In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians. This consensus provides a comprehensive assessment of biomarkers associated with liver aging and presents a systematic framework to characterize these into three dimensions: functional, imaging, and humoral. For the functional domain, we highlight biomarkers associated with cholesterol metabolism and liver-related coagulation function. For the imaging domain, we note that hepatic steatosis and liver blood flow can serve as measurable biomarkers for liver aging. Finally, in the humoral domain, we pinpoint hepatokines and enzymatic alterations worthy of attention. The aim of this expert consensus is to establish a foundation for assessing the extent of liver aging and identify early signs of liver aging-related diseases, thereby improving liver health and the healthy life expectancy of the elderly population.
Psychological stress has been associated with the onset of several diseases, including osteoporosis. However, the underlying pathogenic mechanism remains unknown, and effective therapeutic strategies are still unavailable. Growing evidence suggests that the sympathetic nervous system regulates bone homeostasis and vascular function under psychological stress, as well as the coupling of osteogenesis and angiogenesis in bone development, remodeling, and regeneration. Furthermore, extracellular vesicles (EVs), particularly mesenchymal stem cell extracellular vesicles (MSC–EVs), have emerged as prospecting therapies for stimulating angiogenesis and bone regeneration. We summarize the role of sympathetic regulation in bone homeostasis and vascular function in response to psychological stress and emphasize the relationship between vessels and bone. Finally, we suggest using MSC–EVs as a promising therapeutic method for treating osteoporosis in psychological stress.
In recent years, the world has faced significant challenges with the coronavirus disease 2019 (COVID-19) pandemic, as well as other infectious diseases such as Zika and Ebola. Furthermore, the rapid rise of non-communicable diseases such as diabetes, heart disease, and cancer has placed tremendous strain on healthcare resources and systems. Unfortunately, advancements in drug development, diagnostics, and therapeutics have struggled to keep pace with the emergence and progression of diseases, necessitating the exploration of new technologies for the discovery and development of biomedicines and biotherapies. Synthetic biology, a revolutionary field in modern science, holds great promise in advancing drug development and disease treatment. This review provides a comprehensive overview of recent developments in the application of synthetic biology to medicine, with a specific focus on its role in drug discovery, drug production, and the diagnosis and treatment of various diseases.
Transmembrane protein 106B (TMEM106B), previously identified as a risk factor in frontotemporal lobar degeneration, has recently been detected to form fibrillar aggregates in the brains of patients with various neurodegenerative diseases (NDs) and normal elders. While the specifics of when and where TMEM106B fibrils accumulate in human brains, as well as their connection to aging and disease progression, remain poorly understood. Here, we identified an anti-body (NBP1-91311) that directly binds to TMEM106B fibrils extracted from the brain in vitro and to Thioflavin S-positive TMEM106B fibrillar aggregates in brain sections. We discovered that TMEM106B fibrils deposit in the human brain in an age-dependent manner. Notably, the TMEM106B fibril load in the brains of Parkinson’s disease with dementia patients was significantly higher than in age-matched elders. Additionally, we found that TMEM106B fibrils predominantly accumulate in astrocytes and neurons and do not co-localize with the pathological deposition formed by other amyloid proteins such as α-synuclein, Aβ, and Tau. Our work provides a comprehensive analysis of the burden and cellular distribution of TMEM106B fibrils in human brains, underscoring the impact of both aging and disease conditions on TMEM106B fibril deposition. This highlights the potential significance of TMEM106B fibrils in various age-related NDs.
Ovarian aging is mainly characterized by a progressive decline in oocyte quantity and quality, which ultimately leads to female infertility. Various therapies have been established to cope with ovarian aging, among which exosome-based therapy is considered a promising strategy that can benefit ovarian functions via multiple pathways. Here, we isolated and characterized exosomes derived from ovarian follicular fluid and profiled the differential expression patterns of noncoding exosomal RNAs in young and aged women. Treatment with young mouse-derived exosomes efficiently rescued ovarian function in aged mice. The follicular fluid exosomes from young mice and miR-320-3p can also promote the proliferation of ovarian granulosa cells and improve mitochondrial function from old mice in vitro. The mechanism may be involve that exosomes transfer miR-320-3p to granulosa cells, and inhibit the expression of FOXQ1. Exosomes also can increase the number of primordial and growing follicles, and improve the developmental ability of oocytes in the old mice in vivo. And hnRNPA2B1 controls miR-320-3p entry into exosomes. This work provides insights into the antiaging potential of follicular fluid-derived exosomes and the underlying molecular mechanisms, which may facilitate prevention of ovarian aging and an improvement in female fertility.