Healthspan Pharmacology
The Jafari Lab aims to study and understand botanical extracts that extend lifespan and improve healthspan. Healthspan is a holistic measure of an organism’s life, encompassing not only lifespan but also other factors that more clearly define its state of health. In other words, it is the span of time an organism stays healthy, not just alive. Physiological functions including locomotor activity, cognitive ability, and reproductive fitness are typically measured as healthspan indicators. By examining healthspan, we can focus on finding pharmaceutical agents that length an organism’s lifespan without decreasing its quality of life. We believe that by slowing the aging process in this way, we can delay the progression of a number of age-related diseases such as Alzheimer’s disease or cardiovascular disease. Our ultimate goal is to add healthy, functional years to human life.
The fruit fly is a well-established model system for aging studies, and for good reasons. Its relatively short lifespan of ~90 days allows quick assaying of anti-aging pharmaceuticals. More importantly, fruit flies share about 75% of disease genes with humans, and about 50% of their protein sequences have mammalian homologs. Fruit fly models of human disease allow us to perform whole-organism studies and investigate many different aspects of physiology. These experiments serve as the necessary stepping stone to larger mammalian or clinical studies.
Healthspan Sciences
Over a course of 14 years evaluating a variety of botanical extracts and pharmaceutical agents for their anti-aging capabilities, we found botanical extracts to show the most promise. While some studies have shown that plants and botanical extracts such as Rhodiola Rosea and Rosa damascena may impact age-related diseases, there are large gaps in human knowledge about the mechanisms through which these natural products modulate aging. Our research hopes to bridge that gap and elucidate how botanical extracts affect the human body at a molecular level.
The “Golden Root” of Eastern Europe and Asia, Rhodiola Rosea has been traditionally used for its adaptogenic ability to relieve stress and fatigue. Our lab has discovered that it also boasts very robust anti-aging powers, extending the mean lifespan of male and female fruit flies by up to 25%. However, its molecular mechanism of action remains unclear. We continue to perform studies using Rhodiola Rosea in hopes of uncovering specifically how it delays the rate of aging, and how it can be used to remedy various age-related diseases.
OMIC-AI for Drug Discovery and Repurposing
Recent work with the model organism Drosophila has provided a new way to identify mechanisms of drug action in an effort to discover or repurpose therapeutics. Using multi-omics data generated from the impact of pharmaceuticals and natural products on phenotypes, transcriptomes, and metabolomics, we will validate the use of a novel platform for drug discovery using outbred populations of Drosophila. This work is a collaboration of research labs from the Department of Ecology and Evolutionary Biology (Mueller, Ranz and Rose laboratories) and Pharmaceutical Sciences (Jafari Laboratory). A powerful machine-learning tool called “FLAM” (for Fused Lasso Additive Models) that has shown success in parsing genome-wide differentiation to identify the causal links between omic differentiation and functional characters will be used to develop a drug discovery platform to identify new mechanisms of action of drugs and natural products. As a proof of concept, we are currently in the process of evaluating the impact of lithium on the transcriptome, the metabolome, and on functional assays in fruit flies. We chose lithium since lithium is a commonly used drug in psychiatric disorder without a well-established mechanism of action.