What do we study?
We study the biology of aging, longevity, and diseases of the aging brain, including Alzheimer’s and Parkinson’s diseases. Because aging is the greatest risk factor for neurodegenerative disease, we ask a fundamental question: Can we harness mechanisms of longevity and resilience to protect the brain from aging and disease?
Our research focuses on longevity factors, sex chromosomes, hormones, and sex-specific biology to discover new ways to preserve cognition, prevent neurodegenerative disease, and advance brain health for women and men.
Why do we study aging and diseases of the aging brain?
As the world’s population ages, cognitive decline and neurodegenerative diseases pose growing threats to human health. Yet some individuals maintain remarkable cognitive function despite aging or brain pathology. Women live longer than men but face a disproportionate burden of Alzheimer’s disease.
Understanding the biological mechanisms of longevity, cognitive resilience, and sex differences may reveal new ways to prevent disease and promote healthy brain aging.
How do we study aging and disease?
We investigate aging and brain disease from molecules and cells to neural circuits and cognition. Our research combines mouse models, molecular genetics, genomics, epigenetics, and neuroscience with studies of human cognition, brain imaging, biomarkers, and brain tissue.
By integrating fundamental discoveries with human biology, we aim to identify new mechanisms and therapeutic strategies to protect the aging brain.
What have we discovered?
Our laboratory has made foundational discoveries in two major areas of aging biology.
Sex chromosomes regulate longevity, brain aging, and cognition.
Our research established that XX sex chromosomes promote longevity and that the parental origin of the X chromosome influences brain aging. We further discovered that aging awakens genes on the silent X chromosome and can these be harnessed to improve cognition in the female – and male – brain.These discoveries reveal fundamental roles for sex chromosomes in brain resilience and open new avenues for understanding sex differences in aging, Alzheimer’s disease, and women’s brain health. Our recent perspectives and reviews in JAMA, Neuron and Science explore the broader implications of female biology for women’s health in aging and disease.
The longevity factor klotho enhances cognition and brain resilience.
We pioneered the discovery that klotho enhances cognition and protects against cognitive deficits in models of Alzheimer’s disease. We subsequently demonstrated that systemic klotho treatment improves brain function, including in aged nonhuman primates.Our research also identified platelet factor 4 (PF4) as a mediator of cognitive enhancement and revealed protective effects of klotho on cognition in Parkinson’s disease.
Together, these discoveries demonstrate the potential of targeting longevity biology to enhance cognition and protect against neurodegenerative disease. These discoveries are now advancing toward human clinical trials to test if klotho can improve cognition in neurodegenerative disease.
Key questions we are investigating
- How do longevity mechanisms protect the aging brain? Can factors such as klotho enhance cognition and prevent neurodegenerative disease?
- How do sex chromosomes influence longevity and brain aging? Can we harness X chromosome biology to improve resilience?
- What makes the female brain unique? How do sex chromosomes and hormones shape women’s brain health, aging, and disease?
- What makes the male brain unique? How do factors secreted by the testes and genes on the Y chromosome influence longevity, brain aging, and neurodegenerative disease?
- Why are some brains resilient to aging and disease? Can we identify and activate mechanisms that preserve cognition?
- Can discoveries lead to new treatments? Can we translate longevity and sex biology into therapies that improve brain health for women and men?