Biology subjects

Rogina, B.

Publications and source records attributed to Rogina, B..

3 recordsLinked to original sources

bioRxiv2026

Microbiome contribution to Indy longevity in Drosophila

Reduction in the Indy (Im not dead yet) gene, a plasma membrane citrate transporter, in Drosophila and its homolog in worms extends lifespan by promoting metabolic homeostasis. Indy reduction delays the onset of aging-associated pathology in the fly midgut, including preservation of intestinal barrier integrity and intestinal stem cell homeostasis. Gut microbiota has broad impacts on host metabolism, health, and aging. Age-related dysbiosis impairs intestinal barrier function and drives mortality. However, the underlying mechanisms that link increased microbial load to frailty and negative effects on health remain mostly unclear. Here we show that Indy heterozygote flies have significantly lower bacterial load and increased diversity during aging compared to controls. However, the presence of the microbiome was not required for Indy lifespan extension, though removal of microbes did enhance the effects of Indy reduction on longevity, suggesting potential interactions between the microbiome and Indy. Indy down-regulation was linked to reduced expression of the JAK/STAT signaling ligands Upd3 and Upd2 in the midgut of young flies, which likely contributes to preserved intestinal stem cell homeostasis. Altogether, our results suggest that Indy reduction impacts microbiome load and composition, which preserves gut homeostasis and extends lifespan through impacts on JAK/STAT signaling pathway. Significance StatementIndy is a fly homologue of mammalian SLC13A5 (mSLC13A5) plasma membrane citrate transporter, a central metabolic regulator involved in health, longevity, and disease. Reduction of fly Indy gene activity preserves metabolic and intestinal stem cell homeostasis and extends longevity. Gut microbiota impacts host metabolism, health, and aging. Here we show that Indy reduction prevents age-associated increases in bacterial load and expression of the JAK/STAT signaling ligands Upd3, and Upd2, while maintaining microbiome diversity. These changes likely slow activation of epithelial cell turnover in the gut and contribute to downstream lifespan effects. As the role of INDY and microbiome are conserved across organisms, our study provides a framework to study underlying mechanisms of the effects of reduced Indy and the microbiome on health and longevity.

genetics↗

bioRxiv2023

Extended lifespan in female Drosophila melanogaster through late-life caloric restriction.

Calorie restriction has many beneficial effects on healthspan and lifespan in a variety of species. However, how late in life application of caloric restriction can extend fly life is not clear. Here we show that late-life calorie restriction increases lifespan in female Drosophila melanogaster aged on a high calorie diet. This shift results in rapid decrease in mortality rate and extends fly lifespan. In contrast, shifting female flies from a low to a high calorie diet leads to a rapid increase in mortality and shorter lifespan. These changes are mediated by immediate metabolic and physiological adaptations. One of such adaptation is rapid adjustment in egg production, with flies directing excess energy towards egg production when shifted to a high diet, or away from reproduction in females shifted to low caloric diet. However, lifelong female fecundity reveals no associated fitness cost due to CR when flies are shifted to a high calorie diet. In view of high conservation of the beneficial effects of CR on physiology and lifespan in a wide variety of organisms, including humans, our findings could provide valuable insight into CR applications that could provide health benefits later in life.

physiology↗

bioRxiv2023

Late- life shift in caloric intake affects fly longevity and metabolism

Caloric restriction (CR) delays the onset of age-related changes and extends lifespan in most species, but how late in life organisms benefit from switching to a low-calorie (L) diet is unexplored. We transferred wild type male flies from a high- (H) to a L-calorie diet (HL) or vice versa (LH) at different times. Late-life HL shift immediately and profoundly reduces fly mortality rate to briefly lower rate than in flies on a constant L diet, and increases lifespan. Conversely, a LH shift increases mortality and hazard rate, which is temporarily higher than in flies aged on a H diet, and leads to shorter lifespan. Transcriptomic changes within 48 hours following diet shift uncover physiological adaptations to available nutrients. Unexpectedly, more abundant transcriptomic changes accompanied LH shift, including ribosome biogenesis, and promotion of growth, which likely contributes to higher mortality rate. Considering that the beneficial effects of CR on physiology and lifespan are conserved across many organisms, our findings suggest that CR interventions in older humans may counteract the detrimental effects of H diets even when initiated later in life.

physiology↗