Strategies for studying sex differences in brain aging

Studying sex effects and their underlying mechanisms is of major relevance to understanding brain health. Despite growing interests, experimentally studying sex differences, particularly in the context of aging, remains challenging. Since sex chromosomal content influences gonadal development, separating the effects of gonadal hormones and chromosomal factors requires specific model systems. Here, we highlight rodent and tractable models for examining sex dimorphism in brain and cognitive aging. In addition, we discuss multi-omic and bioinformatic approaches that yield biological insights from animal and human studies. This review provides a comprehensive overview of the diverse toolkit now available to advance our understanding of sex differences in brain aging.