Microbiome-Based Aging Clock: Toward the Prediction of the Biological Age?

Have you ever heard about “gut clock” as a byproduct of gut microbiota analysis? It looks like our inner microbes are not only the wardens of our health but also of our lifespan… Characterizing biological aging may help us to predict people’s susceptibility to diseases.  Let’s focus on 4 examples of microbiome-associated aging clocks:

1. Diversity clock: age-related decline in gut microbiome biodiversity can be used to determine biological age. Sala et al. [1] proposed a diversity-based model for estimating healthy aging, the ‘Hybrid Niche Nature Model’, focusing on rare and most abundant species compared to the traditional methods for richness and evenness. Based on the ELDERMET study (the most comprehensive study of microbiome data from older people), the model represented a better predictor of the health status in aged individuals than the commonly used diversity index (Shannon, etc..).

2. Taxonomic clock: the methanogenic archaea Methanobrevibacter smithii, a key player in energy harvest, shifts to a younger predicted age and increases significantly in centenarians. Interestingly, compared with younger individuals, centenarians show an increase also in Akkermansia muciniphila, while Campylobacter jejuni is a marker of higher biological age.

3. Functional clock: through a comprehensive multi-omic analysis, Gopu et al. [2] found that microbial expression patterns could predict biological age. By analyzing meta-transcriptomic profiles of approximately 90k individuals, with a wide range of age and lifestyle habits, a strong positive correlation was found between microbial methanogenesis pathways and aging. Negative correlations included SCFA production, vit B12 biosynthesis, and amino acid metabolism. The “metatranscriptomic clock” also suggested that vegetarian people look biologically younger than those on a paleo diet.

4. Metametabolomic clock: circulating metabolites of blood, urine, or stool can help establish an aging clock. For example, using plasma metabolomic profiles of individuals between 18 and 80 years old, Johnson et al. [3] identified 21 metabolites that are associated with biological age. Interestingly, these molecules were previously identified as microbe-associated metabolites, as putrescine and indole-3-acetate (lower biological age), and phaseolic acid (higher biological age).

By integrating insights from the host and microbiome’s clocks, biological aging can be predicted (or even reverted?) through corrective dietary and lifestyle intervention as part of the "intestinal rejuvenation’’ strategy. How far are we from that? 👨‍⚕️ 🚀 

Link to the paper: https://doi.org/10.3390/microorganisms10030668

References

[1] Sala, C., Giampieri, E., Vitali, S., Garagnani, P., Remondini, D., Bazzani, A., ... & Castellani, G. C. (2020). Gut microbiota ecology: Biodiversity estimated from hybrid neutral-niche model increases with health status and aging. Plos one, 15(10), e0237207. https://doi.org/10.1371/journal.pone.0237207

[2] Gopu, V., Cai, Y., Krishnan, S., Rajagopal, S., Camacho, F. R., Toma, R., ... & Tily, H. (2020). An accurate aging clock developed from the largest dataset of microbial and human gene expression reveals molecular mechanisms of aging. BioRxiv, 2020-09. https://doi.org/10.1101/2020.09.17.301887

[3] Johnson, L. C., Parker, K., Aguirre, B. F., Nemkov, T. G., D’Alessandro, A., Johnson, S. A., ... & Martens, C. R. (2019). The plasma metabolome as a predictor of biological aging in humans. Geroscience, 41, 895-906. https://doi.org/10.1007/s11357-019-00123-w

[4] Ratiner, K., Abdeen, S. K., Goldenberg, K., & Elinav, E. (2022). Utilization of host and microbiome features in determination of biological aging. Microorganisms, 10(3), 668. https://doi.org/10.3390/microorganisms10030668