Increased Internal and External Bacterial Load during Drosophila Aging without Life-Span Trade-Off

Ren, Chunli; Webster, Paul; Finkel, Steven E.; Tower, John

doi:10.1016/j.cmet.2007.06.006

Cited by 323 publications

(379 citation statements)

References 51 publications

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“…S3D). These findings are consistent with a previous report of increased bacterial loads in aged flies (22) and indicate that loss of intestinal integrity in aged flies is associated with changes in the fly microbiome.…”

supporting

confidence: 93%

Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila

Rera¹,

Clark²,

Walker

2012

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

520

747

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Aging is characterized by a growing risk of disease and death, yet the underlying pathophysiology is poorly understood. Indeed, little is known about how the functional decline of individual organ systems relates to the integrative physiology of aging and probability of death of the organism. Here we show that intestinal barrier dysfunction is correlated with lifespan across a range of Drosophila genotypes and environmental conditions, including mitochondrial dysfunction and dietary restriction. Regardless of chronological age, intestinal barrier dysfunction predicts impending death in individual flies. Activation of inflammatory pathways has been linked to aging and age-related diseases in humans, and an age-related increase in immunity-related gene expression has been reported in Drosophila. We show that the age-related increase in expression of antimicrobial peptides is tightly linked to intestinal barrier dysfunction. Indeed, increased antimicrobial peptide expression during aging can be used to identify individual flies exhibiting intestinal barrier dysfunction. Similarly, intestinal barrier dysfunction is more accurate than chronological age in identifying individual flies with systemic metabolic defects previously linked to aging, including impaired insulin/insulin-like growth factor signaling, as evidenced by a reduction in Akt activation and upregulation of dFOXO target genes. Thus, the age-dependent loss of intestinal integrity is associated with altered metabolic and immune signaling and, critically, is a harbinger of death. Our findings suggest that intestinal barrier dysfunction may be an important factor in the pathophysiology of aging in other species as well, including humans.ging involves the accumulation of damage to molecules, cells, and tissues, resulting in a decline in physiological functions and ultimately leading to an increased probability of death (1). Considerable progress has been made toward identifying genetic and environmental factors that modulate aging and lifespan, mainly as a result of pioneering work in invertebrate models, such as the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster (2). Our understanding of the integrative pathophysiology of aging and age-onset mortality remains very limited, however (3). A number of markers of human aging and age-onset disease have been identified, including a chronic state of inflammation (4) and the development of insulin resistance (5). In a similar fashion, Drosophila aging is also associated with the increased expression of immunity-related genes (6, 7) and characteristics of insulin/insulin-like growth factor signaling (IIS) impedance (8). The relationships between these different metabolic and inflammatory markers of aging and how they relate to age-related pathological changes remain unexplored, however. Moreover, although Drosophila is an important model for studying the genetics of aging, the ability to predict the age at which a fly will die based on a decline in organ function has proven elusive.The inte...

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supporting

confidence: 93%

Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila

Rera¹,

Clark²,

Walker

2012

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

520

747

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“…Numerous studies have surveyed the gut microbes of Drosophila and identified bacterial communities far less complex than mammals (Corby-Harris et al 2007;Cox and Gilmore 2007;Ren et al 2007;Ryu et al 2008;Chandler et al 2011;Wong et al 2011). An analysis of both laboratory-raised and wild-caught flies found a maximum of 30 operational taxonomic units (OTUs), a proxy for species commonly employed in 16S rRNA gene sequencing analysis, associated with some wild Drosophila, and an average of 6.3 OTUs with laboratory-reared flies (Chandler et al 2011).…”

Section: Fruit Flymentioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.The distinctive body plans of animals offer many niches for members of the archaeal and bacterial kingdoms. While the lumen of the human distal gut is one of the most densely populated ecosystems on our planet, humans and other animals harbor several microbiomes on and within their body surfaces such as the respiratory and urogenital tracts and the skin. As the gut has evolved from the relatively simple tube of the ancient cyclostomatida to the more highly compartmentalized gastrointestinal tracts of mammalian species, the diversity and complexity of the microbial inhabitants of those spaces has increased as well (Fig.

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“…Gut microbes also play a role in invertebrate biology (Dillon and Dillon, 2003) and digestive process [Brune, 2011 [Lundgren, 2010, and recently the composition of microbe gut populations has been described in a variety of insect species, including bees (Jeyaprakash et al, 2003;Mohr and Tebbe, 2006), beetles (Egert et al, 2005;Lehman et al, 2009;Nardi et al, 2006;Zhang and Jackson, 2008), flies (Cox and Gilmore, 2007;Ren et al, 2007;Ryu et al, 2008;Shin et al, 2011;Wong et al, 2011), lepidopterans (Pauchet et al, 2010;Xiang et al, 2006) and termites (Hongoh et al, 2003). In Drosophila, the microbiome regulates host metabolic homeostatic and developmental programs by modulating the insulin/insulin-like growth factor (Shin et al, 2011).…”

Section: Microbiota: a Key Component Of Nutritional Immunologymentioning

confidence: 99%