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Orthotopic Ovarian Transplantation Procedures to Investigate the Life- and Health-span Influence of Ovarian Senescence in Female Mice
Published on: February 12, 2018
Young Ovary Factors Transfer Female Cognitive Resilience to the Aged Male Brain
Abstract:
Women typically exhibit slower age-associated cognitive decline than men. Here, we show that young ovary-derived blood factors transfer female cognitive resilience to the aged male brain. Administration of young female-derived blood plasma elicited greater cognitive and neurogenic enhancements in aged male recipient mice compared to young male-derived plasma. Heterochronic young ovary transplantation likewise boosted cognition, neurogenesis and synaptic-related transcriptional signatures in aged males. We identify secreted frizzled-related protein 4 (SFRP4) as an ovary-enriched circulating factor in young female plasma, of which systemic elevation in aged male mice ameliorates cognitive impairments. Mechanistically, we identify bone-derived pro-youthful factor osteocalcin as a downstream peripheral mediator of SFRP4-induced cognitive benefits. Together, these findings highlight an ovary-bone-brain axis through which blood factors confer female cognitive resilience in aging.
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