The effect of germ cell depletion on health and life span
Class
Article
Department
Animal, Dairy, and Veterinary Sciences
Faculty Mentor
Jeffrey Mason
Presentation Type
Oral Presentation
Abstract
Changes in ovarian function at reproductive senescence increase disease risks in aged females. The incidence of pathological conditions normally associated with aging, such as cardiovascular disease and arthritis greatly increase in post-reproductive females. The onset of reproductive senescence has historically been attributed to the depletion of germ cells in the ovary. However, ovaries of post-menopausal women still contain germ cells. Prior work from our group indicates that, in post-reproductive mice, replacement of senescent ovaries with young ovaries increased life span and decreased cardiovascular disease, similar to the effects of dietary restriction and in non-mammalian species, to the effects of germ cell depletion. Germ cell ablation studies in Caenorhabditis elegans suggest key interactions between gonadal germ cells and somatic cells. In C. elegans, depletion of the entire gonad has no effect on life span, whereas removal of only the germ cells, while leaving the somatic cells intact leads to an increase in life and health span. Our hypothesis is that the influence of the young ovaries on increasing life span and promoting cardiac health in aged mice is mediated by germ-cell programming of ovarian somatic cells. We plan to test this hypothesis by using 4-vinylcyclohexene diepoxide (VCD) to deplete the germ cells of the ovary, and transplant germ-cell depleted ovaries to aged female mice, providing exposure to young ovarian somatic cells, but not germ cells. We expect to find that germ-cell depleted young ovaries will further extend life and health span. Preliminary results have shown that VCD significantly reduced primordial and primary ovarian follicles and induced an estropause-like state in young mice. Current experiments include analysis of germ-cell influenced changes in gene and protein expression. Knowledge from these experiments will elucidate the ovarian contributions to maintenance and extension of health span, which are specific to germ cells and to somatic cells.
Start Date
4-9-2015 11:00 AM
The effect of germ cell depletion on health and life span
Changes in ovarian function at reproductive senescence increase disease risks in aged females. The incidence of pathological conditions normally associated with aging, such as cardiovascular disease and arthritis greatly increase in post-reproductive females. The onset of reproductive senescence has historically been attributed to the depletion of germ cells in the ovary. However, ovaries of post-menopausal women still contain germ cells. Prior work from our group indicates that, in post-reproductive mice, replacement of senescent ovaries with young ovaries increased life span and decreased cardiovascular disease, similar to the effects of dietary restriction and in non-mammalian species, to the effects of germ cell depletion. Germ cell ablation studies in Caenorhabditis elegans suggest key interactions between gonadal germ cells and somatic cells. In C. elegans, depletion of the entire gonad has no effect on life span, whereas removal of only the germ cells, while leaving the somatic cells intact leads to an increase in life and health span. Our hypothesis is that the influence of the young ovaries on increasing life span and promoting cardiac health in aged mice is mediated by germ-cell programming of ovarian somatic cells. We plan to test this hypothesis by using 4-vinylcyclohexene diepoxide (VCD) to deplete the germ cells of the ovary, and transplant germ-cell depleted ovaries to aged female mice, providing exposure to young ovarian somatic cells, but not germ cells. We expect to find that germ-cell depleted young ovaries will further extend life and health span. Preliminary results have shown that VCD significantly reduced primordial and primary ovarian follicles and induced an estropause-like state in young mice. Current experiments include analysis of germ-cell influenced changes in gene and protein expression. Knowledge from these experiments will elucidate the ovarian contributions to maintenance and extension of health span, which are specific to germ cells and to somatic cells.