Life Sciences & Biotechnology
Title : | Deciphering how RICTOR/TORC2 regulates one-carbon metabolism to modulate longevity depending on diet containing different Vitamin B12 content |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Arnab Mukhopadhyay, National Institute Of Immunology, New Delhi |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | arnab@nii.ac.in |
Details
Executive Summary : | The study focuses on understanding the role of diet and genes in determining life span. It uses C. elegans, a bacterivorous nematode, to study diet-gene interactions. The bacteria colonize the worm's gut, establishing a gut microbial system that affects metabolism, development, and longevity. A limited number of diet-gene pairs have been identified based on differential phenotypes, mostly on two commonly used bacterial feeds, E. coli HT115 and E. coli OP50. One such diet-gene pair was found when the flr-4 gene mutant showed a diet-responsive increase in life span, living longer on HT115 but not on OP50. This increased Vitamin B12 content in the bacteria, coupled with the increased sensitivity of the mutant to this micronutrient, engages the one-carbon cycle, leading to lower phosphatidylcholine levels that activate the p38 MAPK signaling pathway and the cytoprotective program required for extending life span. The study also found that another diet-gene pair comprising the conserved RICTOR/TORC2 complex genetically interacts with the flr-4 mutant. Preliminary data shows that the rictor mutant, which shows shorter life span on OP50 bacteria, can be rescued by supplementation of Vitamin B12. Based on this, the researchers hypothesize that RICTOR/TORC2 may regulate the One-carbon (1-C) cycle. The project will use molecular genetics and metabolomics of C. elegans to determine the mechanisms by which RICTOR/TORC2 regulates the 1-C cycle to mediate longevity regulation and whether such mechanism is conserved in mammalian cells. The study will provide valuable insight into this important regulatory pathway and have tremendous implications in our understanding of the functioning of the RICTOR/TORC2 complex in longevity, health, and disease. |
Co-PI: | Dr. Soumen Basak, National Institute Of Immunology, New Delhi-110067 |
Total Budget (INR): | 68,92,992 |
Organizations involved