How animals achieve their specific body size is a fundamental, but still largely unresolved, biological question. Over the past decades, studies on the insect model system have provided some ...important insights into the process of body size determination and highlighted the importance of insulin/insulin-like growth factor signaling. Fat body, the Drosophila counterpart of liver and adipose tissue, senses nutrient availability and controls larval growth rate by modulating peripheral insulin signaling. Similarly, insulin-like growth factor I produced from liver and muscle promotes postnatal body growth in mammals. Organismal growth is tightly coupled with the process of sexual maturation wherein the sex steroid hormone attenuates body growth. This review summarizes some important findings from Drosophila and mammalian studies that shed light on the general mechanism of animal size determination.
The mechanism that determines the specific body size of an animal is a fundamental biological question that remains largely unanswered. This aspect is now beginning to be understood in insect models, ...particularly in
, with studies highlighting the importance of nutrient-responsive growth signaling pathways involving insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) (IIS/TOR). These pathways operate in animals, from insects to mammals, adjusting the growth rate in response to the nutritional condition of the organism. Organismal growth is closely coupled with the process of developmental maturation mediated by maturation steroid hormones, which is influenced greatly by environmental and nutritional conditions. Recent
studies have been revealing the mechanisms responsible for this phenomenon. In this review, I summarize some important findings about the steroid hormone regulation of
body growth, calling attention to the influence of developmental nutritional conditions on animal size determination.
Transposable elements (TEs) are DNA elements that can change their position within the genome, with the potential to create mutations and destabilize the genome. As such, special molecular systems ...have been adopted in animals to control TE activity in order to protect the genome. PIWI proteins, in collaboration with PIWI-interacting RNAs (piRNAs), are well known to play a critical role in silencing germline TEs. Although initially thought to be germline-specific, the role of PIWI-piRNA pathways in controlling TEs in somatic cells has recently begun to be explored in various organisms, together with the role of endogenous small interfering RNAs (endo-siRNAs). This review summarizes recent results suggesting that these small RNA pathways have been critically implicated in the silencing of somatic TEs underlying various physiological traits, with a special focus on the
model organism.
Minocycline is a semi-synthetic tetracycline derivative antibiotic that has been examined for its non-antibiotic properties, such as anti-inflammatory, tumor-suppressive, and neuroprotective effects. ...In this study, we found that feeding minocycline to Drosophila improves proteostasis during organismal aging. Poly-ubiquitinated protein aggregates increase in the flight muscles as flies age, which are reduced in response to minocycline feeding. Minocycline feeding increases the expression of several autophagy genes and the activity of the autophagy/lysosomal pathway in Drosophila muscles. Interestingly, mutant flies lacking either FOXO or Hsp70 showed increased levels of poly-ubiquitinated protein aggregates with reduced autophagy/lysosomal activity, which was not reversed by minocycline feeding. Our findings suggest that minocycline may improve proteostasis in aging tissues via FOXO-Hsp70 axis, which highlights the multifaceted effects of minocycline as a therapeutic agent in age-associated features.
As cells age, they lose their ability to properly fold proteins, maintain protein folding, and eliminate misfolded proteins, which leads to the accumulation of abnormal protein aggregates and loss of ...protein homeostasis (proteostasis). Loss of proteostasis can accelerate aging and the onset of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Mechanisms exist to prevent the detrimental effects of abnormal proteins that incorporate chaperones, autophagy, and the ubiquitin-proteasome system. These mechanisms are evolutionarily conserved across various species. Therefore, the effect of impaired proteostasis on aging has been studied using model organisms that are appropriate for aging studies. In this review, we focus on the relationship between proteostasis and aging, and factors that affect proteostasis in
Drosophila.
The manipulation of proteostasis can alter lifespan, modulate neurotoxicity, and delay the onset of neurodegeneration, indicating that proteostasis may be a novel pharmacological target for the development of treatments for various age-associated diseases.
Commensal microbiota heavily influence metazoan host physiology. Drosophila melanogaster has been proven a valuable animal model for studying many aspects of host-microbiota interaction. ...Lactobacillus are the most common human probiotics and are also one of the major symbiotic bacteria in Drosophila. Although the beneficial effects of Lactobacillus on fly development and physiology have been recognized, how broadly these effects are observed across the Lactobacillus taxa remains largely unknown. In this study, four Lactobacillus species including five strains of L. plantarum were examined for their effects on fly larval development. Monoassociation of germ-free flies with L. rhamnosus (GG) most strongly accelerated fly larval development. Monoassociation with L. plantarum moderately accelerated fly development, but monoassociation with L. reuteri or L. sakei had marginal effects, despite similar bacterial loads in the host gut. An L. plantarum strain previously isolated from our lab rarely enhanced larval development, confirming the strain-specific effects of L. plantarum. The correlation between development-promoting effects and protein digestion activity in the host gut was found only among the members of L. plantarum species. Moreover, the cytoprotective response in the host gut known to be induced by L. plantarum was not correlated with development-promoting effects among any of the bacteria tested. Our results suggest that a broad range of Lactobacillus taxa are able to reside in the fly gut, but their ability to enhance host larval development is highly varied. This study may aid our understanding of the basic principles underlying the beneficial effects of probiotic commensal bacteria on metazoan development.
How body size is determined is a long-standing question in biology, yet its regulatory mechanisms remain largely unknown. Here, we find that a conserved microRNA miR-8 and its target, USH, regulate ...body size in Drosophila. miR-8 null flies are smaller in size and defective in insulin signaling in fat body that is the fly counterpart of liver and adipose tissue. Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously. Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively. USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. FOG2 directly binds to p85α, the regulatory subunit of PI3K, and interferes with the formation of a PI3K complex. Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer.
The gut microbiome plays a crucial role in maintaining health in a variety of organisms, from insects to humans. Further, beneficial symbiotic microbes are believed to contribute to improving the ...quality of life of the host. Drosophila is an optimal model for studying host-commensal microbe interactions because it allows for convenient manipulation of intestinal microbial composition. Fly microbiota has a simple taxonomic composition and can be cultivated and genetically tracked. This permits functional studies and analyses of the molecular mechanisms underlying their effects on host physiological processes. In this context, we briefly introduce the principle of juvenile developmental growth in Drosophila. Then, we discuss the current understanding of the molecular mechanisms underlying the effects of gut commensal bacteria, such as Lactiplantibacillus plantarum and Acetobacter pomorum, in the fly gut microbiome on Drosophila juvenile growth, including specific actions of gut hormones and metabolites in conserved cellular signaling systems, such as the insulin/insulin-like (IIS) and the target of rapamycin (TOR) pathways. Given the similarities in tissue function/structure, as well as the high conservation of physiological systems between Drosophila and mammals, findings from the Drosophila model system will have significant implications for understanding the mechanisms underlying the interaction between the host and the gut microbiome in metazoans.
Minocycline is a semi-synthetic tetracycline derivative antibiotic that has received increasing attention for its non-antibiotic properties, mainly anti-inflammatory, tumor-suppressive, and ...neuroprotective effects.
is a widely used genetically tractable model organism for studying organismal aging by virtue of its short lifespan and ease of cultivation. In this study, we examined the effects of minocycline on
lifespan and its associated traits. Minocycline-supplemented food significantly extended lifespan in both
and
strains. The drug-induced lifespan extension was not associated with reduced dietary intake or reduced female fecundity, but rather with increased resistance to an oxidative stressor (hydrogen peroxide). Notably, minocycline's effects on lifespan and resistance to oxidative stress were largely abrogated in
(
) null mutant, and the drug treatment increased the activity of FOXO. These results may further our understanding of minocycline's beneficial effects against several age-associated deteriorations observed in animal models.
Commensal microorganisms have a significant impact on the physiology of host animals, including Drosophila. Lactobacillus and Acetobacter, the two most common commensal bacteria in Drosophila, ...stimulate fly development and growth, but the mechanisms underlying their functional interactions remain elusive.
We found that imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor binding protein 7, is expressed in gut enterocytes in a bacteria-dependent manner, determining host dependence on specific bacteria for host development. Imp-L2 mutation abolished the stimulatory effects of Lactobacillus, but not of Acetobacter, on fly larval development. The lethality of the Imp-L2 mutant markedly increased under axenic conditions, which was reversed by Acetobacter, but not Lactobacillus, re-association. The host dependence on specific bacteria was determined by Imp-L2 expressed in enterocytes, which was repressed by Acetobacter, but not Lactobacillus. Mechanistically, Lactobacillus and Acetobacter differentially affected steroid hormone-mediated Imp-L2 expression and Imp-L2-specific FOXO regulation.
Our finding may provide a way how host switches dependence between different bacterial species when benefiting from varying microbiota.
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