Female aging: when translational models don't translate

Area of Science:

• Gerontology
• Reproductive Biology
• Preclinical Research Models

Background:

• Female patients exhibit higher morbidity and adverse treatment events in aging-associated pathologies compared to males.
• Current preclinical aging models inadequately represent female aging trajectories, particularly reproductive senescence.
• Less than 1% of aging biology research includes menopausal phenotypes, despite reproductive senescence influencing over 70% of top age-related diseases.

Purpose of the Study:

• To summarize limitations in commonly used preclinical aging models regarding female biology.
• To provide recommendations for integrating menopause, pregnancy, and sex considerations into aging research.
• To outline actionable steps for researchers, journals, funding agencies, and animal providers to address these gaps.

Main Methods:

• Literature review and analysis of current preclinical aging models.
• Identification of key omissions in aging research concerning female reproductive physiology.
• Development of recommendations and action items for improving sex inclusivity in aging studies.

Main Results:

• Prevalent aging models fail to incorporate crucial aspects of female aging, such as menopausal transitions and the impacts of pregnancy, birthing, and breastfeeding.
• This omission leads to a significant knowledge gap in understanding age-related diseases in females.
• Existing research predominantly utilizes models that do not reflect the biological realities of female aging.

Conclusions:

• There is a critical need to enhance preclinical aging models to accurately reflect female aging trajectories, including reproductive factors.
• Implementing recommendations for incorporating sex-specific considerations is essential for advancing aging biology and improving health outcomes for women.
• A collaborative effort involving researchers, institutions, and funding bodies is required to address the underrepresentation of female aging phenotypes in research.