Women live longer than men in almost every country, yet they are more likely to spend later life with disability, dementia and other chronic conditions. This paradox has challenged scientists for decades: survival alone does not explain how biological aging unfolds, why some diseases affect women and men differently, or why longer life does not always translate into more years of good health. A new $7.5 million, five-year grant from the National Institutes of Health is now funding a major effort to investigate those differences and transform them into practical strategies for healthier aging.
The grant will establish the USC Geroscience Specialized Center of Research Excellence on Sex Differences in Aging, known as GeroSCORE, at the University of Southern California’s Leonard Davis School of Gerontology. The center is USC’s first NIH Specialized Center of Research Excellence, or SCORE, and is supported by the National Institute on Aging in partnership with the NIH Office of Research on Women’s Health. Its investigators will examine how sex-related biology interacts with genes, hormones, behavior and social and physical environments across the entire life course.
The scientific problem is more complex than comparing men and women as two fixed categories. Aging is shaped by interacting biological systems, including immune function, metabolism, hormone signaling, brain health and cellular repair. These systems are also influenced by education, income, work, stress, caregiving, health care access and exposure to pollution or other environmental hazards. GeroSCORE will bring together specialists in geroscience, neuroscience, psychology, epidemiology, demography, sociology and data science to study these factors as connected components of aging rather than isolated explanations.
“Women and men age differently; the challenge is understanding why,” said Jennifer Ailshire, UPS Foundation Chair at USC Leonard Davis and one of the center’s directors. Researchers will use the center to connect evidence from laboratory models with information collected from human participants and large population studies. This approach could reveal why the same biological process produces different outcomes depending on sex, life stage or social context. It may also help explain why women are more likely to develop Alzheimer’s disease and certain disabilities despite generally outliving men.
One project, led by associate professor Bérénice Benayoun, will focus on menopause and brain aging. Menopause is accompanied by major changes in ovarian hormone levels, particularly estrogen, but its effects on the brain remain difficult to study in conventional animal models. Benayoun’s team will use a novel model designed to more closely reproduce the human menopausal transition. By tracking changes in brain cells, molecular pathways and behavior, the researchers hope to determine how reproductive aging affects neural resilience and whether the transition creates opportunities for early intervention.
Another project, led by Teal Eich, will investigate the biological pathways connecting neuroendocrine aging with Alzheimer’s disease risk. The study will combine neuroimaging, cognitive testing, hormone measurements and other biomarkers. Neuroimaging can reveal changes in brain structure and function before symptoms become obvious, while blood or other biological markers may indicate inflammation, hormonal disruption or neuronal injury. Integrating these measurements could show whether age-related hormonal changes influence cognitive decline directly, indirectly through vascular or metabolic pathways, or in combination with other risk factors.
A third research program will use large population datasets to explore how genetic, environmental and social exposures shape health differently across the life course. Eric Klopack, an adjunct assistant professor at USC Leonard Davis and an assistant professor of epidemiology and biostatistics at Indiana University, will lead the project in collaboration with Ailshire and USC University Professor Eileen Crimmins. The investigators will examine how inherited traits interact with experiences such as childhood conditions, neighborhood environments, education, stress and access to medical care. Statistical models can then identify whether particular exposures have stronger or weaker effects at different ages or in different sex groups.
This population-level work is especially important because biological differences do not operate independently of social conditions. A person’s cumulative exposure to disadvantage can influence inflammation, cardiovascular health, cognitive aging and the pace of biological decline. At the same time, social roles and health behaviors may change how disease is detected, treated or managed. By linking demographic information with genetic and physiological data, GeroSCORE researchers aim to distinguish mechanisms rooted in biology from differences produced or amplified by the environments in which people live.
The center will not only conduct its own studies. It will develop shared analytical tools, scientific resources and research methods for investigators studying sex differences in aging across the United States and internationally. GeroSCORE will support pilot projects, train early-career scientists, organize meetings with national and global experts and collaborate with other centers in the NIH SCORE network. The organizers say these activities are intended to reduce fragmentation in the field, where researchers often use different definitions, measurements and analytical approaches that make findings difficult to compare.
The ultimate goal is to identify pathways that can be targeted before disease becomes disabling. If researchers can determine how menopause affects brain aging, how hormones interact with Alzheimer’s risk or how social exposures alter biological resilience, clinicians may eventually be able to design prevention programs tailored to different life stages and risk profiles. “Scientific progress depends on more than individual discoveries,” said Crimmins, AARP Chair in Gerontology and a GeroSCORE co-director. By building a national research community around sex differences, USC scientists hope to convert a longstanding demographic paradox into better interventions, greater independence and more healthy years of life for everyone.
Subject of Research: Sex differences in aging, geroscience, menopause, brain aging, Alzheimer’s disease risk, genetics, hormones, social and environmental exposures, and healthy longevity.
Article Title: USC Launches $7.5 Million Center to Investigate Why Women and Men Age Differently
Web References:
https://gero.usc.edu/
https://www.nia.nih.gov/
https://orwh.od.nih.gov/
https://orwh.od.nih.gov/womens-health-research/funded-research-and-programs/score
https://gero.usc.edu/faculty/ailshire/
https://gero.usc.edu/faculty/berenice-benayoun-phd/
https://gero.usc.edu/faculty/teal-s-eich-phd/
https://gero.usc.edu/faculty/eric-klopack-phd/
https://gero.usc.edu/faculty/crimmins/
References: National Institutes of Health; National Institute on Aging; NIH Office of Research on Women’s Health; USC Leonard Davis School of Gerontology.
Keywords: Sex differences in aging, gerontology, geroscience, healthy aging, older adults, aging populations, human health, human physiology, public health, demography, neuroscience, epidemiology, Alzheimer’s disease, menopause, brain aging.
Tags: biological mechanisms of agingbiology of aging and sexchronic conditions in older womengender disparities in health and longevitygender-based health disparitiesgender-specific disease riskhealth strategies for aging populationsNIH-funded aging researchsex differences in agingsex hormones and genetics in agingsocial and environmental influences on agingUSC Geroscience Center
