Current research in the Gaurente Lab with mice is aimed at two general areas. First, we are interested in determining whether SIR2 is a regulator of longevity in mammals. We are also studying the function of RecQ-family members in mice.

Mouse SIR2 homologs and aging

Based on the discrovery that SIR2 is a key regulator of longevity in both yeast and worms, we are interested in determining whether this conservation of function also extends to mammals. The mouse offers a good experimental organism to test this hypothesis. There are 7 SIR2-family members in mice and we are in the process of generating knock-out and knock-in mice for several of them. The Guarente Lab SIR2 Mouse Group includes Namjin Chung, Ethan Ford, Beatrice Jegalian, Shin Imai, and Maria Carle Motta.

Mouse RecQ homologs and aging

Mutation of the RecQ homolog WRN results in the human disease Werner Syndrome. Mutation of the mouse Wrn homolog has no obvious phenotypic defect (See Lombard et al., 2000). One possibility is that RecQ-family members may be able to compensate for each other in mice to a larger extent than in humans. Another possibility is that because mouse telomeres are much longer than human telomeres, the most severe defects associated with loss of WRN may not be apparent in mice. To address this, Brad Johnson is attempting to generate mice that are homozygous for mutations in two RecQ homologs mWRN and mBLM as well as mouse telomerase.