Exploring the relationship between epigenetic aging and gut microbiome composition in physically fit men and women

In a recent study posted to the medRxiv* preprint server, researchers investigate the relationship between the gut microbiome, physical fitness, and epigenetic aging in physically fit individuals.

Study: Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness. Image Credit: wavebreakmedia / Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background 

Numerous studies have reported that a healthy lifestyle can enhance an individual’s lifespan and reduce lifestyle-related diseases. Epigenetic clocks, which measure biological age and are influenced by lifestyle and genes, accurately predict age and have been associated with biomarkers and mortality risk.

Recently, researchers have developed DNAmFitAge based on genes related to physical fitness, in which physically fit individuals appear to have a younger biological age and better age-related outcomes. The microbiome, which is a highly adaptable system, changes with age, thereby impacting immunity, inflammation, and longevity.

Exploring the connection between the microbiome, epigenetic aging, and fitness levels can significantly improve the current understanding of human health, diseases, and aging. 

About the study

In the present study, researchers investigate the gut microbiome of 80 physically fit individuals between 38 to 84 years of age. This data was analyzed to determine the relationship between the microbiome, physical fitness, and epigenetic age acceleration. 

Maximal oxygen uptake was measured to assess cardiovascular fitness, whereas maximum handgrip force and vertical jump were used to evaluate overall muscle and leg strength, respectively. Body mass index (BMI) values were determined using a body composition monitor.

Plasma irisin levels were quantified using enzyme-linked immunosorbent assay (ELISA), whereas redox balance was calculated based on antioxidant power and reactive oxygen metabolites. Stool samples were also collected for microbiome analysis and DNA extraction. 

Illumina sequencing was used to analyze microbial DNA, whereas bioinformatics analysis assessed the quality of the reads and taxonomic characterization. Epigenome-wide DNA methylation was measured using the Infinium MethylationEPIC BeadChip.

DNA methylation aging clocks were applied using Horvath’s online age calculator and the DunedinPACE package. Statistical analysis was performed using Python packages, including t-tests and Pearson correlation coefficients, for comparisons and correlations, respectively. 

Study results

Gender differences were observed in the gut microbiome composition, with Firmicutes and Proteobacteria more abundant in males and females, respectively. Associations were also observed between epigenetic aging and microbiome diversity, thus suggesting that increased microbial entropy may be linked to accelerated epigenetic aging.

At the species level, certain bacteria were positively or negatively associated with epigenetic aging, such as Bifidobacterium adolescentis and Escherichia coli in males, and Bacteroides uniformis and Bacteroides vulgatus in females. 

Collinsella aerofaciens, which is associated with mental disorders and inflammation, also showed a positive correlation with age acceleration in males. Conversely, anti-inflammatory Anaerostipes hardus exhibits a negative correlation.

Bacterial abundances related to epigenetic aging do not align with chronological age. This indicates a potential causative relationship between proinflammatory bacteria and age acceleration.

Examination of bacterial pathways indicated an association between age acceleration and fitness-related parameters. For example, cytidine diphosphate (CDP)-diacylglycerol and flavin biosynthesis pathways revealed negative correlations with age acceleration in males but positive correlations in females. 

The researchers further explored the relationship between the microbiome and exercise-related measurements. In males, microbial diversity correlated negatively with JumpMax, VO2max, and Redox Balance, and positively with triglyceride levels. In females, microbial diversity correlated negatively with BMI and cognitive test performance.

Specific bacterial species were associated with exercise-related parameters. In females, age acceleration was linked to Dorea longicatena, which is associated with metabolic risks in obesity, and Bacteroidetes, specifically Bacteroides uniformis and Bacteroides vulgatus, which are linked to ulcerative colitis severity.

Fusicatenibacter saccharivorans showed a strong positive correlation with VO2max in males, possibly due to its anti-inflammatory properties and production of short-chain fatty acids. Eubacterium Sp. CAG 180 negatively correlated with grip strength and jump height.

Redox balance was positively associated with specific molecular pathways, whereas irisin levels negatively correlated with the cap-diacylglycerol pathway in females. These observations suggest potential connections between cognitive performance, hormone levels, and metabolic pathways.

Conclusions

The microbiome is dynamic and responsive to factors like nutrition, exercise, and health while also exhibiting stability over time. Gender differences in lifespan, hormones, and fitness levels contribute to variations in the microbiome.

Firmicutes and Bacteroidetes are the dominant phyla in the gut microbiome of healthy individuals; however, their proportions differ in highly fit athletes. An increased presence of Proteobacteria correlates positively with age acceleration in males, which may influence epigenetic aging, whereas anti-inflammatory Anaerostipes hardus shows a negative correlation.

In females, age acceleration is linked to Dorea longicatena, Bacteroides uniformis, and Bacteroides vulgatus, which are associated with metabolic risks and ulcerative colitis severity. Fusicatenibacter saccharivorans correlates positively with VO2max in males, while Eubacterium Sp. CAG 180 negatively impacts physical performance.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Vijay Kumar Malesu

Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.    

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