As life expectancy rises across Asia, a key question remains: will people age in good health? With over a third of the region’s population projected to be 60 years or older by 2050, understanding the factors that shape healthy ageing is increasingly urgent.
A key player might be our gut microbiomes. As we age, these microbial communities shift in ways linked to frailty and disease. Yet most studies so far offer only a low-resolution view of these connections, noted Aarthi Ravikrishnan, a Senior Scientist at the A*STAR Genome Institute of Singapore (A*STAR GIS).
“Older genomic methods, such as 1Gs rRNA sequencing, only detect microbes that match specific genes,” Ravikrishnan said. “It’s like assessing the variety of mixed Lego bricks by focusing on the most common colours.”
To dive deeper, recent studies have turned to shotgun metagenomics, a next- generation DNA sequencing technique that breaks up all the genetic material present in a sample, then randomly sequences them, increasing the odds of catching rare species.
“Shotgun metagenomics is a powerful tool for studying the full diversity of complex microbial communities in detail,” added Indrik Wijaya, a former A*STAR GIS Bioinformatics Specialist.
Still, many studies remain constrained by small cohort sizes, making it difficult to account for confounding factors such as diet, medication and lifestyle. To get a clearer view, Ravikrishnan and Wijaya worked with colleagues at A*STAR GIS including Niranjan Nagarajan, Associate Director and Senior Group Leader; the A*STAR Singapore Immunology Network (A*STAR SIgN); A*STAR Institute for Human Development and Potential (A*STAR IHDP); and Yong Loo Lin School of Medicine, National University of Singapore. They applied shotgun metagenomics on a large cohort from SG50: a decades-long population study of community-dwelling elderly persons in Singapore.
“[SG50] provided a rich health dataset which helped us effectively control for those confounding factors in our models,” said Ravikrishnan.
With metagenomic profiles from over 200 SG50 participants, the team integrated data from younger Singaporean and Asian cohorts into statistical models, looking for age-related patterns.
“One thing that stood out was the age-related decline of Faecalibacterium prausnitzii, a key butyrate-producing bacterium. Butyrate maintains gut health by reducing inflammation, supporting gut barrier integrity and facilitating gut-brain communication,” said the researchers.
They added, “Intriguingly, F. prausnitzii’s decline came with the rise of Alistipes and Bacteroides species that teamed up to become major butyrate producers, potentially taking over F. prausnitzii’s role in gut health. We saw these functional enrichments repeated in mouse models of healthy ageing, suggesting they may play similar roles in promoting that state.”
Moving forward, the team plans to isolate and characterise key microbial strains linked with healthy ageing, and assess their effectiveness as supplements to reduce frailty. “We believe these experiments will provide critical insights and facilitate the translation of our findings into practical applications for improving healthy ageing,” they concluded.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Genome Institute of Singapore (A*STAR GIS), A*STAR Singapore Immunology Network (A*STAR SIgN) and A*STAR Institute for Human Development and Potential (A*STAR IHDP).
