Nathan D McCoy, Steven P. Gawrys, Samuel G. Mackintosh, Stephanie D. Byrum, Negar Kosari, Anhong Zhou, Mishfak A. M. Mansoor, Yuji Ikeno, José V. V. Isola, Michael B. Stout, Augusto Schneider, Michał M. Masternak, Jeffrey B. Mason
Women experience more pronounced lipidomic changes with aging than men, which may contribute to the higher rates of Alzheimer's disease seen in postmenopausal women. Our earlier findings showed that transplantation of young ovarian somatic tissues or cells produced positive health-enhancing results in postreproductive females. In the current experiments, we looked to find key health-enhancing ovarian cells and pathways involved in this phenomenon. We conducted physiological and molecular analysis on animals/samples from old, postreproductive mice that received young ovarian tissue/cell transplants. Our analysis revealed a loss with age and a restoration with ovarian tissue/cell exposure, of serum biomarkers of lipid signaling and histological and behavioral markers of cognitive function. We further found, with single-cell transcriptomics and Raman spectroscopy, two candidate ovarian somatic cell types implicated in the restoration of health through a lipid signaling-based process. These results have identified key factors toward the determination of how germ cell-independent ovarian somatic tissues restore health through regulation of lipid signaling and dementia in postreproductive female mice.