Identification of fecal microbiome signatures associated with familial longevity and candidate metabolites for healthy aging

Author:

Gong Junli1234ORCID,Liu Sanxin5,Wang Shisi5,Ruan Hengfang5,Mou Qianqian6,Fan Ping5,Chen Tao7,Cai Wei5,Lu Yongjun46ORCID,Lu Zhengqi5ORCID

Affiliation:

1. Department of Colorectal Surgery, The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong China

2. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong China

3. Guangdong Institute of Gastroenterology Guangzhou Guangdong China

4. Key Laboratory of Human Microbiome and Elderly Chronic Diseases Ministry of Education Guangzhou Guangdong China

5. Department of Neurology, Psychological and Neurological Diseases Research Centre The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou Guangdong China

6. Run Ze Laboratory for Gastrointestinal Microbiome Study School of Life Sciences of Sun Yat‐sen University Guangzhou Guangdong China

7. South China Institute of Biomedicine Guangzhou Guangdong China

Abstract

AbstractGut microbiota associated with longevity plays an important role in the adaptation to damaging stimuli accumulated during the aging process. The mechanism by which the longevity‐associated microbiota protects the senescent host remains unclear, while the metabolites of the gut bacteria are of particular interest. Here, an integrated analysis of untargeted metabolomics and 16S rRNA gene sequencing was used to characterize the metabolite and microbiota profiles of long‐lived individuals (aged ≥90 years) in comparison to old‐elderly (aged 75–89 years), young‐elderly (aged 60–74 years), and young to middle‐aged (aged ≤59 years) individuals. This novel study constructed both metabolite and microbiota trajectories across aging in populations from Jiaoling county (the seventh longevity town of the world) in China. We found that the long‐lived group exhibited remarkably differential metabolomic signatures, highlighting the existence of metabolic heterogeneity with aging. Importantly, we also discovered that long‐lived individuals from the familial longevity cohort harbored a microbiome distinguished from that of the general population. Specifically, we identified that the levels of a candidate metabolite, pinane thromboxane A2 (PTA2), which is positively associated with aging, were consistently higher in individuals with familial longevity and their younger descendants than in those of the general population. Furtherly, functional analysis revealed that PTA2 potentiated the efficiency of microglial phagocytosis of β‐amyloid 40 and enhanced an anti‐inflammatory phenotype, indicating a protective role of PTA2 toward host health. Collectively, our results improve the understanding of the role of the gut microbiome in longevity and may facilitate the development of strategies for healthy aging.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Cell Biology,Aging

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