Chinese Scientists Unveil Aging Mechanisms Linked to Immunoglobulins

Chinese Scientists Unveil Aging Mechanisms Linked to Immunoglobulins

Beijing, November 5, 2024 - A groundbreaking study from the Chinese Academy of Sciences (CAS) and BGI Research has shed new light on the aging process, revealing how immunoglobulins play a dual role in systemic aging. Published in the prestigious journal Cell on November 4, the research could potentially alter our understanding of aging and its associated diseases.

The collaborative effort, involving teams from CAS's Institute of Zoology, Beijing Institute of Genomics, and BGI Research, has developed high-precision spatial transcriptomic maps of aging across nine organs in male mice. This detailed mapping, known as Gerontological Geography (GG), illustrates the spatial distribution of over 70 cell types, highlighting tissue structural disorder and loss of cellular identity as key aging hallmarks.

Professor Liu Guanghui, one of the study's corresponding authors, emphasized the significance of the findings: "This landscape is a significant step forward, pinpointing the epicenters of aging within multiple organs and uncovering the accumulation of immunoglobulins as a key aging characteristic and driver."

The study utilized a novel method called organizational structure entropy (OSE) analysis, which revealed that increased spatial structural disorder and loss of cellular identity are universal signs of systemic aging. This suggests that damage to spatial structure might be a primary cause of organ functional decline during aging.

Further, the researchers identified what they termed 'senescence-sensitive spots' (SSS), areas within tissues that are more prone to aging effects. These spots are characterized by higher tissue structural entropy and greater loss of cellular identity, indicating they might serve as the nucleus of organ aging.

In immune organs, plasma cells and other cells with specific functions were found to be the main components of the SSS microenvironment. The study highlighted that immunoglobulin G (IgG) not only accumulates in various tissues and organs during aging but also directly induces aging in human and mouse macrophages and microglia, promoting inflammation.

In an experimental approach, the team injected IgG into young mice, which accelerated aging in multiple tissues, confirming IgG's potent aging effects. Conversely, they developed an intervention using antisense oligonucleotides (ASO) to reduce IgG levels in mouse tissues, which delayed aging in multiple organs.

This pioneering research is the first to map the spatial transcriptome of aging across different organs in mammals, pinpointing the critical role of immunoglobulins in aging. The proposed Immunoglobulin-associated Senescence Phenotype (IASP) expands the boundaries of aging science, suggesting new pathways for interventions that could delay aging and prevent age-related diseases.

For more details on this study, please refer to Cell, DOI: 10.1016/j.cell.2024.10.019.

Contact:

Science Communication Office

Chinese Academy of Sciences

Email: science@cas.ac.cn

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