The process of ageing makes death increasingly likely, but involves a random aspect that produces a wide distribution of lifespan even in homogeneous populations1,2. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating how and how much specific molecular processes contribute to the aspect of ageing that determines lifespan.
This review will discuss the gut as a reservoir for antimicrobial resistance, colonization resistance, and how disruption of the microbiome can lead to colonization by pathogenic organisms. There is a focus on the gut as a reservoir for β-lactam and plasmid mediated quinolone resistance. Finally, the role of functional metagenomics and long read sequencing technologies to detect and understand antimicrobial resistance genes within the gut microbiome, and the potential for future microbiome-directed methods to detect and prevent infection is discussed.
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