Aging is the strongest risk factor for chronic disease, yet the biological mechanisms that drive systemic decline remain incompletely understood. Our laboratory’s experimental studies have shown that the hypothalamus, a central regulator of metabolism and endocrine function, plays a pivotal role in aging. Restoring hypothalamic stem cells or reducing hypothalamic inflammation can reverse age-associated metabolic and physiological decline in animal models, and these processes appear to be triggered by disruptions in lipid homeostasis.
The central research question of this project is whether hypothalamic structural integrity in humans is linked to systemic biological aging. Our primary objective is to determine whether hypothalamic atrophy, measured through MRI, predicts accelerated biological age as estimated by biomarker-based aging clocks. We will also test the hypothesis that hypothalamic structure mediates the relationship between systemic metabolic dysfunction and biological age, positioning the hypothalamus as a central node in the axis of aging.
A secondary objective is to identify modifiable factors that influence hypothalamic integrity and aging. By stratifying participants based on dietary intake, metabolomic, and proteomic profiles, we will explore which biological pathways and lifestyle factors are associated with hypothalamic decline. Longitudinal imaging data will allow us to examine whether hypothalamic changes over time predict faster aging trajectories. To ensure specificity, we will compare hypothalamic findings with structural changes in other brain regions.
By combining neuroimaging, clinical biomarkers, metabolomics, and dietary data, this project aims to provide population level evidence of hypothalamus axis of aging. The results could inform preventive strategies targeting hypothalamic health to mitigate functional decline and extend healthy lifespan.
