Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
Biology and Bioengineering Division, Tianqiao and Chrissy Chen Institute of Neuroscience, California Institute of Technology, Pasadena, California, USA.
J Gerontol A Biol Sci Med Sci. 2024 Sep 1;79(9). doi: 10.1093/gerona/glae160.
Aging is the process of gradual physio-biochemical deterioration. Although 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/Sin-3 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 2 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.
衰老是一个渐进的生理生化恶化过程。尽管衰老是不可避免的，但健康衰老却是个体和社区福祉的关键。因此，了解衰老的调控机制至关重要。SIN-3/Sin-3 是一种独特的调节蛋白，它具有调节衰老的功能，而不具有 DNA 结合活性。它通过建立多种蛋白质相互作用来发挥作用。为了了解这个转录调节因子的功能机制，评估了秀丽隐杆线虫蛋白相互作用组中 SIN-3 的相互作用。DAF-16/FOXO 作为 SIN-3 介导的衰老调控的主要候选者之一出现。本研究探讨了 SIN-3 和 DAF-16 蛋白在寿命调控中的协同作用。这些基因的突变体表型分析表明，这两种蛋白在应激反应和重要的生命过程中具有相似的功能，它们的功能是一致的。然而，在检查 SIN-3 和 DAF-16 蛋白之间的蛋白质-蛋白质相互作用时，没有发现明显的物理相互作用。秀丽隐杆线虫基因组学和转录组学数据也表明了协同基因调控的可能性。这种遗传调控很可能与 SIN-3 对 DAF-16 功能的优势有关。总的来说，SIN-3 和 DAF-16 蛋白具有很强的功能相互作用，可确保健康衰老。SIN-3 对 DAF-16 介导的应激反应的影响是它们在长寿调控中趋同的一个点。
