Supporting Healthy Aging with a Phytochemical Combination that Acts at Multiple Control Points in the Nrf Activation Pathway

The average lifespan and the number of older individuals is increasing in the US but because age is a primary risk factor for most chronic disease there is an accompanying increase in the burden of chronic disease in the US Diet and lifestyle choices including dietary supplementation may be useful approaches to slowing the aging process and increasing healthspan and also may be the best strategy for minimizing the burden of many chronic diseases One promising approach to supporting healthy aging is protecting the body by inducing upregulation of its own cell survival genes through dietary supplementation with phytochemical combinations that activate the Nrf NFE L Nuclear Factor Erythroid Like cell signaling pathway At Pathways Bioscience we are developing a dietary supplement combination PB that synergistically activates the Nrf cell signaling pathway which in turn upregulates antioxidant anti inflammatory and other cell protective genes and is a promising candidate for improving health status during aging The phytochemicals in PB were specifically selected because they act at different control points on the Nrf activation pathway so that small amounts of each are able to work synergistically together to create relevant Nrf activation responses and gene expression This is an innovative approach being developed by Pathways Bioscience Our preliminary data indicates that the active components of PB upregulate Nrf signaling and the expression of Nrf dependent genes more than two fold higher than would be predicted by the adding the responses of each agent individually that dietary PB in mice increases liver catalase activity and Nrf dependent HMOX gene expression and decreases markers of inflammation in cultured mouse macrophages In this project we will expand upon the preliminary data to create an optimized ratio of active components and test the PB dietary supplement in vivo in a mouse model of aging based on the measurement of protein homeostasis proteostasis which refers to cellular control of the concentration location and conformation of individual proteins to achieve stability The ability to maintain proteostasis is a key outcome in aging and chronic disease research This makes deficiencies in proteostasis a biomarker associated with aging and also a target for anti aging strategies such as PB induced Nrf activation Age is a primary risk factor for most chronic diseases Therefore research into ways to slow the aging process is an area of great importance to both individuals and society in general In the current project we are developing a new dietary supplement product that acts at the gene regulation level to increase the bodyandapos s own cell protective mechanisms and support healthy aging