Biology of Sex differences in Aging and organ functions (BioSAge)

Post Date: October 21, 2026

Expiration Date: October 21, 2028

This topic encourages a broad range of studies aimed at identifying and elucidating the mechanisms underlying sex differences in organ function across multiple organ systems, with the goal of improving healthspan and longevity in older adults. Research proposed for this topic may include novel investigations or analyzing existing large datasets to systematically examine sex differences and determine how genetic, epigenetic, hormonal, and non-hormonal factors influence tissue physiology and age-related diseases. Approaches may incorporate a variety of potential models — including animals, in vitro, in chemico, and in silico systems—as well as human tissue samples and data from established and publicly available cohorts.

Biological sex is a key modifier of mortality and morbidity, profoundly influencing physiology and disease. Many chronic conditions that drive U.S. healthcare costs—such as cancer, cardiovascular disease, diabetes, osteoarthritis, autoimmune disorders, and Alzheimer’s disease—disproportionately affect women. While men live, on average, five fewer years than women, women more often experience multiple chronic conditions that significantly diminish their quality of life for more years than men. On the other hand, men suffer higher rates of premature mortality and are more likely to die from acute conditions such as heart disease and injuries at younger ages. As a result, more research is needed to better understand the biological mechanisms underlying these sex-based differences in disease risk, progression, and outcomes, and to inform more tailored and effective prevention and treatment strategies for both men and women.

Recognizing sex as a critical biological variable,  NIH convened a workshop, Sex Differences Impacting Human Health Across the Lifespan, to assess the current state of the science and identify unmet research needs and promising opportunities. The workshop underscored the importance of understanding sex-specific mechanisms across cells, tissues and organ systems to enable more targeted therapeutic development, to delay, reduce or prevent functional decline, and accelerate clinical trial design to improve long-term health outcomes and extend healthspan. This topic encourages applications seeking to understand the molecular mechanisms responsible for, and the physiological implications of these differences to sex specific healthspan.