulation, including (de-) methylation, (de-) acetylation, miRNAs, and histone/DNA modification changes, is an important driver of cellular senescence.
A comparison of genes from young and old tissues from mice, rats, and humans showed that age-related changes in gene expression were most significantly involved in the induction of inflammatory and immune response genes, suggesting that aberrant activation of the immune system is a common hallmark of senescent tissues. Oxidative stress, pro-inflammatory cytokines, DNA damage, organelle dysfunction, defective autophagy, and stem cell aging are all involved in regulating inflammation at the transcriptional and post-transcriptional levels and have now been partially elucidated as sources and mechanisms of inflammation in aging tissues. In addition, a chronic state of low-grade inflammation is associated with the pathogenesis of many age-related diseases (cancer, atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes).
Therefore, the unveiling of the epigenetic and immune regulation network will help us to understand the mechanisms of senescence better and develop therapeutical strategies to address aging-associated diseases. The focus of this issue is on the dual and, at first seems contradictory roles that cellular senescence plays in the emergence of complex disorders, with a particular focus on cancer, musculoskeletal disease, and Alzheimer's disease. We encourage contributions to this topic in the form of original research articles, reviews, practice guides, or opinion pieces that include, but are not limited to:
• Epigenetic networks that contribute to the pathogenesis, progression, and therapeutic progression of senescence at the population, animal model, and cellular levels.
• Recent advances in the relationship between immune responses and cellular senescence to aid understanding of the immune system's role in senescence, as well as to explore future research directions and how to facilitate clinical translation to the treatment of cancer, musculoskeletal disease, and Alzheimer's disease.
• Development of new biomarkers or identification of subtypes related to cellular senescence.
• Application of methods related to the removal of senescent cells in the treatment of cancer, musculoskeletal disease, and Alzheimer's disease.
• Crosstalk of cellular senescence and the immune system in musculoskeletal disorders.
• Relationship between abnormal neurotransmitters and neuropeptides with cellular senescence in neuroinflammation.
