Core Viewpoint - The article discusses the impact of negative social relationships, referred to as "Hasslers," on biological aging, highlighting that these relationships can accelerate aging and increase health risks [6][7]. Group 1: Biological Aging and Epigenetic Clocks - The development of epigenetic biomarkers, particularly DNA methylation-based clocks, has made it possible to quantify and study biological aging [4]. - Advanced epigenetic clocks, such as GrimAge and DunedinPACE, reflect aging phenotypes and health risks, allowing for better predictions of key health outcomes [5]. Group 2: Research Findings - A study published in PNAS found that having more "Hasslers" in one's social circle is associated with accelerated biological aging, with each additional "Hassler" increasing aging speed by approximately 1.5% and biological age by about 9 months [6][16]. - Nearly 30% of individuals reported having at least one "Hassler" in their core social circle [12]. - Women, daily smokers, those in poorer health, and individuals with adverse childhood experiences are more likely to have "Hasslers" in their social networks [13]. Group 3: Health Implications - The presence of "Hasslers" is linked to higher levels of inflammation, poorer self-rated health, and increased risk of multiple health conditions [17]. - "Hasslers" act as chronic psychosocial stressors, leading to elevated inflammation levels and negative impacts on health behaviors [19][21]. Group 4: Managing Social Relationships - The article emphasizes the importance of managing social ecosystems by identifying and evaluating negative relationships, setting boundaries, and strengthening supportive networks [24][26]. - Seeking professional help may be necessary for dealing with negative relationships, especially those involving family members [27].

随着 年龄增长 ，患上诸如 癌症 、 心血管疾病 以及 痴呆症 等严重疾病的风险会大幅上升。随着全球范围 内的人类老龄化，更好地理解贯穿一生的衰老过程变得愈发紧迫。 对个体 从出生到衰老相关死亡进行持续观察，可为我们带来对衰老这一动态过程的根本见解，然而，脊椎 动物的衰老时间跨度很长，往往难以对脊椎动物进行贯穿一生的持续性观察。 2026 年 3 月 12 日，"光遗传学之父"、斯坦福大学 Karl Deisseroth 教授在国际顶尖学术期刊 Science 上 发表了题为： Lifelong behavioral screen reveals an architecture of vertebrate aging 的研究论文。 该研究追踪了模式生物 非洲青鳉鱼 从青春期到死亡的整个过程，结果表明， 睡眠模式 和 活动水平 能够 预测寿命长短 ——清醒 时更活跃者相比懒散者往往活得更久，将睡眠时间限制在晚间者也比那些白天多睡 者活得更久。 这项研究提示了我们，在生命早期的行为也能预测未来寿命，在疾病出现迹象之前很久，就可能估算出衰 老的发展情况。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 在人类以及其他动物中 ...

Core Insights - The research published in Cell Metabolism reveals the functional characteristics of gut microbiota at the protein level and its association with host factors, particularly in metabolic diseases and aging [3][4][7]. Group 1: Research Findings - The study analyzed 1,967 fecal samples from 1,399 middle-aged and elderly individuals in China, identifying microbial functions related to 44 phenotypes [4][8]. - It was found that the carbon metabolism and energy production functions associated with aging are driven by species from the Bacillota, Bacteroidota, Actinomycetota, and Pseudomonadota phyla [4]. - In various metabolic diseases, a consistent reduction in proteins related to carbohydrate metabolism, energy metabolism, amino acid metabolism, and short-chain fatty acid production was observed in Bacillota species [4][8]. Group 2: Key Microbial Insights - The study identified shared drug-related features in diabetes, hypertension, and dyslipidemia [4]. - Megasphaera elsdenii was confirmed as a pivotal species in type 2 diabetes, with experimental validation showing that antidiabetic drugs can promote its growth, potentially regulating blood glucose homeostasis through butyrate production [4][7]. Group 3: Implications for Treatment - The research highlights the potential therapeutic targets for metabolic diseases and aging-related conditions by elucidating the role of gut microbiota at the protein level [7][8].

Core Viewpoint - The research published in Nature Aging highlights the role of the glycolytic metabolite phosphoenolpyruvate (PEP) in promoting healthy aging by limiting cGAS-driven inflammation, suggesting PEP as a promising intervention for aging and age-related diseases [2][3][6]. Group 1: Research Findings - PEP accumulation is defined as an evolutionarily conserved protective mechanism against aging, with external supplementation of PEP alleviating neuroinflammation and improving cognitive function in Alzheimer's disease mouse models [3][6]. - Longitudinal analyses in mice and humans show that PEP levels exhibit a biphasic change with age, initially increasing and then decreasing, where blocking PEP accumulation exacerbates inflammation and accelerates aging phenotypes [5][6]. - In elderly populations, higher levels of PEP correlate significantly with lower inflammation levels and healthier characteristics [5]. Group 2: Mechanism of Action - PEP acts as an endogenous inhibitor of the cGAS-STING inflammatory signaling pathway by competitively binding to cGAS, functioning as a "natural anti-inflammatory" produced by the body [6]. - The study provides a metabolic explanation for the occurrence of inflammation-related aging and neurodegeneration, as indicated by the dual fluctuation of PEP levels during aging [7].

Core Viewpoint - The article discusses the complex biological process of aging and highlights recent research that identifies the circadian rhythm as a potential target for anti-aging interventions, specifically through the use of 3'-deoxyadenosine (3dA) to enhance the circadian rhythm in the hypothalamic paraventricular nucleus (PVN) [3][8]. Group 1: Research Findings - A study published in the journal Cell demonstrates that optimizing the timing of 3dA administration enhances the circadian rhythm amplitude in PVN neurons, reduces aging biomarkers, and extends lifespan in male mice [4][5]. - The study reveals that 3dA can restore circadian synchronization and hormonal rhythms, including cortisol, and significantly lowers epigenetic age [5][16]. - The research identifies RUVBL2 protein in PVN neurons as a critical target for the anti-aging effects of 3dA, with its specific knockout negating the benefits of the treatment [16][17]. Group 2: Mechanisms and Implications - The study outlines a clear pathway for anti-aging: administering specific drugs at the right time enhances the biological clock amplitude in PVN, regulates downstream gene expression via proteins like RUVBL2, and ultimately reverses multiple aging markers [19][20]. - The findings suggest that enhancing the rhythmic activity of PVN neurons can combat aging, establishing it as a sufficient condition for systemic protection against aging [18]. - This research opens new avenues for "time therapy," targeting biological clocks for anti-aging treatments, potentially leading to the development of drugs aimed at RUVBL2 and personalized timing therapies [20].

Core Viewpoint - The article discusses the complexity of aging and its relationship with various age-related diseases, emphasizing the need for systemic characterization of aging cell states to identify therapeutic targets for anti-aging interventions [2][4]. Group 1: Aging and Disease - Aging is a primary risk factor for many diseases, including cancer, heart disease, and dementia, leading researchers to consider whether slowing the aging process could reduce the risk of multiple diseases simultaneously [2][6]. - The study highlights that approximately 25% of cell types change with age across 21 organs/tissues, indicating a systemic signal coordinating these changes [4][9]. Group 2: Research Findings - The research team constructed a comprehensive single-cell chromatin accessibility map covering 21 organs/tissues, three age groups, and two sexes, revealing significant age-related changes in cell types and states [4][9]. - The study identified 1.3 million cis-regulatory elements and reported aging-related population dynamics in 536 major cell types and 1,828 finer subtypes [6][7]. Group 3: Methodology and Techniques - The research utilized an optimized single-cell chromatin accessibility sequencing technique (EasySci-ATAC) to analyze over 10 million cell nuclei from various age groups, focusing on chromatin accessibility changes associated with aging [6][7]. - The findings included extensive aging-related chromatin reprogramming and sex-specific chromatin states, highlighting the interaction effects of age and sex on cellular dynamics [7][9]. Group 4: Implications and Future Directions - The study provides a framework for understanding how aging reshapes chromatin landscapes and cell compositions across multiple organs, which could inform therapeutic strategies aimed at maintaining or restoring youthful tissue states [5][9]. - An interactive website has been created to facilitate exploration of the data, which is expected to be a key reference for evaluating anti-aging interventions and understanding the interplay of chromatin remodeling, cell state transitions, and tissue physiology in aging mammals [9][10].

Core Viewpoint - The article discusses the critical role of the endoplasmic reticulum (ER) in cellular homeostasis and health aging, emphasizing its involvement in various cellular processes and signaling pathways [2][3]. Group 1: Research Findings - A study published by researchers from Vanderbilt University Medical Center in the journal Nature Aging indicates that ER remodeling is a significant feature of aging and is dependent on ER-phagy [4][5]. - The research highlights that the volume of the ER in Caenorhabditis elegans significantly decreases with age, and the morphology of the ER transitions from a rough endoplasmic reticulum structure to a tubular form, correlating with a large-scale change in the ER proteome from protein synthesis to lipid metabolism [9]. - The study identifies specific factors, including TMEM-131 and the IRE-1–XBP-1 branch of the unfolded protein response, that drive age-related ER remodeling through ER-phagy [9]. Group 2: Implications of ER Remodeling - The findings suggest that ER remodeling is an adaptive response during aging, indicating that changes in ER morphology and structure are not merely passive manifestations of functional decline but rather beneficial adaptive responses [10]. - The research also indicates that methods proven to extend lifespan observe a reduction in ER size and morphological remodeling throughout the life cycle, underscoring the importance of ER dynamics in normal aging and anti-aging interventions [10][11]. - Overall, the results point to ER-phagy and dynamic changes in the ER as significant yet underappreciated mechanisms in normal aging and interventions aimed at delaying aging [11].

Core Viewpoint - The research reveals that mitochondrial superoxide acts as a protective signal during development, regulating lipid metabolism to maintain nuclear envelope integrity and delay aging [4][10]. Group 1: Mitochondrial Superoxide and Aging - Mitochondrial superoxide is not merely a destructive molecule but serves as a key protective signal that reprograms lipid metabolism pathways to protect nuclear envelope integrity and slow down aging [4]. - The study indicates that targeting lipid peroxidation could have therapeutic potential for treating progeria and improving aging processes [4][10]. Group 2: Mechanism of Protection - The integrity of the nuclear envelope is crucial for gene expression and signal transduction, with its smoothness being a hallmark of youth; aging leads to structural damage that drives cellular dysfunction and diseases [6]. - The research demonstrates that early mitochondrial stress signals can induce superoxide production, which helps maintain a youthful nuclear envelope in model organisms like C. elegans [7][9]. - The protective effect of mitochondrial signals is time-dependent, requiring oxidative signals during development to program nuclear envelope stability for the organism's later life [7]. Group 3: Lipid Metabolism and Nuclear Envelope Stability - The study found that developmental mitochondrial superoxide signals inhibit the expression of key regulators of lipid synthesis, leading to reduced levels of polyunsaturated fatty acids (PUFAs), which are prone to lipid peroxidation [8]. - By lowering PUFA levels, mitochondrial signals prevent lipid peroxidation, thereby protecting the nuclear envelope from oxidative damage; however, supplementing with PUFAs can reverse this protective effect [8][10]. Group 4: Technological Advancements - The research team developed an AI-based nuclear envelope morphology analysis system to objectively assess subcellular structural changes, significantly enhancing data accuracy and analysis efficiency [11]. - This system aims to standardize morphological research in cell biology and is accessible to global researchers through an open website [11]. Group 5: Implications for Future Research - The findings suggest that early-life oxidative states may have lasting impacts on structural integrity during aging, highlighting lipid peroxidation as a core driver of nuclear envelope aging [11]. - The study opens avenues for developing interventions targeting lipid metabolism to delay aging and treat age-related diseases [10].

Core Insights - The recent conference in Guangzhou revealed significant findings regarding aging and its biological connections to chronic diseases, emphasizing the potential for targeted interventions in aging processes [1][3]. Group 1: Research Findings - Professor Deng Haiteng from Tsinghua University reported a breakthrough in proteomics, identifying a significant increase in the "immunoglobulin profile" in multiple organs of aging mice, indicating immune system dysregulation as a core biological feature of aging [1][3]. - The research discovered plasma protein biomarkers that can predict biological age and key intervention targets, providing new evidence for proactive health intervention strategies aimed at aging [3][6]. Group 2: Implications for Health Interventions - The findings suggest that aging itself can be a target for intervention rather than a passive outcome, offering a new scientific approach to prevent chronic diseases through anti-aging strategies [3][6]. - Researcher Huo Junsheng highlighted the shift in understanding aging from a vague concept of "damage accumulation" to precise "identification dimensions," with over ten aging markers identified, including telomere shortening and mitochondrial dysfunction, which provide clear targets for product development [6][8].

Core Viewpoint - The article discusses a groundbreaking study on protein restriction (PR) and its potential anti-aging effects, highlighting the importance of dietary interventions in extending lifespan and improving health [1][2][12]. Group 1: Research Findings - The study systematically mapped the proteomic landscape of aging across 41 organs/tissues in male mice, revealing significant protein expression heterogeneity during aging [4]. - Protein restriction was found to significantly alleviate age-related protein expression abnormalities in various tissues [6]. - The research indicated that protein restriction reduces age-related DNA methylation accumulation and reverses abnormal protein phosphorylation patterns in aging tissues [6]. Group 2: Health Implications - The study confirmed that protein restriction has cross-species cardiovascular protective effects, supported by analyses of plasma samples from both mice and humans [7]. - It was noted that lower protein intake is associated with enhanced cardiovascular health and reduced inflammation risk in humans [11]. Group 3: Timing and Gender Differences - The effects of protein restriction vary by gender and timing, with middle age identified as the optimal period for dietary intervention [8][11].