Molecular Gerontology Research Group

Takuji Shirasawa, M.D., Ph.D.

Takahiko Shimizu,Ph.D., Midori Ogawara,Ph.D., Mayumi Takahashi,Ph.D., Eiko Moriizumi

Visiting Scientist :
Satoshi Uchiyama,Ph.D.

longevity, C. elegans, model mouse, insulin, daf-2, daf-16, clk-1, Alzheimer's disease, presenilin-1, amyloid- peptide, A-β

 We aim to resolve the mechanisms by which the lifespan is controlled in mammals and human. In C. elegans, several mutants that show longevity have been isolated and the genetic analysis in these mutant animals has suggested the involvement of insulin signaling pathway on the longevity. That is, genetic alterations were identified in the coding regions of the proteins transducing the insulin signal, such as insulin/IGF-1 receptor (daf-2) and PI3K (age-1). The involvement of mutations on another type of gene, clk-1, has also been suggested for longevity in C. elegans, which is independent on the insulin signaling. We have generated two types of model mice carrying the similar genetic alterations that were found in C. elegans (insulin/IGF-1 receptor knock-in mice and clk-1 knock-out mice). Utilizing these model mice, we are going to try to elucidate the mechanisms by which higher organisms succeed in longevity. In our group, the mechanisms underlying the development of Alzheimer's disease are also being studied.

1) Analysis of insulin receptor knock-in mice
2) Analysis of clk-1 knock-out mice
3) Analysis of aggregation properties of the modified β-amyloid proteins
4) Analysis of the biological functions of presenilin-1