Investigation of new tissue-specific mechanisms of aging control by caloric restriction in C. elegans

• Grant number: 19/04726-2
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2019
• Effective date (End): June 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Thiago Leite Knittel
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM

Abstract

There is a worldwide trend towards aging of the world's population, what gives rise to social, economic and public health issues. Caloric Restriction (CR) is an intervention that slows down the aging process in different species resulting in a reduction in the risk of age-related diseases. Aging and CR affect the cells of the organism in an indiscriminate manner. However, some cells seem to age faster or differently while others act in a determinant manner to coordinate organismal aging. Studying the casual relationships between tissue-specific alterations and aging is challenging in mammals and almost impossible in humans, what slows advances in this area of knowledge. Caenorhabditis elegans is a model that allows this kind of studies as it provides easy genetic manipulation, exhibits a short lifespan and age in a pattern that is similar to humans. With that in mind, we intend to isolate the main somatic tissues of C. elegans subjected to ad libitum diet or CR and analyze gene expression via RNA sequencing. We will identify genes that exhibit alterations with CR and select the ones that present similar changes in samples from mice and humans. We will then test their impact on the aging and CR phenotypes of C. elegans and their influence on the phenotypes of murine myoblasts and adipocytes. These experiments will allow the identification of new mechanisms of communication between tissues in the context of aging. These discoveries have the potential to inspire new drug targets. (AU)