Executive Summary : | Advancements in science, technology, and healthcare have led to a significant increase in life expectancy, but this has also led to an increase in the aged population and associated disease burden. The elderly population in India is projected to double by 2050, making it crucial to develop interventions to limit diseases and infirmities associated with aging. An innovative strategy is to search for interventions that extend healthspan and delay the onset of ailments. Commensal microbiota and their metabolites indoles can extend healthspan across diverse species, as shown in Caenorhabditis elegans, Drosophila melanogaster, and mice treated with indoles. However, the role of indole in promoting healthspan is not yet known, and the longer generation time of mammals presents a primary roadblock in studying transgenerational phenotypes. To address this issue, a model organism, C. elegans, is proposed to investigate the transgenerational effects of indoles on healthspan. Indoles provide stress protection, extended healthspan across species, and influence epigenetic regulators implicated in transgenerational inheritance. Short chain fatty acids (SCFAs), another prominent class of metabolites produced by commensal microbiota, are also known to regulate epigenetic regulators and promote protein homeostasis, population growth, and energy. The project aims to assess the transgenerational healthspan effects of these molecules in C. elegans, building a foundation for developing commensal metabolites as therapeutics and enabling translational research to establish commensal metabolites as biomarkers to predict transgenerational healthy aging. |