Two professors at the Buck Institute for Research on Aging in Novato have been awarded a $14.3 million grant to look for connections between aging cells and age-related dementias such as Alzheimer’s disease.
The National Institutes of Health awarded the funds to Judith Campisi, a specialist in cellular senescence, and Lisa Ellerby, an expert on cell death in neurodegenerative disorders such as Huntington’s disease.
Senescence refers to a process by which aging cells stop dividing but do not die.
“We are extremely excited to bring our expertise in cellular senescence to efforts to study brain aging in the context of dementia,” Campisi said. “Our objective is to uncover new mechanisms that can be developed into interventions to treat patients.”
Much of the Buck center’s research over the years has sought to better understand and find treatments for Alzheimer’s. The institute’s mission is to study the mechanisms of aging and to identify therapeutics that will allow people to live longer while remaining healthy. It’s estimated that some 6.2 million people ages 65 and older in the United States are living with dementia.
In 2018, Campisi was elected to the National Academy of Sciences for her pioneering work on cellular senescence. Initially, Campisi’s studies at Boston University Medical School had nothing to do with aging. She pursued it as a novel avenue for cancer research, because cancers are suppressed when cells can no longer divide.
Many researchers tried to establish a link between aging and the fact that senescent cells stop dividing. They suspected that secretions from the senescent cells stopped the cells from dividing.
Campisi’s insight was that secretions on surrounding tissue was the link to aging. In papers published in Cell and the Journal of the American Geriatrics Society in 1996 and 1997, Campisi presented research showing that senescent cells broadcast a panoply of inflammatory molecules that can have profound effects on surrounding tissue by promoting chronic, low-level inflammation.
The research projects funded by the new grant will seek to establish links between the secretions from senescent cells and dementias.
“This is a new concept,” Campisi said. “We’re not going to focus on the amyloid beta plaques and tau tangles. We’re going to be looking at cellular states.”
The research will be conducted using tissue from mice and humans. Some of the human tissue will be generated using stem cells and some will come from cadavers.
Campisi said the research will also involve the growing of brain organoids, “which is close as we can come to building a human brain.”
“We can take several cell types that are present in the brain,” she said, “and build three-dimensional structures that mimic how these cells talk to each other inside the brain.”
Much of this work will call on the expertise of Ellerby, a neuroscientist.
“It will also allow us to ‘seed’ these organoids with senescent cells to see what happens in real time,” Ellerby said. “The advances in technology make this a really exciting time to embark on this project.”
Campisi said the use of human tissue is crucial for making discoveries that will lead to therapeutics.
“In the end a mouse is a mouse and a human is a human,” she said.