The skeletal muscle is an important organ for movement and metabolism in human body, and its physiological aging underlies the occurrence of muscle atrophy and sarcopenia. China has the largest aging population in the world and is facing a grand challenge with how to prevent and treat skeletal muscle aging-related diseases. To address this difficult problem, the Aging Biomarker Consortium (ABC) of China has reached an expert consensus on biomarkers of skeletal muscle aging by synthesizing literatures and insights from scientists and clinicians. This consensus attempts to provide a comprehensive assessment of biomarkers associated with skeletal muscle aging, and proposes a systematic framework to classify them into three dimensions: functional, structural, and humoral. Within each dimension, the experts recommend clinically relevant biomarkers for skeletal muscle aging. This consensus aims to lay the foundation for future research on skeletal muscle aging, facilitating precise prediction, diagnosis, and treatment of skeletal muscle aging and sarcopenia. It is anticipated to make significant contributions to healthy aging of skeletal muscle in the elderly population in China and around the world as well.
Proper chromosome alignment at the spindle equator is a prerequisite for accurate chromosome segregation during cell division. However, the chromosome movement trajectories prior to alignment remain elusive. Here, we established a 4D imaging analysis framework to visualize chromosome dynamics and develop a deep-learning model for chromosome movement trajectory classification. Our data reveal that chromosomes follow at least three distinct movement trajectories (retracing, congressing, and quasi-static) to arrive at the equator. We further revealed the distinct roles of multiple kinesin superfamily proteins (KIFs) in coordinating and maintaining the chromosome movement trajectories. In summary, we have presented an efficient and unbiased approach to studying chromosome dynamics during cell division, thereby uncovering a variety of chromosome movement trajectories that precede alignment.
The heterogeneity of ovarian mesenchymal/stromal cells has just been revealed in both mice and humans. However, it remains unclear about the cellular development trace and the intercellular communication network in the whole life of the ovary. In the study, we integrated ours and published single-cell RNA sequencing data from E11.5 (embryonic day 11.5) until M12 (12-month-old) ovaries to show the dynamics of somatic cells along the developmental timeline. The intercellular crosstalk among somatic cell types was depicted with collagen signaling pathway as the most outgoing signals from stromal cells. We identified mesenchymal progenitor cells (CD24+) as the origin of stromal cells. Although their numbers decreased significantly in adults, the cells served as the major signal sender until ovarian senescence. Moreover, the ovarian injury could activate these stem cells and induce stroma remodeling in the aged ovary. Thus, mesenchymal progenitor cells may represent a new strategy to delay ovarian aging in the future.
Oxidative stress diminishes the functionality of hematopoietic stem cells (HSCs) as age advances, with heightened reactive oxygen species (ROS) levels exacerbating DNA damage, cellular senescence, and hematopoietic impairment. DDO1002, a potent inhibitor of the NRF2–KEAP1 pathway, modulates the expression of antioxidant genes. Yet, the extent to which it mitigates hematopoietic decline post-total body irradiation (TBI) or in the context of aging remains to be elucidated. Our study has elucidated the role of DDO1002 in modulating NRF2 activity, which, in turn, activates the NRF2-driven antioxidant response element (ARE) signaling cascade. This activation can diminish intracellular levels of ROS, thereby attenuating cellular senescence. In addition, DDO1002 has been demonstrated to ameliorate DNA damage and avert HSC apoptosis, underscoring its potential to mitigate hematopoietic injury precipitated by TBI. Competitive transplantation assay revealed that the administration of DDO1002 can improve the reconstitution and self-renewal capacity of HSCs in aged mice. Single-cell sequencing analysis elucidated that DDO1002 treatment attenuated intracellular inflammatory signaling pathways and mitigated ROS pathway in aged HSCs, suggesting its potential to restore the viability of these cells. Consequently, DDO1002 effectively activated the NRF2–ARE pathway, delaying cellular senescence and ameliorating impaired hematopoiesis, thereby demonstrating its potential as a therapeutic agent for age-related hematopoietic disorders.
