Strategies for studying sex differences in brain aging

Understanding sex-based vulnerability or resilience in brain aging can reveal disease pathways and promote equitable treatments for sex-biased conditions. 

The Four Core Genotypes and XY* mouse models disentangle the specific roles of sex chromosomes and gonadal hormones, providing insights into sex specific brain aging.

Gonadectomy, depletion of endogenous estrogen, and the adult ovary to testis trans-differentiation mouse model help isolate effects of adult hormone exposure from early-life organizational and chromosomal effects.

Tractable high-throughput models, such as Caenorhabditis elegans, Drosophila, and African turquoise killifish (Nothobranchius furzeri) with shorter lifespans, conserved pathways, and sexually dimorphic phenotypes, can provide faster and unique insights into sex differences in aging.

Large-scale studies in humans for identifying epidemiologic associations and calculating brain-predicted age can provide evidence of sex differences in brain aging.

Integrating novel animal models with 'omics studies can help build gonadal and chromosomal regulatory networks, identify biological targets, and expand sex biology in aging studies.

https://www.cell.com/trends/genetics/fulltext/S0168-9525(25)00027-7

https://sciencemission.com/studying-sex-differences-in-brain-aging