Indoles Derived from Commensal Gut Bacteria Regulate Host Somatic and Reproductive Aging via the Interferon Pathway Público
Bhingarde, Jui (Spring 2018)
Abstract
Background:
At the cusp of the 20th century, public health advances have contributed a rapid increase in life expectancy to global populations by almost 30 years (Christensen et al. 2009). An increase in lifespan does not imply better health and decrease in healthcare cost, but increased longevity without health span improvement can lead to higher expenditures (Wouterse et al. 2015). Healthspan is broadly defined as the length of time that an individual remains healthy and free of age-related infirmities (Tissenbaum et al. 2012, Tatar et al. 2009). Gradual exposure to environmental stressors and lifestyle factors lead to deterioration of the body (Figure S1). Although there have been several studies identifying lifespan mechanisms, health span has received much less attention. Healthspan has often been convolved with lifespan, and extended health span has been associated with the slowed onset of normal age-related changes (e.g. sarcopenia). Here the research objective is to further evaluate evolutionarily conserved pathways that may be involved in extending health span.
Methods:
The study was conducted using lifespan experiments on a well-studied
Caenorhabditis elegans animal model, while statistical analysis was performed using PRISM to give survival analysis curves. Genetic mutants were exposed to indoles from E. coli bacterial strains and were tested against controls to see whether they exhibit different phenotypes.
Results:
The results showed a series of type I interferon pathway genes with elevated
exposure when C. elegans worms lacking certain genes exposed to indoles showed the similar response to worms not exposed to indoles. These genes are crucial in type I interferon pathway and provided further evidence to study the pathway and how indoles interacts with the genes.
Conclusions:
In conclusion, the study reported genes in the Type 1 interferon pathway that were upregulated by indole through a currently unknown mechanism. These results not only indicate the likelihood that the aging mechanism is modulated by the immune system but aging itself is a very complex phenomenon. These implications for the public health studies show that more information can be gathered through population genomic studies for understanding how they age.
Table of Contents
Chapter I
Introduction……………………....…………………………………………………..1
Materials and Methods……………………………………………….……...……..4
Results ………………………………………………………………..……………..6
Figures………………………………………………………………………...……..8
Chapter II
Introduction………………………………………………………………...……....10
Statistical Analysis…………………………………………………………..…….12
Results ………………………………………………………………………….....12
Discussion……………………………………………………………………..…..18
Supplementary Information……………………..………………………............21
References………………………………………………………………………..26
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