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The Healthy Aging Program

Rapamycin, Protein Homeostasis, and Aging

Principal Investigator: Viviana Perez, Ph.D.

My primary area of research interest is the role of protein homeostasis in longevity, using a comparative biology approach. We previously found that the proteomes of long-lived species like the little brown bat and naked mole rat are more resistant to urea- and heat-induced unfolding than those 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 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 or aggregation. My laboratory is focused on establishing the role of proteostasis control in longevity by studying three important processes that alter protein homeostasis: protein aggregation, protein folding (chaperones), and protein degradation.

My second area of interest includes studies on dietary restriction (DR) and rapamycin. Both interventions extend lifespan and healthspan in rodents, and previous data suggest that rapamycin could be acting in a similar way to DR. To test this, Iím developing a study involving four different feeding groups of mice: ad libitum, DR, rapamycin, and rapamycin-DR. If rapamycin acts like DR, DR should not have any additional effect on lifespan in the rapamycin- DR group. The outcome of this study may have a big impact on the aging field, providing a better understanding of and new insights into the aging process and new prospects for the development of DR mimetics.