You Are What You Host: Microbiome Modulation of the Aging Process

“Transplanting microbiota from genetically obese ob/ob mice into germ-free lean C57BL/6J mice induces obesity in the recipients compared to controls despite similar caloric intake (Turnbaugh et al., 2006), suggesting that their ability to glean nutrients is affected by themicrobes.”

“As humans age, the composition of our microbiome changes (Yatsunenko et al., 2012).”

“Commensal bacteria can affect the nutrient landscape of the host—the majority of metabolites in human plasma are microbe-derived (Nicholson et al., 2012)—but recent work suggests that bacterial-derived metabolites can affect host longevity.”

“Despite coevolving in the presence of this ‘‘microbiome’’ for 500million years (Cho and Blaser, 2012), only recently have advances in sequencing technology allowed us to appreciate the complexities of this relationship and the manner by which genomes within metaorganisms interact and affect one…”

“Unlike worms, the effect of associated bacteria on Drosophila lifespan is less clear and may depend upon the precise composition of the microbiota population.”

“However, microRNAs derived from plants are present in human and rodent serum and tissues (Zhang et al., 2012), suggesting such interspecies communication is feasible.”

“Metformin increases lifespan in rodents (Martin-Montalvo et al., , January 30, 2014 ª2014 Elsevier Inc. 409 2013), and a side effect of metformin treatment in humans is reduced folate levels (Cabreiro et al., 2013).”

“Flies overexpressing the inhibitor of TOR complex 1 are resistant to the effects of L. plantarum on growth (Storelli et al., 2011).”

“Rictor mutants are short lived when cultured on standard B-derived OP50 bacteria, yet when grown on the K12derived E. coli HT115, they are long lived by 76% (Soukas et al., 2009).”

“Invertebrate model systems such as the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans (C. elegans) also live in the presence of microbiota both in nature and in the laboratory (Ren et al., 2007; Zhang and Hou, 2013).”

“Early reports suggested that culturing Drosophila axenically shortened lifespan, with the presence of bacteria within the first week of adult life slowing aging (Brummel et al., 2004).”

“Interestingly, worms are acutely sensitive to signals emanating from DA1877; diluting OP50 with only 0.1% DA1877 still suppressed the reporter and induced similar transcriptional responses to DA1877 alone (MacNeil et al., 2013).”

“Direct Interspecies Signaling and Aging Given the proximity of microbes and host within the metaorganism, diffusible molecules originating in bacteria can directly affect cells in the host (Ryan and Dow, 2008).”

“This effect on worm lipid composition is abolished in animals lacking the peptide transporter PEPT-1 (Brooks et al., 2009).”

“Snell dwarfmice, deficient in thyroid hormone, are long lived by up to 50%, yet decades earlier, thesemice were touted as a model of rapid aging and progeria (Flurkey et al., 2002).”

“Culturing worms axenically robustly increases their lifespan (Houthoofd et al., 2002).”

“As a critical signaling molecule, NO has been implicated in multiple functions, including neurotransmission, immunity, and cardiovascular function (Gusarov et al., 2013).”

“Feeding E. coli expressing a double-stranded C. elegans RNA sequence efficiently suppresses the worm gene (Liu et al., 2012).”

“Hence, DA1877 can induce whole-scale metabolic responses in the worm to modulate development and aging (Watson et al., 2013) (Figure 1D).”

“Metformin suppresses folate metabolism specifically in E. coli, and feeding worms either the antibiotic trimethoprim, which inhibits dihydrofolate reductase in bacteria, or E. coli mutants with suppressed folate metabolism (Virk et al., 2012) also increases lifespan.”

“Tipping the balance toward quiescence limits intestinal rejuvenation, whereas ISC overproliferation causes epithelial dysplasia (Jasper and Jones, 2010).”

“Invertebrate model systems such as the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans (C. elegans) also live in the presence of microbiota both in nature and in the laboratory (Ren et al., 2007; Zhang and Hou, 2013).”

“The potential impact of concurrent low-grade infections, or even of microbiome (Heintz and Mair 2014), on astrogliosis and responses to CNS insults is likely to be an interesting area of future research.”