University of California, San Francisco (UCSF)

Protective Effects of Longevity Factor Klotho on Developing & Degenerating Brain

Research Area

Grant Type



The variation in each of our unique genetic codes globally impacts our individual process of aging. Our research focuses on identifying genetic contributions to healthy brain aging and neurodegenerative disease risk by studying how these genes are related to the brain’s structure and cognitive function. In research supported by a Hillblom Postdoctoral Fellowship, we previously identified variation in longevity factor KLOTHO that protects cognitive function and brain volume in aging adults. Complementary research has also shown that expressing higher levels of klotho can protect cognition in mouse models of Alzheimer’s disease. Our present project focuses on using genomicsand brain-imaging tools to understand how protective genetic variation affects the brain across the lifespan by studying the developing brain, healthy cognitive aging, and neurodegenerative disease. We have the following research objectives: First,we will elucidate the impact of protective KLOTHO variation on the brain during childhood and adolescence. Second, we will identify novel patterns of gene expression associated with healthy brain aging in a large elderly cohort previously funded through the Hillblom Foundation. Third, we will assess whether higher klotho protein levels in the body are associated with milder disease course in the context of neurodegeneration. The ultimate goal of this work is to identify genetic markers that promote healthy brain aging and can thus serve as novel therapeutic targets to treat age-related neurodegenerative disorders.