华熙生物董事长赵燕在《钱道》访谈中表示："女人有'三怕'，一个是怕老，一个是怕丑，一个是怕 死。随着生命科学的发展，这三个方面都是能够去有效地控制的。" 谈及衰老，她表示"每个人对衰老都有担忧，但是我不害怕"。她认为真正的衰老从细胞层面开始，"由 于工作的压力，或者生活中的不顺心，这些都会影响细胞生存的环境，改变细胞信息的传递，导致混 乱。那一刻，你会觉得'哪哪都不对劲'，这其实就是衰老的开始。" 关于医美，她表示："医美说到底，它让你重拾自信，尤其对于女性，你就看到了自己不是说随着时间 的推移，我慢慢地老去，我能够掌控自己，能够很优雅地去变老。" 由@新浪财经、微博联合打造，@微博财经 #达芬奇live# 出品的对话栏目#钱道# 第一期，邀请华熙生 物董事长赵燕，与英才元投资管理有限公司董事长@宋立新 在15分钟精华对话中，坦诚分享如何识别 组织衰老、推动认知对齐、重建执行逻辑。#透过财经看世界# 新浪声明：所有会议实录均为现场速记整理，未经演讲者审阅，新浪网登载此文出于传递更多信息之目 的，并不意味着赞同其观点或证实其描述。 专题：《钱道》：对话上市公司掌门人 专题：《钱道》：对话上市公司掌门人 华熙生物 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 细胞衰老 （ Cellular senescence ） 通常被定义为一种细胞状态，其特征是在没有细胞死亡的情况下细胞周期永久性停滞。衰老细胞表现出几个典型的特征，包 括停止分裂状态、细胞形态改变、线粒体功能障碍、活性氧 （ROS） 水平升高、DNA 损伤和突变率增加以及衰老相关分泌表型 （SASP） 。 细胞衰老会影响人一生中的大脑健康和疾病；因此，研究人员正在努力识别包括大脑组织在内的各种人体组织中衰老细胞特有的基因和蛋白质表达模式。例如， 衰老在发育过程中发挥着重要作用，尤其是在诸如神经管闭合等对大脑结构正常形成至关重要的过程中。相反，在正常衰老过程中，大脑组织中衰老细胞的比例 逐渐增加。在病理学背景下， 细胞衰老 与年龄相关的 神经退行性疾病 有关，包括阿尔茨海默病 （AD） 和帕金森病 （PD） ，而在发育过程中，衰老通路的异 常激活或激活时机不当，可能在神经发育异常中发挥致病作用。因此，弄清楚衰老细胞如何在人的一生中影响大脑健康和疾病，至关重要。 2026 年 1 月 22 日， 西奈山伊坎医学院的研究人员在国际顶尖学术期刊 Cell 上发表了题为： Est ...

Core Insights - The research published by the team from Mount Sinai's Icahn School of Medicine establishes a direct link between cellular aging and brain structure, providing new perspectives on brain development, aging, and neurodegenerative diseases [1][3]. Group 1: Research Findings - Understanding brain structure is a core challenge in neuroscience, with its changes throughout life closely related to aging and neurodegenerative diseases such as Parkinson's and Alzheimer's [3]. - The study combines biopsy samples from the prefrontal cortex obtained during deep brain stimulation surgery with brain imaging data, allowing for simultaneous analysis of molecular features and brain structure in the same individual [3]. - A novel method was developed to identify aging cells in live human brain tissue, exploring the relationship between aging-related gene expression and brain structure [3][4]. Group 2: Key Discoveries - One significant finding is that the impact of cellular aging on brain structure varies by cell type and life stage; genes related to the aging of microglia are associated with larger brain volume, while those related to excitatory neurons are linked to reduced brain volume during aging [4]. - Aging-related characteristics of excitatory neurons are evident early in life, indicating that the aging process begins shortly after embryonic development [4]. - The study also detected signs of aging during developmental stages, suggesting that this process may play a critical role in early brain development [4].

Core Viewpoint - Cellular senescence is a phenomenon characterized by growth arrest, impacting various aspects from embryonic development to aging and diseases. Senescent cells accumulate over time, leading to chronic inflammation through the senescence-associated secretory phenotype (SASP), which can promote tumor growth and metastasis despite initially acting as a barrier to tumor development. Combining chemotherapy with senolytic drugs that selectively clear senescent cells may reduce tumor resistance and recurrence [2][6]. Group 1 - Senolytic drugs have been identified with various targets, but issues such as narrow therapeutic range, off-target toxicity, low efficacy, and limited bioavailability remain [2][6]. - The study published in Nature Aging reveals the anti-aging properties of Sticholysin I (StnI), showing its ability to effectively and specifically kill senescent cells and work synergistically with chemotherapy to induce tumor regression in mice [3][8]. Group 2 - StnI, a pore-forming toxin isolated from Caribbean anemones, binds with high affinity to specific lipids on the target cell membrane, leading to the formation of transmembrane pores that disrupt membrane integrity and cause cell death [6][7]. - The mechanism of StnIG involves the influx of sodium and calcium ions and the efflux of potassium ions, triggering a lethal cascade that results in cell death, particularly effective against senescent cells due to their membrane characteristics [7][8].

Core Insights - The article discusses the development of a CAR-T cell therapy targeting uPAR, which has shown potential in reversing and preventing aging-related defects in intestinal regeneration and health [2][3][8]. Group 1: Research Background - Intestinal stem cells (ISCs) drive the rapid regeneration of intestinal epithelial cells, but aging significantly reduces their regenerative capacity, leading to decreased intestinal function and increased permeability [6]. - There is a pressing need to develop strategies that can restore ISC function, especially given the high incidence of intestinal diseases in the elderly [6]. Group 2: uPAR and Aging - Previous studies have linked the expression of uPAR to aging and various conditions such as liver fibrosis and lung injury, but its role in intestinal biology and regeneration has not been thoroughly explored [7]. - The latest research indicates that uPAR-positive cells accumulate in aging intestines, adversely affecting ISC function [8]. Group 3: CAR-T Cell Therapy Findings - The study demonstrated that CAR-T cells targeting uPAR improved intestinal barrier function, regenerative capacity, inflammation, mucosal immunity, and gut microbiome composition in aged mice [8]. - These findings provide conceptual validation for the potential of immune-based targeted cell therapies to promote tissue regeneration in aging individuals [8].

Core Viewpoint - The article discusses the relationship between aging and the immune system, emphasizing how immune responses change with age and the potential for manipulating immune function to extend healthy lifespan [2][24]. Group 1: Aging and Immune Response - Aging leads to significant changes in immune cell function, including a bias towards myeloid output from bone marrow, accumulation of senescent T cells, and increased levels of systemic inflammatory cytokines [6][24]. - The immune system is increasingly recognized as a key regulator of systemic aging, potentially driving the aging process rather than merely responding to it [24]. Group 2: Mitochondrial Function and Immune Aging - Mitochondrial dysfunction is central to immune aging, as age-related decline in mitochondrial function weakens immune responses and promotes chronic inflammation [7][8]. - Mitochondria also play a role in systemic signaling, influencing immune responses across different tissues, which is often overlooked in current models of immune aging [7][8]. Group 3: Spaceflight as a Model for Aging - Research using spaceflight environments reveals that many immune changes observed in aging, such as increased inflammatory mediators and impaired adaptive immune responses, can also occur in microgravity [9][12]. - This suggests that spaceflight can serve as a valuable model for studying the mechanisms of immune aging [9][12]. Group 4: Vaccine Response in the Elderly - Elderly individuals typically exhibit lower antibody titers and fewer memory B cells post-vaccination, leading to impaired protective immune responses [14]. - Recent findings indicate that the germinal center response in older adults can be enhanced, paving the way for improved vaccine strategies tailored to aging populations [14]. Group 5: T Cell Changes with Age - Aging is associated with various changes in T cells, including reduced diversity in T cell receptor repertoires and a shift towards inflammatory phenotypes [15][16]. - Understanding whether these changes are adaptive or degenerative is crucial for developing therapeutic strategies targeting age-related immune dysfunction [15][16]. Group 6: Personalized Immunotherapy - The potential of immune modulation in treating diseases is significant, with a focus on how aging affects the efficacy of immunotherapies like CAR-T cell therapy [19]. - Tailoring immunotherapy strategies based on age-related changes in immune cell function could enhance treatment outcomes across different age groups [19]. Group 7: Future Directions in Aging Research - The field must transition from defining aging processes to developing interventions, including identifying biomarkers and strategies to selectively target pathological aging cells [21]. - Integrating artificial intelligence with systems immunology could provide new insights into the regulatory nodes of immune aging, potentially allowing for interventions that recalibrate immune responses to slow aging [24][21].

Core Insights - The article emphasizes the importance of understanding obesity through advanced scientific techniques, particularly single-nucleus RNA sequencing and spatial transcriptomics, which provide a detailed view of cellular changes in adipose tissue [6][7][12] Group 1: Research Findings - The study included three groups: 24 healthy individuals, and 25 obese individuals before and after weight loss surgery, revealing that weight loss surgery reduced the average BMI from 45.2 to 35.2, significantly improving fasting insulin and insulin resistance [7] - Analysis of over 170,000 cells identified more than 20 different cell states, showing a clear distinction in cellular organization between healthy and obese individuals, with a notable increase in macrophages in obese tissue [7][8] - In obese individuals, macrophages constituted 31% of adipose tissue, compared to 14% in healthy individuals, indicating a shift in immune cell dynamics [8] Group 2: Cellular Dynamics - The study identified two subtypes of lipid-associated macrophages (LAMs) in obese tissue: adaptive LAMs, which efficiently process lipids, and inflammatory LAMs, which are associated with insulin resistance [8][9] - The proportion of "stress-type" adipocytes in obese tissue was found to be 55%, which dropped to 14% post-weight loss, indicating a significant reduction in unhealthy adipocyte types [9][10] - The research linked obesity to cellular senescence, revealing that "stress-type" adipocytes express high levels of the senescence marker p21, which were largely eliminated after weight loss [10] Group 3: Implications for Treatment - The findings suggest that weight loss is not only about reducing fat but also involves a systemic cleansing of senescent cells, enhancing overall tissue health [12] - The persistence of inflammatory macrophages post-weight loss raises concerns about potential metabolic rebound, highlighting the need for preventive strategies [12] - The research provides insights into potential future treatments for obesity, focusing on targeting dysfunctional cells and signaling pathways rather than solely addressing energy balance [12]

Core Insights - The article emphasizes the importance of understanding obesity through advanced scientific techniques, particularly single-nucleus RNA sequencing and spatial transcriptomics, which provide detailed insights into cellular changes in adipose tissue [7][12]. Group 1: Research Methodology - The study involved three groups: 24 healthy individuals (LN group) and 25 obese individuals before and after weight loss surgery (OB and WL groups), allowing for both cross-sectional and longitudinal comparisons [8]. - The innovative "fat map" created through the research analyzed over 170,000 cells from 70 individuals, identifying more than 20 different cell states [8]. Group 2: Findings on Cellular Changes - Weight loss surgery significantly reduced the average Body Mass Index (BMI) from 45.2 to 35.2, with notable improvements in fasting insulin and insulin resistance [8]. - In healthy individuals, adipose tissue showed a well-organized community of cells, while in obese individuals, this balance was disrupted, particularly with an increase in macrophages and a decrease in mature adipocytes [8][9]. Group 3: Macrophage Dynamics - Macrophages in lean individuals constituted 14% of adipose tissue, while in obese individuals, this figure rose to 31%, with a notable presence of lipid-associated macrophages (LAMs) [9]. - LAMs were categorized into two subtypes: adaptive LAMs, which efficiently process lipids, and inflammatory LAMs, which are associated with insulin resistance [9]. Group 4: Adipocyte Changes - Analysis of over 44,000 mature adipocytes revealed a surge in unhealthy subtypes in obese tissue, including stress-type and fibrotic-type adipocytes, indicating functional failure of adipose tissue [10]. - Post-weight loss, the proportion of stress-type adipocytes dropped from 55% to 14%, indicating a significant reduction in stress and a potential for regeneration [10]. Group 5: Cellular Senescence - The study linked obesity to cellular senescence, identifying stress-type adipocytes as senescent cells expressing high levels of p21 [11]. - Weight loss effectively removed p21-positive senescent cells, leading to a decrease in harmful inflammatory factors, thus enhancing overall adipose tissue health [11]. Group 6: Implications for Future Treatments - The research highlights that weight loss is not just about reducing fat but also involves a systemic cleansing of senescent cells and restoration of tissue health [13]. - The findings suggest that future obesity interventions could focus on eliminating senescent cells or "re-educating" immune cells, moving beyond traditional energy balance models [13].

Core Viewpoint - The article discusses a groundbreaking study published in "Nature" that reveals how weight loss can reverse cellular aging and metabolic disorders associated with obesity, highlighting the complex changes in adipose tissue post-weight loss [5][8]. Group 1: Research Findings - A study analyzed over 170,000 cells from 25 obese patients post-weight loss surgery and 24 healthy controls, revealing significant changes in adipose tissue, including an increase in immune cell infiltration, particularly macrophages, from 14% to 31% [6]. - The study found that weight loss significantly reduced the total proportion of myeloid cells in adipose tissue to 18%, and shifted macrophage phenotypes from pro-inflammatory to a milder type, indicating improved metabolic function [6][7]. - Weight loss was shown to reverse gene regulation disruptions caused by obesity, including a significant reduction in the expression of aging markers like p21, demonstrating a strong anti-aging effect [7][8]. Group 2: Implications for Metabolic Health - The research indicates that weight loss promotes overall metabolic health by inhibiting aging and related inflammation and tissue damage mechanisms [8]. - The study establishes a spatial dataset of human adipose tissue post-weight loss, providing deeper insights into the biological mechanisms behind weight reduction and its effects on metabolism [8].

Core Viewpoint - The article discusses a groundbreaking study published in "Nature" that reveals how weight loss can reverse cellular aging and metabolic disorders associated with obesity, highlighting the complex changes in adipose tissue post-weight loss [5][8]. Group 1: Research Findings - A study analyzed over 170,000 cells from 25 obese patients post-bariatric surgery and 24 healthy controls, revealing significant changes in adipose tissue, including an increase in immune cell infiltration, particularly macrophages, from 14% to 31% [6]. - The study found that weight loss significantly reduced the total proportion of myeloid cells in adipose tissue to 18%, and the phenotype of macrophages shifted from pro-inflammatory to a milder subtype, indicating improved metabolic function [6][7]. - Weight loss also led to a dramatic change in mature adipocyte phenotype and metabolism, reducing stress and fibrosis while reactivating lipid synthesis and breakdown pathways, which enhances insulin sensitivity and overall adipocyte function [6][7]. Group 2: Implications of Weight Loss - The research indicates that weight loss can broadly reverse gene regulation disorders caused by obesity, significantly reducing the expression of aging markers like p21 and effectively inhibiting the aging process [7][8]. - The study establishes a spatial dataset of human adipose tissue post-weight loss, providing deeper insights into the biological mechanisms behind weight reduction and its effects on metabolic health [8].