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Cell:刘光慧/张维绮/曲静/杨家印等绘制人体衰老蛋白导航图,揭示人类衰老轨迹与特征
生物世界·2025-07-25 14:36

Core Viewpoint - The article discusses a groundbreaking study that constructs a comprehensive human proteome aging map across a 50-year lifespan, revealing critical insights into the molecular mechanisms of aging and potential intervention targets [3][4][19]. Group 1: Research Findings - The study integrates ultra-sensitive mass spectrometry and machine learning to create a dynamic landscape of protein aging across seven physiological systems and 13 key tissues [4]. - It identifies protein information disruption as a core feature of organ aging, highlighting the role of mRNA-protein decoupling and pathological amyloid deposition in the systemic collapse of proteostasis networks [7]. - The vascular system is established as a "pioneer organ" in the aging process, significantly deviating from homeostatic trajectories early in life [7]. Group 2: Molecular Characterization of Aging - The research confirms that aging is accompanied by systemic proteostasis imbalance, characterized by a breakdown of the central dogma information flow, leading to impaired conversion of genetic information into functional proteins [9]. - Key findings include widespread accumulation of pathological proteins, forming an inflammatory aging network, which serves as a molecular basis for inflammaging [9][10]. Group 3: Aging Milestones and Mechanisms - The study identifies around 30 years of age as a critical inflection point for aging trajectories, with adrenal tissues showing early aging characteristics [12]. - A significant biological transition occurs between 45-55 years, where most organ proteomes experience a "molecular cascade storm," marking a key window for systemic aging acceleration [12][21]. Group 4: Vascular Aging Mechanisms - The research validates the "vascular aging hub" hypothesis, demonstrating that specific senescence-associated secretory factors, such as GAS6, drive endothelial and smooth muscle cell aging [15][16]. - Evidence supports the theory of "aging diffusion," where local aging tissues influence distant organs through specific secretory factors [16]. Group 5: Implications for Aging Research and Interventions - The study proposes a new framework for systemic aging research, moving beyond single-tissue models to a multi-organ interaction network [19]. - It introduces a novel tool for precise aging assessment through the development of organ-specific "proteome aging clocks," enabling non-invasive evaluation of biological age [20]. - Key intervention targets are identified, including factors mediating inter-organ signaling and common biomarkers, with the 45-55 age range highlighted as a critical intervention window [21]. - The findings pave the way for proactive aging disease prevention strategies, shifting from reactive treatment to early intervention based on molecular aging clocks [23]. Group 6: Methodological Innovations - The research successfully combines ultra-sensitive mass spectrometry, AI modeling, and multi-scale omics analysis to create a comprehensive framework for studying aging [24]. - This methodological advancement enhances the understanding of human aging and accelerates the translation of life sciences technologies into clinical applications [24].