Approximately 60 Principal Investigators, and several Post Docs, both basic science/laboratory and clinical researchers, work within the Research Institute and the Medical Center.
California Pacific Medical Center physicians from many different disciplines engage in active research. Take a look at our Clinical Trials section for some of these projects.
Dr. Greg Tranah, and longevity research at CPMCRI
In this series on longevity research at California Pacific Medical Center Research Institute (CPMCRI) and the San Francisco Coordinating Center (SFCC), we profile a select group of researchers uncovering the genetic secrets of a long and healthy life. Having assembled a trove of longevity research, CPMC’s research institute is home to the largest, richest data sets about aging in the U.S. Age-related neurodegenerative illnesses including Alzheimer’s disease and dementia, and the physical decline associated with osteoporosis and osteoarthritis are being explored to uncover new targets for earlier prevention and even treatment. Using the latest tools in genetic sequencing and with sophisticated large-scale epidemiologic analyses, CPMCRI’s scientists are studying data on centenarians, and advancing the way we understand aging and long-term health. Experts in this area include Drs. Steve Cummings, Peggy Cawthon, Katie Stone, Greg Tranah, and Dan Evans.
Early clues in the onset of dementia and Alzheimer’s disease
First in this series on longevity research at CPMCRI, we profile Dr. Tranah, CPMCRI Scientist and Adjunct Professor in the Department of Epidemiology & Biostatistics at UCSF. Dr. Tranah is among a select group of researchers in the U.S. uncovering how alterations in mitochondrial DNA (mtDNA) can lead to cognitive decline, dementia, and Alzheimer’s disease, and how mitochondrial genetic variation plays a much greater role than once believed in neurodegeneration and age-related brain illnesses.
His latest findings—recently published in Neurobiology of Aging—explore these connections.
In the study, Dr. Tranah and colleagues assessed mtDNA sequence variations associated with the risk of dementia, 10-year cognitive changes, and markers of Alzheimer’s disease pathology (amyloid beta) in almost 2,000 African Americans. Study participants were over 70 years old and from the population-based Health, Aging, and Body Composition Study (Health ABC).
Those with mtDNA signatures common to Central and West African genetic ancestry (“Haplogroup L1”) had a significantly increased risk of dementia, experienced a significant 10-year decline in cognitive function (as assessed by the Digit Symbol Substitution Test), and had lower levels of protective amyloid beta plasma proteins compared with the most common African Haplogroups L2 and L3.
Current therapies for Alzheimer’s disease target end-stage illness and most only partially mitigate memory loss. Dysfunction of mitochondria—the energy producing powerhouses of our cells—is a hallmark of many neurodegenerative illnesses and represents a growing area of research. Dr. Tranah’s findings point to new pathways early in the progression of disease that may represent novel targets for more powerful therapies.
“We identified several inherited mitochondrial DNA mutations that predispose people to age-related cognitive decline, Alzheimer’s pathology, and dementia,” said Dr. Tranah. “These findings could revolutionize screening approaches to predict risk of dementia, and yield versatile, inexpensive tests to identify people who could benefit from existing pharmacologic and behavioral treatments that target mitochondria.”
“Additionally, identifying mitochondrial DNA variants associated with cognitive processes may yield new drugs or clinical strategies for maintaining neurologic function in the elderly.”
As follow-up to these findings, next year Dr. Tranah will study brain tissue samples isolated from patients with Alzheimer’s disease to determine mtDNA mutations implicated in pathogenesis of the illness. “Sequence variations in mitochondrial DNA may determine the levels of protective amyloid beta proteins in the brain,” said Dr. Tranah. “We hope to obtain a better understanding of the mechanisms leading to neurodegeneration so that the process can be targeted long before disease onset.”
Cognitive decline and dementia, largely in the form of Alzheimer’s disease, affects approximately 10% of adults over age 65, and rises to 50% of adults over age 85 in the U.S.
Read more about Dr. Tranah’s latest research.
- Peggy Cawthon
- Stewart Cooper, MD
- Steven Cummings, MD
- Shanaz Dairkee, PhD
- Robert Debs, MD
- Pierre Desprez, PhD
- Dan Evans, PhD
- Gantt Galloway, PharmD
- Mohammed Kashani-Sabet, MD
- Sean D. McAllister, PhD
- John Mendelson, MD
- John Muschler, PhD
- Karen L. Petersen, MD
- Michael C. Rowbotham, MD
- Minnie Sarwal, MD, PhD
- Tara Sigdel, PhD
- Liliana Soroceanu, MD, PhD
- Katie Stone, PhD
- Gregory James Tranah, PhD
- Cassandra Vieten, PhD
- Esther Wei, ScD
- Li Xi Yang, MD, PhD
- Garret L. Yount, PhD