Aging constitutes a complex biological process that spans the entire lifespan and involves multiple tissues and organs. The assessment of aging status across different tissues presents both a critical challenge and a prerequisite for evaluating anti-aging interventions in the field of aging research. While classical biomarkers such as Cdkn2a (p16) have been widely utilized, they primarily reflect cellular senescence and demonstrate unstable expression or insensitivity in certain tissues, thus limiting their efficacy in comprehensive and systematic organ aging assessment.
To systematically identify new universal biomarkers for tissue aging, a collaborative research team led by Professor Kong Qingpeng from the Kunming Institute of Zoology, Chinese Academy of Sciences, and Professor Xiao Fuhui from the Medical School of Ningbo University constructed a multi-organ transcriptomic atlas of C57BL/6J mice across a continuous age spectrum. The study collected and analyzed transcriptomic data from 456 tissue samples spanning five age groups (1, 6, 12, 18, and 24 months), encompassing 17 vital organs and tissues including brain, heart, liver, spleen, lung, kidney, small intestine, skin, and muscle.
Through in-depth data mining and integration of published omics data, the researchers identified consistent upregulation of Ighm, Ccl8, and C4b mRNA expression levels across most tissues with advancing age. Notably, Ighm exhibited particularly prominent and robust characteristics. The Ighm gene encodes the heavy chain of immunoglobulin M (IgM). Further integration of public proteomic data and experimental validation of protein levels across multiple tissues from the same cohort confirmed that both Ighm gene expression and IgM protein levels significantly increased with aging in various mouse tissues and peripheral serum. Of particular significance, circulating IgM levels in blood showed positive correlation with overall frailty in mice and demonstrated sensitivity to various anti-aging interventions, including caloric restriction and pharmacological treatments.
This study systematically identified and proposed Ighm/IgM as a novel, stable, and highly universal biomarker for tissue/organ aging in mice. The circulating IgM levels not only reflect the aging status of certain tissues but also sensitively indicate the efficacy of anti-aging interventions, thereby providing new methodologies and approaches for non-invasive assessment of organ aging and health status.
The research findings, titled "Multi-organ transcriptomics in mice identifies immunoglobulin heavy constant mu (Ighm) as a tissue-level aging biomarker," were recently published online in the Proceedings of the National Academy of Sciences (PNAS). This study was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, the Chinese Academy of Sciences, and related projects from Yunnan Province and Kunming City.