This proposal entitled """"""""Senescence-specific promoter vectors"""""""" is being submitted in response to PA number- PAR-98-021 and falls under the research objectives category of """"""""Gene expression vectors"""""""". I am a new principal investigator in the field of aging. Aging is a complex phenomenon that occurs at every level, from molecular to organismic level. At the cellular level, aging is defined as a limited cell division potential of the cells. This property is also known as replicative senescence or finite replicative life span. Replicative senescence is believed to play an important role in organismic aging, particularly the aging of mitotic tissues in an organism. It also contributes to the development of various age related pathologies. Recently, few genes that are differentially expressed during replicative senescence have been cloned. In addition, there are other known genes that are suspected of playing a role in aging. The exact function of these genes in replicative senescence and in vivo aging is not well understood, partly because of the lack of molecular tools.
The aim of this proposal is to isolate senescence-specific regulatory sequences using a novel approach known as promoter trapping. These senescence-specific regulatory sequences will then be used to construct gene expression vectors, which will confer senescence- and age-specific expression to a heterologous gene. The senescence-specific promoter vectors will be used to test the role of various genes, such as enzymes involved in oxidative metabolism, growth hormone, insulin like growth factors, Werner and Bloom syndrome helicases and telomerase genes in tissue culture studies. Similarly, these vectors could be used to express the above candidate genes in transgenic animals. The senescence- specific promoter vectors, thus, will be useful not only to test he function of individual genes in vitro but also in vivo studies and provide tools to test the various hypotheses of aging, such as oxidative damage, DNA repair deficiencies, hormonal imbalance and telomere erosion etc.
