Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Tazume, Seiki; Umehara, Keiko; Matsuzawa, Hideyuki; Aikawa, Hiroyuki; Hashimoto, Kazuo; Sasaki, Satoshi

doi:10.1538/expanim1978.40.4_517

Cited by 26 publications

(20 citation statements)

References 21 publications

(29 reference statements)

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“…In the Little mouse, CAR and PXR are not involved in the upregulation of xenobiotic metabolism (except for Cyp2b10 and Cyp2C38), but the effect was attributed to increased levels of bile acids and signaling through FXR. GF mice have a longer lifespan than SPF, but the effects of calorie restriction were similar on GF and SPF mice [38] and rats [36], [37]. The general theory is that the accumulation of toxic metabolic by-products is a major contributor to ageing [36].…”

Section: Discussionmentioning

confidence: 99%

Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

et al. 2009

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BackgroundThe liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates.Principal findingsBy comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia) when compared to the SPF group.ConclusionOur data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver.

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Section: Discussionmentioning

confidence: 99%

Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

et al. 2009

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“…We also set out to determine whether this lack of protection by CR was also observed when using longevity as the endpoint. For this study, we did not assess the effects of CR on WT mice, because it would be fully expected that CR would increase lifespan under these conditions as shown by others (41). Rather, we focused on the important question of whether the absence of Nrf2 would mitigate the effects of CR.…”

Section: Cr Does Not Require Nrf2 For Insulin Sensitivity or Increasementioning

confidence: 99%

Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

Pearson

Lewis

Price

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

212

156

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Caloric restriction (CR) is the most potent intervention known to both protect against carcinogenesis and extend lifespan in laboratory animals. A variety of anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and carcinogendetoxifying enzymes. Thus, Nrf2 offers a promising target for anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice to examine its role on the biological effects of CR. Here, we show that Nrf2 is responsible for most of the anticarcinogenic effects of CR, but is dispensable for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice developed tumors more readily in response to carcinogen exposure than did WT mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR extended lifespan and increased insulin sensitivity similarly in KO and WT mice. These findings identify a molecular pathway that dissociates the prolongevity and anticarcinogenic effects of CR.aging ͉ carcinogenesis ͉ oxidative stress

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“…Indeed, GF mice live longer than conventionally colonized control animals (Reyniers and Sacksteder, 1958; Gordon et al, 1966; Tazume et al, 1991). As GF mice are raised in sterile conditions, their longer life span is likely due to the absence of pathological infections.…”

Section: Introductionmentioning

confidence: 99%

Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior

Luczynski

Neufeld

Oriach

et al. 2016

IJNPPY

470

321

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There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.

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Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Cited by 26 publications

References 21 publications

Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior

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