摘要: Adipose tissue serves as a crucial energy storage and metabolic organ in the human body. With the surging of elderly population in China comes significant challenges in preventing and managing age-associated diseases, while adipose tissue aging represents one of the pivotal initiating events for multi-organ senescence. To address these challenges, the Aging China Biomarkers Consortium (ABC) has established an expert consensus on biomarkers of adipose tissue aging by digesting literature and collecting insights from scientists and clinicians. This consensus provides a comprehensive evaluation of the key changes and characteristics, as well as biomarkers related to adipose tissue aging and proposes a systematic framework categorizing these biomarkers into functional, structural and humoral dimensions. Within each dimension, the ABC recommends clinically and empirically validated biomarkers and parameters for assessing both physiological and pathological changes in adipose tissue during aging, which aims to establish a foundation for future prediction, diagnosis, early warning and treatment for adipose tissue aging and its related diseases, with the ultimate goal of improving adipose tissue health and promoting healthy aging in elderly populations both in China and worldwide.

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摘要: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a primary immunodeficiency characterized by hyperactivated lymphocytes and recurrent infections. This study presents a 2.5-year-old patient with a novel PIK3CD gene mutation (c.1309C>T; p. R437C) derived from his mother. We explored the immunological consequences of this mutation in both the patient and his mother, revealing defects in T cell differentiation, B cell maturation, and mitochondrial function. Notably, we found that the elevated CD38 expression on B cells is a key factor driving B cell senescence, mitochondrial dysfunction, and increased transitional B cell proportion, contributing to the observed immunodeficiency, such as diminished serum antibodies. Further investigations of the PI3K/AKT/mTOR pathway highlight a preferential activation of mTORC2 over mTORC1. We also demonstrate that the transcription factor FOXO1, a downstream molecule of PI3K/AKT signaling, regulates CD38 expression by binding to the promotor of the CD38 gene, linking this pathway to B cell dysfunction. This novel mutation expands the spectrum of PIK3CD mutations associated with APDS and provides new insights into the molecular mechanisms underlying B-cell senescence and other immune dysregulation. Moreover, targeting the AKT-FOXO1 axis could offer therapeutic potential to reverse B-cell dysfunction and improve immune responses in patients with PIK3CD mutations.

摘要: The visual system is essential for human perception, converting light signals into electrical impulses and transmitting them to the brain to process environmental information. As individuals age, their physiological functions gradually decline, leading to age-related vision impairment that significantly impacts the quality of life in elderly individuals. China is home to the world's largest aging population and faces significant challenges in combating visual system aging through effective treatments and interventions. In response to this challenge, the Aging Biomarker Consortium (ABC) of China has developed a consensus statement on biomarkers of visual system aging by integrating cutting-edge global research and synthesizing evidence-based medicine with clinical expertise. This consensus provides a multi-dimensional evaluation framework encompassing functional, morphological, and molecular biomarkers. Validated biomarkers for each domain are recommended not only to facilitate the early detection of vision changes but also to provide insights into the progression of age-related ocular diseases. By advancing this initiative, ABC aims to revolutionize visual health management in aging societies, ultimately improving outcomes for elderly populations in China and globally.

摘要: Mitochondrial dysfunction is a hallmark of aging, characterized by a decline in mitochondrial biogenesis and quality control, compromised membrane integrity, elevated ROS production, damaged mitochondrial DNA (mtDNA), impaired mitochondrial-nuclear crosstalk, and deregulated metabolic balance. Among the key longevity regulators, sirtuin family members SIRT3, SIRT4, and SIRT5 are predominantly localized to mitochondria and play crucial roles in maintaining mitochondrial function and homeostasis. This review explores how mitochondrial sirtuins mitigate aging-related mitochondrial dysfunctions and their broader implications in aging-related diseases. By elucidating the intricate interplay between mitochondrial dysfunction and mitochondrial sirtuins, we aim to provide insights into therapeutic strategies for promoting healthy aging and combating age-related pathologies.

摘要: Microvesicles (MVs) have convenient clinical applications and play functional roles in cellular signal transduction. Although the clinical importance of MVs is being increasingly recognized, the current diversity of isolated protocols results in a heterogeneous population of their unknown origins, even expands to uncertain functions. Here, we systematically investigated the composition of MVs at different centrifugal speed intervals and discovered that centrifugation at 3000 g is critical in determining the composition of MVs. We observed that platelet-derived particles accounted for more than 80% of MVs under 3000 g, while only about 20% of MVs were obtained over 3000 g. The discovery that more than 80% of platelet-derived MVs sheds new light on their function, including procoagulation activity and clinical diagnosis, etc. Our work not only optimizes the method for MVs isolation but also clarifies the physiological functions and characteristics that should be attributed to platelets rather than MVs. Consequently, these findings will derive new conceptualizations regarding MVs' composition and function.

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摘要: Human pluripotent stem cells (hPSCs) hold great promise in regenerative medicine. However, immune rejections remain one of the major obstacles to stem cell therapy. Though conventional immunosuppressants are available in clinics, the side effects prevent the wide application of hPSCs derivatives, compromising both survival rate and quality of life. In recent years, a myriad of strategies aimed at inducing immune tolerance specifically by engineering stem cells has been introduced to society. One strategy involves human leukocyte antigen (HLA) deletion through gene editing, affording allografts the capability to evade the host immune system. Another strategy involves immune cloak, which is the focus of this review, with emphasis on the overexpression of immune checkpoints and the blocking of immune cytotoxic pathways. Nevertheless, co-transplantation with mesenchymal stem cells (MSCs) and enhanced MSCs confers immune privilege to engraftments. This review summarizes recent studies on the intricacies of immune tolerance induction by engineering stem cells. In addition, we endeavor to deliberate upon the safety and limitations associated with this promising and potential therapeutic modality.