Impact of Age, Sex and Mitochondrial DNA on Gut Microbiome

A new research paper was published in Aging (Aging-US) on February 27, 2025, in Volume 17, Issue 2, titled “Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model.”

The research team, led by first author Hoang Van M. Nguyen and corresponding author Archana Unnikrishnan from the University of Oklahoma Health Sciences, studied how aging affects gut bacteria in a special group of rats generated to have genetic diversity similar to humans. Their research found that both biological sex and mitochondrial DNA – the small set of genes inherited only from mothers – play a key role in how gut bacteria change over time.

The gut microbiome, a collection of bacteria in the intestines, affects digestion, metabolism, and even brain function. As people age, these bacteria shift, and some of these changes are linked to diseases like Alzheimer’s, Parkinson’s, and metabolic disorders. However, most studies have looked at either men or women without comparing differences between sexes, and few have explored how mitochondrial DNA might influence these changes.

To better understand these factors, researchers analyzed fecal samples from the genetically diverse rats to assess gut bacteria composition and metabolic byproducts. The results showed that aging affects gut bacteria differently in males and females. More bacterial species changed with age in female rats than in males, and only a few changes were consistent across both sexes. These findings suggest that men and women may experience aging differently at the microbial level, which could impact nutrition and disease risk.

Another key discovery was that mitochondrial DNA influences how gut bacteria evolve with age. These effects were different in males and females, suggesting a deeper connection between mitochondrial function and gut health, with potential implications for personalized medicine and aging research.

In addition to studying bacteria, the researchers analyzed metabolic compounds such as short-chain fatty acids and bile acids, which help with digestion. They found that aging altered these compounds based on both sex and mitochondrial DNA. For example, older female rats had higher levels of short-chain fatty acids in their feces, possibly due to differences in nutrient absorption.

This study highlights new factors that shape the gut microbiome in aging populations. Understanding how biological sex and mitochondrial DNA influence these changes could lead to targeted approaches for maintaining gut health and preventing age-related diseases. These findings reinforce the importance of personalized health strategies that consider both genetic and biological differences.

Reference: Nguyen HVM, Cabello E, Dyer D, et al. Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model. Aging. 2025;17(2):524-549. doi: 10.18632/aging.206211

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