New Research Suggests Ageing and Reflux Are Genetically Linked?

As we age, it’s not unusual to experience new or worsening digestive symptoms, including heartburn, regurgitation or chest discomfort associated with gastro-oesophageal reflux disease (GORD/GERD).

But while lifestyle changes and age-related physical changes are often blamed, new genetic research suggests that ageing and reflux may actually share a deeper biological connection.

A 2025 study published in Scientific Reports has examined the genetic overlap between GORD and age-related traits using advanced genome-wide analysis. The research identified several genetic variants and biological pathways that may influence both conditions, offering a fresh perspective on why reflux becomes more common and more persistent in older adults.

Understanding GORD and ageing

GORD is a chronic condition where acid or other stomach contents flow back into the oesophagus, causing irritation and uncomfortable symptoms. Studies already show that the condition becomes more common with age, likely because muscles weaken, digestion changes, or certain medications have cumulative effects.

However, this new study took a different approach. Instead of focusing on the physical effects of ageing, the researchers explored whether GORD and key signs of biological ageing share genetic characteristics.

In other words, whether people who are genetically predisposed to certain ageing traits might also be more likely to develop reflux.

To do this, the team used data from genome-wide association studies (GWAS) involving individuals of European ancestry. They examined five ageing-related traits:

• Frailty Index (FI) – a measure of physical vulnerability
• Telomere Length (TL) – a well-known marker of biological ageing
• Longevity
• Parental lifespan (PL)
• Facial ageing (FA)

The researchers then compared these traits with GWAS data on GORD to look for shared genetic markers, using several advanced statistical methods including LDSC, HDL, PLACO, FUMA and MAGMA.

Key findings

Two traits in particular – frailty and telomere length – showed the strongest genetic connection to GORD.

Frailty Index (FI) was found to be positively correlated with GORD at the genetic level. This supports previous clinical findings that older adults with frailty are more likely to experience reflux symptoms. The researchers identified 73 genetic variants (SNPs) that may influence both frailty and GORD, suggesting a common biological vulnerability.

Some of these genes, including SCAI and OLFM4, are also linked to brain health and conditions such as depression and sleep disorders. This raises interesting questions about the brain-gut axis; the connection between the digestive system and the central nervous system; and how it might influence both ageing and reflux.

Telomere Length (TL), which shortens as we age, was also genetically associated with a higher risk of GORD. The study identified 148 shared genetic markers between TL and GORD. One of these, near the gene FAM49A, may play a role in both cellular ageing and digestive function, although further research is needed to clarify its role.

The researchers did not find strong genetic links between GORD and facial ageing, and only minimal links with longevity and parental lifespan. This suggests that biological markers of ageing (like frailty and telomere length) may be more relevant to reflux than appearance-based or lifespan traits.

How were these results found?

To ensure the reliability of their results, the research team applied multiple cross-checking methods, including:

• PLACO helped identify genetic variants that influence both traits (pleiotropy)
• FUMA was used to map and annotate these variants to specific genes
• Bayesian colocalisation confirmed whether GORD and ageing traits shared the same causal genetic regions
• MAGMA provided gene and tissue-specific analysis, revealing that some of the shared genes were most active in areas of the brain, including the cortex and frontal cortex

This layered approach helped ensure that the findings were not just statistically significant but also biologically meaningful.

What does this mean for people with GORD?

The research does not suggest that ageing causes reflux, or that reflux is inevitable with age. Instead, it highlights that some individuals may be genetically predisposed to both biological ageing and reflux symptoms, potentially making them more susceptible as they grow older.

For people who experience GORD later in life, especially when symptoms are persistent or don’t fully respond to treatment, this research may help explain why. It also reinforces the importance of individualised diagnosis and management, particularly as we learn more about how genetic and biological factors shape our digestive health.

Future studies may expand on this work by including more diverse populations and exploring the functional role of specific genes.

Why testing matters

Understanding whether your symptoms are truly caused by reflux is an important first step. At Peptest, we offer a non-invasive diagnostic test that detects pepsin: a stomach enzyme not normally found outside the digestive tract. If pepsin is found in saliva, it suggests that reflux is occurring.

For older adults experiencing persistent symptoms, or for anyone considering long-term medication, accurate testing like Peptest can help guide conversations with healthcare professionals and support more targeted treatment decisions.