Molecular Biology of Aging

Research on aging is one of the main scientific challenges of the twenty-first century. The major reason for this is the continual increase in the average human lifespan. Our research aims to elucidate the mechanism of the molecular regulation of aging, and investigate two major pathways that have been shown to regulate lifespan - caloric restriction (CR) and Sirtuin deacetylases. CR has been shown to slow the rate of aging and extend the maximum lifespan of any organism in which it has been tested.  In rodents, a reduction of ~30% of the calorie intake imposes an increase of more than 30% in their lifespan. In addition, CR delays many age-related diseases such as cancer, diabetes, neurodegenerative and decline in the function of the immune system.  Although CR has been known for more than 70 years to extend lifespan, the molecular mechanism by which it retards aging and how it is regulated are still a speculation.

Studies in model organisms showed that the activity of the Sir2 family of
NAD+-dependent protein deacetylases (sirtuins) is important in regulating lifespan in yeast, worms, and flies. Overexpression of Sir2 in these organisms can extend their lifespan by ~40%, and in some yeast and fly strains, Sir2 mediates the effect of CR on lifespan. Moreover, we recently showed that in mammals, SIRT1, the closest human Sir2 homologue, is induced in multiple tissues upon CR and mediates the protection of CR from cell death.

Our current research focuses on the following topics:

1. The molecular pathways that regulate the response for caloric restriction.
2. The molecular and cellular biology of sirtuin deacetylases.
3. Isolating new proteins that regulate longevity in mammals.