Abstract
Gut bacteria occupy the interface between the organism and the external environment, contributing to homeostasis and disease. Yet, the causal role of the gut microbiota during host aging is largely unexplored. Here, using the African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, we show that the gut microbiota plays a key role in modulating vertebrate life span. Recolonizing the gut of middle-age individuals with bacteria from young donors resulted in life span extension and delayed behavioral decline. This intervention prevented the decrease in microbial diversity associated with host aging and maintained a young-like gut bacterial community, characterized by overrepresentation of the key genera Exiguobacterium, Planococcus, Propionigenium and Psychrobacter. Our findings demonstrate that the natural microbial gut community of young individuals can causally induce long-lasting beneficial systemic effects that lead to life span extension in a vertebrate model.
Highlights
Life expectancy of different species in nature is regulated by a complex combination of genetic and non-genetic factors
The unique combination of a complex gut microbial composition, similar to that of other vertebrate aging model organisms, and its naturally short life span, combined with a wide spectrum of aging phenotypes, makes the turquoise killifish an ideal system to study the role of the gut microbiota during vertebrate aging
Using the turquoise killifish (TK) as a naturally short-lived vertebrate model system, we report the characterization of the changes in gut microbiota (GM) composition occurring during aging and the discovery of a novel life span enhancing intervention achieved by acutely transferring young GM to middle-age individuals after antibiotic treatment
Summary
Life expectancy of different species in nature is regulated by a complex combination of genetic and non-genetic factors. Genetic manipulations in model organisms have revealed key conserved molecular pathways, including the insulin-IGF1 and the mTOR pathways, which regulate aging and life span across several species, spanning from yeast to mammals (Kapahi et al, 2010; Kenyon et al, 1993; Lapierre and Hansen, 2012). Environmental interventions such as temperature and dietary manipulations have been importantly associated with life span modulation in several species. These microbial communities participate in a wide range of key biological processes, including nutrient absorption (Semova et al, 2012), development (Sommer and Backhed, 2013), metabolism (Nicholson et al, 2012), immune modulation (Geva-Zatorsky et al, 2017), defense against pathogens (Kamada et al, 2013; Schuijt et al, 2016) and disease (Sampson et al, 2016)
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