Core Viewpoint - Aging is a major risk factor for various neurodegenerative diseases, including Alzheimer's disease, and is associated with the accumulation of senescent cells that propagate the aging process through paracrine signaling [2] Group 1: Research Findings - The research published in Nature Aging demonstrates that border-associated macrophages (BAM) regulate cognitive aging by inducing paracrine senescence in microglia through migrasome-mediated mechanisms [4][8] - In the early stages of brain aging, BAM acquire senescence-related characteristics, potentially due to prolonged exposure to beta-amyloid (Aβ) [7] - Senescent-like BAM exhibit increased production of migrasomes, which transmit aging-related signals to neighboring cells, particularly microglia, inhibiting their apoptosis and promoting senescence induction [8] Group 2: Intervention Strategies - The research team developed intervention strategies targeting migrasome production by delivering siRNA to block Tspan4, which can improve cognitive deficits in aged mice [8] - These findings suggest that migrasomes are powerful carriers of aging regulatory signals and represent a promising target for Senomorphic therapies, which aim to inhibit the senescence-associated secretory phenotype without affecting cell death [8]

Core Insights - The article discusses the significant advancements in the understanding of migrasomes, a newly discovered organelle, over the past decade, highlighting their biological roles and implications in various diseases [2][3]. Summary by Sections Discovery and Characteristics of Migrasomes - In 2015, a team led by Professor Yu Li at Tsinghua University identified migrasomes in NRK cells, which are large membrane-bound structures resembling open pomegranates, crucial for cell migration [5]. - Migrasomes contain numerous internal vesicles and are rich in specific proteins, indicating their complex structure and dual role as both secretion hubs and extracellular vesicles [5][6]. Mechanisms of Biogenesis - The biogenesis of migrasomes occurs in three stages: nucleation triggered by SMS2 spots, maturation coordinated by the PIP5K1α-Rab35-integrin signaling axis, and expansion facilitated by the formation of a specialized microdomain [13]. Physiological Functions - Migrasomes participate in various physiological processes, including local secretion of signaling molecules, targeted protein and RNA transfer between adjacent cells, and maintenance of cellular homeostasis under stress [18]. Challenges in Research - Current methods for detecting and analyzing migrasomes are limited, necessitating advancements in microscopy and the development of reliable animal models for accurate labeling [19][20]. - Fundamental questions regarding the cellular origin, abundance, distribution, and dynamics of migrasomes remain unanswered, indicating a need for collaborative research efforts [21]. Implications in Disease - Migrasomes are believed to play significant roles in various diseases, particularly in immune-related conditions, suggesting potential avenues for further research [24]. - The therapeutic potential of migrasomes is highlighted, as they could serve as diagnostic tools or delivery vehicles for treatments, marking a transformative shift in the field [24].