In daily life, we often hear that the elderly will complain that their health is not as good as before, they are easily fatigued, their memory is reduced, and even various chronic diseases occur. What is the scientific rationale behind these phenomena?

Over time, aging leads to unbalanced changes in the structure and properties of cells within tissues, disrupting the molecular regulatory network within cells, and affecting the spatial distribution and interaction of cells within organs. At present, scientists have limited understanding of how aging triggers tissue and cell degeneration at the spatial level, and revealing the core driving forces of aging in the complex spatio-temporal context is a challenge for aging science research.

Recently, Liu Guanghui's research group and Qu Jing's research group from the Institute of Zoology of the Chinese Academy of Sciences, Zhang Weiqi's research group from the Beijing Institute of Genomics (National Bioinformatics Center) and Gu Ying's team from the BGI Life Science Research Institute constructed a high-precision Gerontological Geography (GG) for the first time, revealing that tissue structure disorder and loss of cell identity are common characteristics of multi-organ aging, and accurately locating the core areas of aging in multiple organs. The accumulation of immunoglobulins was found to be a key feature and driving factor of aging, which laid a new scientific foundation for the analysis of the mechanism, early warning and intervention of aging. The findings were published in the journal Cell on 4/0.

In this study, a high-precision spatial map of aging of 70 tissues and organs of mice, namely hippocampus, spinal cord, heart, lung, liver, small intestine, spleen, lymph nodes and testis, was constructed through the fine analysis of millions of spatial loci, revealing the distribution characteristics of more than 0 cell types. Through the development of a new method of spatial tissue structure entropy analysis, this study evaluated the changes in the degree of tissue and organ structure chaos during aging, and found that spatial structure disorder and loss of cell identity across tissues and organs are common characteristics of systemic aging.

For example, aging can lead to structural damage to the white pulp limb zone of the spleen, atrophy of the lymphocyte pool, and disruption of the spatial structure of liver cells. These tissue spatial structural variations may be important triggers for organ function decline.

Spatial transcriptome mapping reveals immunoglobulin-associated senescence phenotypes

Not only that, but this research also expands our understanding of the science of aging. During human and mouse aging, IgG proteins accumulate in multiple tissues and organs, suggesting that elevated IgG levels can be used as a new biomarker of aging. Studies have confirmed that IgG can directly cause macrophages and microglia senescence and release inflammatory factors in humans and mice. However, the direct injection of IgG into young mice can induce the aging of multiple tissues and organs throughout the body. Furthermore, this study developed an intervention strategy based on antisense oligonucleotides to reduce IgG content in mouse tissues and delay multi-organ aging.

This study mapped the spatial transcriptome of mammalian multi-organ aging, revealed that tissue structural disorders and loss of cellular identity are key features of aging, and localized the sensitive core region of aging. At the same time, the immunoglobulin-related senescence phenotype proposed in this study expands the research frontier of aging science and opens up a new path for delaying aging and preventing and treating related diseases. (Reporter Xiao Chunfang)