Exploring Physiological Outcomes of a Dramatic Lifespan Extension due to a Double Mutation in C. elegans

Authors:

Zoe Nathwani, Nicole Stuhr, Sinclair Emans, Alex Soukas

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

Synergistic insulin signalling and mitochondrial downregulation RNAi was used to knockdown ant-1.1 in daf-2 loss of function leads to dramatic lifespan extension in the nematode (lf) mutants, followed by physiological assays to catalog the Caenorhabditiselegans. C.elegansshare83%proteomeorthology mutants’ ability to survive in a variety of stressors over time: with humans, providing potential insight about aging across oxidative stress, heat, and cold shock; we also tracked fat levels phyla. We previously observed a lifespan increase from 18 and food consumption with time. We measured worms on days to 90 days with the combination of two lifespan extending 1, 3, 5, 10, and 15 of adulthood (n > 100, 3 biological paradigms: downregulation of the worm orthologue for the replicates). Preliminary data suggest both daf-2lf and daf-2lf ant- insulin/insulin growth factor (IGF-1) daf-2 and knockdown of the 1.1 knockdown mutants have increased heat resistance and higher adenine translocase ant-1.1. daf-2 is involved in metabolism and fat retention; further data is being collected in all conditions. regulation of many aspects of worm physiology including lifespan, Successful completion of this project would provide a baseline for healthspan, reproduction, development, and stress resistance; understanding the mechanism underlying this lifespan extension. ant-1.1 moderates ATP flux through the mitochondria and has With these physiological data, we could know what systems also been implicated in lifespan extension. However, while this are intact versus impaired, suggesting further pathways to focus lifespan extension in the combined mutant has been observed, the mechanism and physiology of this extension are not well on. Future research would use RNA sequencing to determine a understood. comprehensive genetic profile of the mutated worms. Dissecting the Behavioral Effects of Neonicotinoid Exposure in Drosophila melanogaster Han Nguyen, Francesca Ponce, Benjamin de Bivort Harvard College | Pforzheimer House | Neuroscience | 2027 Neonicotinoid insecticides are widely used in agricultural and developed to compute turn bias, plot fly trajectories, and ensure urban environments and have been implicated in the decline compatibility with MARGO data formats. of insect populations. These compounds act on nicotinic acetylcholine receptors in the insect nervous system and can Preliminary results show little to no differences in turn bias disrupt behavior even at low, sublethal concentrations. This consistency or activity levels between exposed and control flies, suggesting that the tested concentration of imidacloprid may be project investigates the behavioral effects of chronic neonicotinoibelow the threshold needed to elicit detectable behavioral effects. exposure using Drosophila melanogaster as a model system. Ongoing work aims to test a wider range of concentrations Flies were chronically exposed to a single sublethal concentration to identify potential dose-dependent effects and determine the of imidacloprid, a commonly used neonicotinoid. A Y-maze minimum effective dose. Future directions also include finalizing assay was used to assess spontaneous turning behavior and behavioral quantification and incorporating neural imaging to locomotor activity, allowing for the quantification of exploratory better understand the relationship between pesticide exposure and decision-making. Control and exposed flies were tested under changes in neural circuitry. This work contributes to broader standardized conditions, and behavioral data were collected across efforts to characterize how environmental toxins affect insect multiple replicates. A custom Python-based analysis pipeline was behavior and informs ecological risk assessments of pesticide use.

Abstract:

Synergistic insulin signalling and mitochondrial downregulation RNAi was used to knockdown ant-1.1 in daf-2 loss of function leads to dramatic lifespan extension in the nematode (lf) mutants, followed by physiological assays to catalog the Caenorhabditiselegans. C.elegansshare83%proteomeorthology mutants’ ability to survive in a variety of stressors over time: with humans, providing potential insight about aging across oxidative stress, heat, and cold shock; we also tracked fat levels phyla. We previously observed a lifespan increase from 18 and food consumption with time. We measured worms on days to 90 days with the combination of two lifespan extending 1, 3, 5, 10, and 15 of adulthood (n > 100, 3 biological paradigms: downregulation of the worm orthologue for the replicates). Preliminary data suggest both daf-2lf and daf-2lf ant- insulin/insulin growth factor (IGF-1) daf-2 and knockdown of the 1.1 knockdown mutants have increased heat resistance and higher adenine translocase ant-1.1. daf-2 is involved in metabolism and fat retention; further data is being collected in all conditions. regulation of many aspects of worm physiology including lifespan, Successful completion of this project would provide a baseline for healthspan, reproduction, development, and stress resistance; understanding the mechanism underlying this lifespan extension. ant-1.1 moderates ATP flux through the mitochondria and has With these physiological data, we could know what systems also been implicated in lifespan extension. However, while this are intact versus impaired, suggesting further pathways to focus lifespan extension in the combined mutant has been observed, the mechanism and physiology of this extension are not well on. Future research would use RNA sequencing to determine a understood. comprehensive genetic profile of the mutated worms. Dissecting the Behavioral Effects of Neonicotinoid Exposure in Drosophila melanogaster Han Nguyen, Francesca Ponce, Benjamin de Bivort Harvard College | Pforzheimer House | Neuroscience | 2027 Neonicotinoid insecticides are widely used in agricultural and developed to compute turn bias, plot fly trajectories, and ensure urban environments and have been implicated in the decline compatibility with MARGO data formats. of insect populations. These compounds act on nicotinic acetylcholine receptors in the insect nervous system and can Preliminary results show little to no differences in turn bias disrupt behavior even at low, sublethal concentrations. This consistency or activity levels between exposed and control flies, suggesting that the tested concentration of imidacloprid may be project investigates the behavioral effects of chronic neonicotinoibelow the threshold needed to elicit detectable behavioral effects. exposure using Drosophila melanogaster as a model system. Ongoing work aims to test a wider range of concentrations Flies were chronically exposed to a single sublethal concentration to identify potential dose-dependent effects and determine the of imidacloprid, a commonly used neonicotinoid. A Y-maze minimum effective dose. Future directions also include finalizing assay was used to assess spontaneous turning behavior and behavioral quantification and incorporating neural imaging to locomotor activity, allowing for the quantification of exploratory better understand the relationship between pesticide exposure and decision-making. Control and exposed flies were tested under changes in neural circuitry. This work contributes to broader standardized conditions, and behavioral data were collected across efforts to characterize how environmental toxins affect insect multiple replicates. A custom Python-based analysis pipeline was behavior and informs ecological risk assessments of pesticide use.

Source:

Harvard / Harvard College | Kirkland House | Psychology | 2028 / 2025

Topics:

lifespan, extension, daf, behavioral, used, ant, mutant, worm, effect, fly, concentration, physiological

Co-authors:

@zoenathwani345 , @nicolestuhr346 , @sinclairemans347 , @alexsoukas348