Characterization of the Tissue-Specific Role of the Argonaute ALG-1 in Aging, Stress Response, and Cuticle Integrity in C. elegans.

• Grant number: 24/18680-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Talita Cristina Mena Segato
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process, AP.TEM

Abstract

Aging is a natural process that occurs across species, leading to a decline in adaptive homeostasis and reducing the organism's resistance to stressors, increasing the risk of chronic or infectious diseases. Caenorhabditis elegans is a model organism that facilitates experimental studies of aging due to its transparency, short lifespan, and ease of genetic manipulation. This organism has a physical barrier known as the cuticle, which is important for maintaining its integrity and viability. Over time, the cuticle may lose its structural and functional characteristics during aging. In C. elegans, the protein ALG-1 (encoded by the alg-1 gene, homologous to the human AGO2 gene) is part of the Argonaute family of proteins, which participate in post-transcriptional gene silencing through their critical role in microRNA (miRNA) biogenesis and function. Both ALG-1 and miRNAs decrease in abundance with aging and are essential for lifespan regulation and stress response. One way to evaluate the tissue-specific role of miRNAs is through the inhibition of ALG-1 in specific tissues using a combination of techniques such as SKI LODGE (Single-copy Knock-In Loci for Defined Gene Expression) and AID (Auxin-Inducible Degron). In preliminary studies using C. elegans models of tissue-specific ALG-1 loss-of-function generated by these methodologies, it was observed that the degradation of ALG-1 in the hypodermis is sufficient to decrease oxidative stress resistance and reduce the lifespan of the worms. Since this tissue plays a crucial role in maintaining the cuticle, in this project, we aim to further investigate the relationship between ALG-1 and cuticle integrity and how this is connected to the aging process and response to stressors.