Title: Integrative systems analysis of healthspan modulation in Drosophila melanogaster through isocaloric macronutrient manipulation.

Abstract:

Aging is a progressive decline in physiological function that leads reduction in the organism’s resilience to stress. In present times, while we have different interventions aiming to extend lifespan, whether that translates to extended healthspan or better health in old age is a question of immense interest. Nutritional manipulation involving caloric restriction has been one of the successful interventions to extend the lifespan, however, the impact of macronutrient manipulation on lifespan and health status across age, while keeping the calorific value constant is largely overlooked. Furthermore, the effect of stage-specific nutrition, juvenile vs. adult, and their interaction on senescence has rarely been systematically investigated. Considering these nuances, we have designed a set of isocaloric nutrient regimes with different Protein and Carbohydrate ratios and dietary manipulation at two life stages of Drosophila melanogaster. Previous work from the lab suggests that low protein to carbohydrate (P: C) ratio diets reduce lifespan, while a high P: C diet shows no measurable effect compared to a control diet. Moving forward, we are now systematically characterizing the differential lifespan by measuring different hallmarks of aging across different levels of biological organization. Starting with Organismal stress response against abiotic stressors like starvation, desiccation, and heat, our preliminary data seem to suggest a stress-specific effect of different P: C ratio diets. We also found stark sexual dimorphism in starvation and desiccation resistance. Further, on the tissue level, we also explored energetic and neuromuscular health through mitochondrial DNA copy number estimation. Mitochondrial DNA copy number declined with age across treatments a characteristic of muscular senescence, but differed in number only at a young age indicating a stronger effect of age than diet. At the molecular level, to track transcript level changes we have proceeded with RNAseq analysis. Lastly, using experimental evolution lines, we also plan to understand the evolutionary implications of multigenerational dietary manipulation on healthspan and aging. Given the divergent effect of diet on different hallmarks of aging, taking a systemic approach to understand both plastic and evolved response will not only help us decouple lifespan and healthspan but also advance our understanding of dietary mismatches and associated diseases.

About the Speaker:
Devashish did his MSc in Life Sciences from Jawaharlal Nehru University, Delhi. His research interest lies in understanding how various environmental factors notably diet affect the aging in eukaryotic organisms. For his Ph.D. work, he is looking into both the single-generation and long-term evolutionary implications of diet on aging using Drosophila melanogaster as a model system. When not on the bench he likes to play Cricket, read non-fiction novels, and cook.