Scientists have uncovered the role of immunoglobulin G in body aging

Recently, the teams of Liu Guanghui of the CAS Institute of Zoology, Gu Ying of BGI Research, Zhang Weiqi of the Beijing Institute of Genomics at CAS, and Qiu Jing of the same institute provided compelling answers.

By analysing millions of spatial points in nine organs of male mice, the researchers created highly accurate maps of spatial transcriptomics. These maps showed the distribution of more than 70 cell types, providing a clear picture of how aging affects the body at the cellular level.

The transcriptome landscape created, calledGerontological Geography(GG), revealed common features of aging: structural disruption of tissues and loss of cellular identity.

This landscape is a significant step forward. We have identified the epicentres of aging in different organs and found that immunoglobulin accumulation is a key characteristic and driver of aging," said Professor Liu.

Using Organisational Structure Entropy (OSE) analysis, the team found that increased structural disorder and loss of cellular identity are universal signs of systemic ageing. This suggests that damage to the structural organisation of tissues may be a major cause of functional decline of organs with age.

The researchers also identified senescence-sensitive zones (SSS), the areas in tissues most affected by aging. Areas closer to the SSS showed higher structural entropy and greater loss of cellular identity, suggesting that these areas may be the core of organ aging.

It is particularly interesting that in immune organs, plasma cells responsible for antibody synthesis and other specialised cells are major components of the SSS microenvironment. The levels of immunoglobulin-related genes are elevated in these cells around SSS.

Further investigation revealed that immunoglobulin G (IgG) accumulates in various tissues and organs with age in humans and mice, making it a potential biomarker of aging. Moreover, IgG directly induces senescent macrophages and microglia by inducing the release of inflammatory factors. IgG administration to young mice triggered senescence in several organs, demonstrating its potent effects.

Looking forward, the team developed an intervention strategy using antisense oligonucleotides (ASOs) to reduce IgG levels in mouse tissues, which slowed organ aging.

More information: Shuai Ma et al, "Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging", Cell (2024). DOI: 10.1016/j.cell.2024.10.019

Provided to Phys.org by the Chinese Academy of Sciences