The authors of a recent review investigated what is known about gut microbiota in centenarians and how gut microbes can help people achieve extreme longevity [1].
What makes centenarians special?
One way of investigating what gives people longevity and health in older ages is to study people who have achieved it, especially those who have lived for a hundred years: centenarians.
It is not yet completely understood how centenarians differ from people who were unable to live so long. Many factors, including lifestyle factors and genetics, can impact whether a person can live to old age in good health, but there is still not enough understanding of what makes centenarians so special.
The authors of this review looked into a potential factor with a tremendous impact on metabolism and health: gut microbiota, the microbes that live in the human gut. They collected scientific evidence regarding these microbioes’ impact “as a potential protective factor for achieving extreme longevity.”
Inflammation and microbiota
Inflammaging, the low-grade chronic inflammation that accompanies aging, and its negative impact on health are widely known. Inflammaging also disrupts gut microbes. This review’s authors explain that such chronic inflammation creates conditions in which certain species of microbes associated with better health have difficulty growing and reproducing. Simultaneously, those conditions are favorable to microbes associated with unhealthy aging, which are known as pathobionts. Therefore, studying centenarians’ microbiota can help to answer questions about how inflammaging-protective mechanisms can develop.
Centenarians’ microbial composition
The composition of microbiota changes with age. Some microbes are lost and replaced by new microbes, which can involve potential pathobionts. This transition is a possible target for interventions.
Research done in the Blue Zones, geographical areas with a high rate of long-lived populations, demonstrated that individuals living there have gut microbiomes enriched in microbes that are considered beneficial and are linked to healthier body mass index, immunomodulation, and homeostasis [2, 3].
The authors also gathered evidence from several studies that looked at how centenarians’ microbiota differ from non-centenarians’. They noted that the microbes that were increased in the centenarians were associated with protection against inflammatory bowel disease, metabolic syndromes, obesity, and diabetes [4] along with prevention of colitis [5], liver disease [6], psychiatric disorders [7], and anxiety and depressive disorders [8]. Additionally, they possess an antitumor effect [9].
On the other hand, microbes whose levels are decreased in the centenarians possess “antioxidant and anti-inflammatory effects,” and decreased levels of one of the groups “is associated with inflammatory bowel diseases, irritable bowel syndrome, obesity, liver disorders, metabolic conditions, cancer, neurological conditions, and dermatitis” [10].
Microbial metabolites and longevity
Changes in microbiota composition are related to changes in metabolites produced by microbes. Those have also been investigated. A study on Italian centenarians revealed changes in the modifications of some lipid groups. Researchers also observed “decreased circulating levels of lipid peroxidation markers,” that is, decreased lipid deterioration by reactive oxygen species [11].
On the other hand, research also identified that some metabolites produced by microbiota can be a marker of shorter life expectancy. For example, evidence from cohorts in the United States shows that the presence of metabolic products of citric acid and bile acid metabolism is associated with a lower likelihood of reaching the age of 80 [12]. However, there is contradictory evidence from cohorts located in Bama, China, which is one of the Blue Zones. Centenarians from that cohort have high fecal short-chain fatty acids and total bile acids [13]. Untangling these seemingly contradictory results would require further investigation.
The need to expand research
The authors point that there is still very limited evidence regarding centenarians’ microbiota, which is not surprising given the diversity of the microorganisms in the human gut, “which can vary based on geographic location, lifestyles, medication, or associated diseases.” Gaining more solid data in this area can lead to the identification of therapeutic targets, allow for designing interventions to change the composition of microbes, or serve as a biomarker.
The authors suggest that future studies should investigate in more depth how microbial composition evolves through life and how it impacts the lifespan of an individual. Based on previous data on this subject, they suggest that such variables as “mode of birth, type, and quality of postnatal breastfeeding, environmental exposure, and hygienic conditions” and their role in the connection between gut microbes, longevity, and healthy aging should be investigated.
Literature
[1] Lozada-Martinez, I. D., Lozada-Martinez, L. M., & Anaya, J. M. (2024). Gut microbiota in centenarians: A potential metabolic and aging regulator in the study of extreme longevity. Aging medicine (Milton (N.S.W)), 7(3), 406–413.
[2] Wang, F., Yu, T., Huang, G., Cai, D., Liang, X., Su, H., Zhu, Z., Li, D., Yang, Y., Shen, P., Mao, R., Yu, L., Zhao, M., & Li, Q. (2015). Gut Microbiota Community and Its Assembly Associated with Age and Diet in Chinese Centenarians. Journal of microbiology and biotechnology, 25(8), 1195–1204.
[3] Kong, F., Hua, Y., Zeng, B., Ning, R., Li, Y., & Zhao, J. (2016). Gut microbiota signatures of longevity. Current biology : CB, 26(18), R832–R833.
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[6] Zhao, Y., Li, C., Luan, Z., Chen, J., Wang, C., Jing, Y., Qi, S., Zhao, Z., Zhang, H., Wu, J., Chen, Y., Li, Z., Zhao, B., Wang, S., Yang, Y., & Sun, G. (2023). Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis. Scientific reports, 13(1), 12946.
[7] Yun, S., Park, H., Shin, Y., Ma, X., Han, M. J., & Kim, D. (2023). Lactobacillus gasseri NK109 and Its Supplement Alleviate Cognitive Impairment in Mice by Modulating NF-κB Activation, BDNF Expression, and Gut Microbiota Composition. Nutrients, 15(3), 790.
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[10] Martín, R., Rios-Covian, D., Huillet, E., Auger, S., Khazaal, S., Bermúdez-Humarán, L. G., Sokol, H., Chatel, J. M., & Langella, P. (2023). Faecalibacterium: a bacterial genus with promising human health applications. FEMS microbiology reviews, 47(4), fuad039.
[11] Collino, S., Montoliu, I., Martin, F. P., Scherer, M., Mari, D., Salvioli, S., Bucci, L., Ostan, R., Monti, D., Biagi, E., Brigidi, P., Franceschi, C., & Rezzi, S. (2013). Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PloS one, 8(3), e56564.
[12] Montoliu, I., Scherer, M., Beguelin, F., DaSilva, L., Mari, D., Salvioli, S., Martin, F. P., Capri, M., Bucci, L., Ostan, R., Garagnani, P., Monti, D., Biagi, E., Brigidi, P., Kussmann, M., Rezzi, S., Franceschi, C., & Collino, S. (2014). Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity. Aging, 6(1), 9–25.
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