以下文章来源于肥胖世界ObesityWorld ，作者肥胖世界 肥胖的危害众所周知，而减重能直接逆转肥胖引发的代谢紊乱和心血管疾病。虽然减重最直接影响的是脂肪组织，但令人惊讶的是，科学界对 减重前后脂肪组织的微观变化知之甚少。 这一认知盲区源于两大挑战：首先，脂肪组织结构极其复杂，除脂肪细胞外，还包含免疫细胞、血管系统和基质细胞，它们杂乱无章地混合在 一起，不像其他器官那样井然有序；其次，脂肪细胞体积庞大，常常遮挡邻近细胞，使得获取精确的单细胞分辨率测序数据异常困难。 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 总体而言，这项研究证明减重通过抑制脂肪组织衰老及相关炎症和组织损伤机制，促进了代谢健康的全面改善。研究建立的减重手术后人类脂 肪组织空间数据集，将为我们理解体重减轻的生物学机制提供更加动态和深入的认知。 近日，《自然》杂志刊发了一项突破性研究，来自伦敦帝国理工学院的科学家们分析了70名受试者的惊人17万余个细胞，首次构建了减肥手术 后人类脂肪组织的单核空间 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 间充质基质/干细胞 （MSC） 因其自我更新能力和多向分化潜能，在维持体内平衡和促进组织修复方面发挥着关键作用。然而， 衰老会 损害 MSC 的功能和再 生能力，减少骨和软骨的形成，并导致诸如骨质疏松症等年龄相关疾病。 线粒体 作为参与能量代谢的重要细胞器，是衰老过程中的关键因素；线粒体功能障碍是 MSC 的显著特征 。衰老的 MSC 表现出线粒体稳态失调，包括线粒体自 噬受损、功能失调的线粒体积聚、分裂减少以及巨大线粒体形成，最终激活衰老相关通路。 值得注意的是， 能量限制 （ Energy Restriction ） 已被证明与衰老 MSC 的恢复活力、延缓年龄相关疾病以及延长物种寿命密切相关。调控线粒体 ATP 合酶的 功能对于改善线粒体功能障碍和缓解 MSC 的衰老状态至关重要，因为由此产生的能量限制状态已被证会通过促进线粒体分裂并激活线粒体自噬来清除受损线粒 体，最终减轻衰老对慢性疾病的影响。 能量限制与细胞衰老和物种寿命密切相关。 在这项最新研究中，研究团队基于能量生成的关键酶—— ATP 合酶 的结构和功能 ，开发了一种 参与能量代谢的纳米药物 （ Ene ...

Core Insights - The article discusses a significant research study published in Nature Microbiology, which reveals the mechanisms behind lung damage in patients with a history of Mycobacterium tuberculosis infection [2][7]. Group 1: Research Findings - The research team constructed the first high-precision cellular molecular network of lung tissue post-tuberculosis infection, identifying cellular senescence and inflammation as key pathological features of lung damage [2][6]. - A total of 19 post-tuberculosis lung tissue samples and 13 matched normal lung samples were analyzed using single-cell transcriptomics, focusing on the lesions and surrounding areas [5]. - The study identified molecular characteristics associated with tuberculosis, including gene expression patterns related to senescence, inflammation, fibrosis, and apoptosis [6]. Group 2: Mechanisms and Implications - The research highlighted that exacerbated vascular inflammation is a critical feature of lung tissue following tuberculosis [6]. - The team discovered that silencing FOXO3 and treating with thrombin exacerbated endothelial cell senescence and inflammation, confirming the role of FOXO3 signaling and NF-κB-dependent thrombo-inflammatory processes [6]. - These findings provide new insights into the mechanisms of tuberculosis-related lung damage and suggest potential therapeutic targets to alleviate lung injury in affected patients [7].

Core Insights - Ovarian aging is a significant process affecting women's overall health, leading to accelerated bodily decline and chronic diseases [2][6] - Recent advancements in regenerative medicine, particularly with placental peptides, offer new strategies to delay ovarian aging at the cellular level [1][9] Group 1: Ovarian Aging and Its Implications - Ovarian aging is not as visibly apparent as skin aging but has profound effects on bodily functions and can lead to chronic diseases [2] - Research indicates that aging ovarian cells exhibit increased senescence signaling pathways, with specific markers like CDKN1A/p21 showing elevated expression in older populations [5][6] Group 2: Regenerative Medicine and Interventions - The modern aesthetic medicine industry is shifting its focus from external modifications to internal nourishment, utilizing placental peptides to activate cellular self-healing and enhance ovarian health [7][9] - Placental peptides contain over 400 active cell factors that nourish ovarian cells, regulate the AKT signaling pathway, and improve hormonal balance, potentially restoring ovarian function to a youthful state [9] Group 3: Research Findings and Future Directions - Researchers have categorized ovarian granulosa cells into three subtypes based on their spatial distribution, indicating a shift in functional characteristics during ovarian aging [8] - The introduction of placental peptides as a NMPA-approved intravenous product marks a significant advancement in the field, offering a more effective delivery method with nearly 100% bioavailability [9]

Core Viewpoint - The article discusses the advancements in in vivo CAR-T cell therapy, particularly focusing on a new type of lipid nanoparticle (LNP) that does not require antibody modification, which enhances the delivery of circRNA-based CAR-T cells for treating inflammatory aging diseases [1][2][3][5]. Group 1: In Vivo CAR-T Therapy Advantages - In vivo CAR-T therapy, based on mRNA, offers significant advantages over traditional ex vivo CAR-T therapy, especially in treating inflammatory aging diseases [6][14]. - The transient expression of in vivo CAR-T cells may be beneficial for inflammatory aging, contrasting with its potential drawbacks in solid tumor treatments [6][14]. Group 2: Research Innovations - The research team developed a novel type of LNP inspired by cardiolipin, which enhances T cell targeting without the need for antibody modification [8][15]. - The study demonstrated that the CAMP lipid increases the stiffness and phase separation of LNPs, improving T cell uptake [9][15]. Group 3: CircRNA Utilization - The research utilized circRNA to modify CAR mRNA, enhancing its stability and reducing cytotoxicity, which prolongs CAR protein expression in vivo [10][15]. - The encapsulation of CAR mRNA targeting uPAR in PL40-LNP provides a proof of concept for treating liver fibrosis and rheumatoid arthritis [11][12]. Group 4: Clinical Implications - The study highlights the potential of non-antibody targeting strategies in developing in vivo CAR-T therapies for clearing senescent cells associated with inflammatory aging diseases [17].

Core Viewpoint - The study highlights the role of senescent macrophages in inducing ferroptosis in skeletal muscle, which accelerates muscle atrophy related to osteoarthritis (OA) [3][8][10]. Group 1: Osteoarthritis and Muscle Atrophy - Osteoarthritis (OA) is characterized by pathological changes including cartilage damage, subchondral bone remodeling, and synovial inflammation, with muscle atrophy being a common manifestation [2]. - Muscle atrophy associated with OA is strongly correlated with knee joint symptoms and the deterioration of joint pathology [2]. Group 2: Mechanisms of Muscle Atrophy - Senescent macrophages induce ferroptosis in skeletal muscle, leading to quadriceps atrophy associated with OA [3][8]. - The mechanism involves iron overload in senescent macrophages causing mitochondrial damage in muscle cells, which reduces aspartate metabolites and inhibits the mTORC1-HMGCR signaling pathway, ultimately decreasing endogenous coenzyme Q10 (CoQ10) synthesis [3][10]. Group 3: Role of CoQ10 - CoQ10 is crucial for maintaining muscle integrity and quality, with its levels positively correlating with antioxidant capacity, muscle mass, strength, and endurance in OA patients [6]. - Exogenous supplementation of CoQ10 has been shown to alleviate muscle atrophy by inhibiting ferroptosis, significantly increasing quadriceps mass and reducing pathological damage to OA joints [10].

Core Viewpoint - The article discusses the development of a human universal senescence index (hUSI) that accurately predicts cellular senescence across various conditions, addressing the challenges of identifying heterogeneous senescent cells [3][7][9]. Group 1: Background on Cellular Senescence - Cellular senescence (CS) is characterized by irreversible cell cycle arrest and is considered a key factor in age-related diseases [2]. - Senescent cells secrete pro-inflammatory proteins and other paracrine factors, which can stimulate immune responses and intercellular communication, leading to diverse effects in various tissues [2]. Group 2: Development of hUSI - The research team from Fudan University developed hUSI, a transcriptome-based index for assessing cellular senescence reliably across different cell types and conditions [3][7]. - The study compiled and standardized single-cell transcriptome sequencing data from 73 published studies, resulting in a comprehensive dataset of 770 senescent and non-senescent cell samples covering 34 cell types and 13 senescence types [3][9]. Group 3: Significance and Applications of hUSI - hUSI demonstrates a strong correlation with senescence phenotypes and shows robustness in predicting senescence states [9]. - The technology has identified potential senescence regulatory factors and mapped the accumulation of senescent cells in different cell types during COVID-19, as well as decoded the heterogeneous senescence states in melanoma tumors [9][10]. - The hUSI method has broad applications in aging research and clinical practice, with an open-source software package and user guide available for further use [10].

Core Viewpoint - Cellular senescence is a stable state of growth arrest closely related to age-related diseases and cancer development, characterized by an intrinsic anti-apoptotic ability and a unique secretory phenotype known as the senescence-associated secretory phenotype (SASP) [1][2]. Group 1 - Senescent tumor cells release mitochondrial DNA (mtDNA), which enhances immunosuppression mediated by polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) through the cGAS-STING pathway [3][9]. - The release of mtDNA from senescent cells can exacerbate inflammation associated with tissue damage or disease progression, indicating a potential mechanism linking cellular senescence to age-related diseases and cancer [2][6]. - The study highlights that targeting the release of mtDNA could reprogram the immunosuppressive tumor microenvironment, thereby improving cancer treatment outcomes for patients undergoing chemotherapy [9][10]. Group 2 - The research team found that both naturally senescent primary cells and tumor cells undergoing senescence due to treatment actively release mtDNA into the extracellular environment [5][7]. - Extracellular mtDNA is encapsulated in extracellular vesicles and selectively transferred to PMN-MDSC, enhancing their immunosuppressive activity through the cGAS-STING-NF-κB signaling pathway [5][10]. - Pharmacological inhibition of voltage-dependent anion channels (VDAC) can reduce extracellular mtDNA levels and reverse PMN-MDSC-driven immunosuppression, improving chemotherapy efficacy in prostate cancer mouse models [6][10].