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The Ghazi Lab - Molecular Genetics of Aging

The Ghazi Lab – Molecular Genetics of Aging

Aging is a universal phenomenon that is associated with many functional disabilities as well as susceptibility to diseases such as cancer, neurodegenerative ailments and diabetes. With a rapidly aging global population, it is a public health issue of great significance. Research on aging not only helps us understand a fundamental and fascinating biological process, but it may also be the least expensive and fastest path to simultaneously targeting multiple age-associated pathologies. Recent discoveries have suggested that aging is not just the result of stochastic cellular damage. Instead, it is strongly influenced by genes that appear to be conserved in their longevity functions, from worms to humans. Such longevity genes are the focus of our lab’s research.

ith a lifespan of only three weeks, C. elegans, helps the Ghazi Lab understand the genetics of aging. We study longevity genes in Caenorhabditis elegans, a model organism with a short lifespan of about three weeks. C. elegans displays many anatomical and functional changes that accompany human aging, as seen here in the scanning electron microscopy images of young and old C. elegans from our lab. Worm genes show strong homology with their human counterparts. Indeed, the most well known longevity pathway, the insulin/IGF1 signaling (IIS) cascade, was first identified for its role in aging in worms. Since then, many fundamental discoveries in the biology of aging have been made in C. elegans, and it continues to be a remarkably valuable system for aging research.

Our lab is especially interested in the relationship between reproduction and aging, and the genes that govern this complex interaction. Our recent studies have led us to focus on the role of three conserved, pro-longevity transcription factors and their roles in lipid-metabolism in governing the reproductive control of aging. These proteins (DAF-16, TCER-1, and NHR-49) appear to modulate lipid homeostasis by coordinately enhancing both lipid production and breakdown. Currently, we are investigating how lipid production and breakdown are coordinated and why this is important for health. Additional lab interests include the role of proteasomal protein degradation and miRNA pathways in aging.