Understanding Longevity: SIN-3 and DAF-16 Revealed as Independent Players in Lifespan Regulation

Abstract

Aging is the process of gradual physio-biochemical deterioration. While aging is inevitable, healthy aging is the key to individual and communal well-being. Therefore, it is essential to understand the regulation of aging. SIN-3/Sin3 is a unique regulatory protein that regulates aging without DNA binding activity. It functions by establishing multiple protein interactions. To understand the functional mechanism of this transcriptional regulator, the Caenorhabditis elegans protein interactome was assessed for SIN-3 interactions. DAF-16/FOXO emerged as one of the leading contenders for SIN-3-mediated regulation of aging. This study looks at the concerted role of SIN-3 and DAF-16 proteins in lifespan regulation. Phenotypic profiling for the mutants of these genes shows the functional accord between these two proteins with similar functions in stress response and vital biological processes. However, there were no significant physical interactions when checked for protein-protein interaction between SIN-3 and DAF-16 proteins. C. elegans genomics and transcriptomics data also indicated the possibilities of concerted gene regulation. This genetic regulation is more likely related to SIN-3 dominance on DAF-16 function. Overall, SIN-3 and DAF-16 proteins have strong functional interactions that ensure healthy aging. The influence of SIN-3 on DAF-16 mediated stress response is one of their convergence points in longevity regulation.