A new study published in iMeta has identified key gut bacterial strains and metabolic markers associated with aging and validated their potential functions, offering a fresh strategy for delaying aging and addressing age-related chronic diseases.

The study was conducted by the Biomedical Metabolomics Team at the Innovation Academy for Precision Measurement Science and Technology (APM) of the Chinese Academy of Sciences (CAS).

An imbalance in gut microbiota and host metabolic disorders are considered important factors associated with the aging process. The diversity, composition, and function of the human gut microbiota change significantly with aging, and maintaining a relatively "young" microbial community has been shown to alleviate age-related decline.

Therefore, identifying the biological signatures of gut microbiota imbalance and host metabolic disorders during aging is of great significance for understanding human longevity and guiding precise geriatric medical interventions for age-related diseases.

In the study, the research team collaborated with multiple institutions, including Hubei Provincial Hospital of Traditional Chinese Medicine, Southern Medical University, and Guangxi Alage Life Science Corporation Ltd. Over a period of more than two years, the team collected fecal samples from individuals across different age groups, including young, elderly, and centenarian populations.

Using multi-omics technologies combined with bioinformatics, they analyzed microbiota and metabolic characteristics during aging, constructed an aging microbiota and metabolism database, and identified the key gut microbial strain Clostridium scindens in centenarians and its characteristic metabolite indole-3-acetic acid (IAA). 

The researchers further elucidated the anti-aging mechanism, showing that IAA mediates the expression of intestinal tight junction protein (CLDN10) through the aryl hydrocarbon receptor (AHR), thereby regulating intestinal homeostasis.

C. scindens and its metabolites regulate intestinal homeostasis via activating the AHR-CLDN10 signaling pathway through IAA. (Image by APM)

In addition, the team found that IAA supplementation can ameliorate osteoporosis in an AHR-dependent manner. Oral administration of IAA can also activate the interaction between intestinal AHR and poly (ADP-ribose) polymerase 1 (PARP1), repair DNA damage during the aging process, and delay cellular senescence. These findings demonstrate that the endogenous small molecule IAA has potential applications in anti-aging interventions and the improvement of age-related chronic diseases.

LIN Weichuan, special research assistant at APM, ZHANG Cui, PhD candidate at APM, and LEI Hehua, associate researcher at APM, are the co-first authors of the paper. Researcher ZHANG Limin from APM, Professor CHEN Gang from Hubei University of Chinese Medicine, Professor XIE Denghui from Southern Medical University, and Dr. LUO Weifei from Guangxi Alage Life Science Corporation Ltd. are the co-corresponding authors.

This research work was funded by projects including those supported by the CAS and the Hubei Provincial Department of Science and Technology.