My primary research focus is investigation of the role of protein homeostasis in aging. Studies in mice, Drosophila and C. elegans suggest that activities associated with protein homeostasis decrease during aging. Previously in our laboratory, we found that the proteomes of long-lived species (i.e., little brown bat and naked mole rat) are more resistant to both urea-induced and heat-induced unfolding than that of shorter-lived bats or mice. We have also shown more robust maintenance of the proteasome and lower levels of ubiquitinated proteins in old (20-yr) naked mole rats when compared to old (3-yr) mice, suggesting that long-lived species might have evolved enhanced chaperone-like activities to preserve protein structure and prevent misfolding/aggregation. Using a comparative biology approach, my laboratory investigates the role of proteostasis in longevity by studying the three important processes that affect protein homeostasis: protein aggregation; protein folding (chaperones); and protein degradation.
My second area of interest includes studies on dietary restriction and rapamycin. The rationale for this study is that both interventions extend lifespan in rodents, and previous data suggest that dietary restriction and rapamycin could be acting via similar mechanisms. To test this, I am developing a study that compares the lifespan of mice maintained under four conditions: ad libitum feeding; dietary restriction; ad libitum feeding plus rapamycin; dietary restriction plus rapamycin. If rapamycin and dietary restriction act via the same mechanism, the effects of dietary restriction and rapamycin on lifespan should not be additive. If this is found to be the case, it will have a big impact on the aging field. It will provide a better understanding of the aging process, spur the development of caloric restriction mimetics, and generate new insights regarding human aging.
