Professors at Buck Institute, Judith Campisi PhD and Lisa Ellerby PhD have been granted the $14.3million grant by the NIH’s National Institute of Aging. This grant will enable them to examine cellular senescence as the main cause of Alzheimer’s disease and other age-related dementias.
“Age is the largest risk factor for Alzheimer’s disease and other dementias,” said Campisi, who is regarded as a pioneer in the study of the process of cellular senescence, which is a stress response which has been linked to a variety of diseases that are a result of aging. “We are very excited to apply our expertise in cell senescence to study the aging of the brain in the context of dementia. Our goal is to discover new mechanisms that could be used to treat patients.
Senescent cells spew out a panoply of inflammatory molecules (known collectively as the SASP – the senescence-associated secretory phenotype) that can have profound effects on tissue structure and function by promoting chronic low-level inflammation. Researchers who study the biology of aging are fascinated by the SASP. Many biotech companies are developing therapeutics to counter the harmful effects of senescent cell death.
There aren’t any effective ways to prevent or treat Alzheimer’s disease and other neurodegenerative diseases. This is the reason why there is a need to develop new strategies.
Judith Campisi, PhD, Professor, Buck Institute
An estimated 6.2 million Americans age 65 and older are currently living with dementia.
The five-year grant consists of three research projects, and it involves other Buck faculty. Campisi will lead the project that will examine in detail the senescent reactions of human and mouse microglia, astrocytes and neurons. Eric Verdin MD, President and CEO of Buck, will lead another project that will study changes in cellular and systemic metabolism and how they relate to inflammation, neurodegeneration, and other issues. Recent studies from the Verdin and Campisi labs shows that an increase in the burden of senescent cells triggers the degrading of NAD+ (nicotinamide adenine dinucleotide) which is a key metabolite that is essential to a healthy and healthy metabolism.
Lisa Ellerby will lead a third project that studies the SASP in connection with cell-cell interactions, especially between non-neuronal supporting cells in the brain. Buck research on mouse models of Parkinson’s disease as well as Huntington’s disease suggests that cellular Senescence plays a major role in the progression and pathology of these incurable neurodegenerative diseases. The senescent traits of Huntington’s disease neuronal cells is also present in Alzheimer’s. .
Ellerby a neuroscientist, who is co-principal investigator on the grant, will assist with the majority of the research. Her team will derive neurons, astrocytes, microglia and neurons from pluripotent stem cells that have been generated from all of the models utilized in the project, including those from patients with Alzheimer’s disease. Ellerby’s team will also create brain organoids. These are so-called “mini brains” which recreate the cellular structure, function, and the integrity of the brain. Ellerby explained that this will allow for three-dimensional research to track and understand the interactions of brain cells in complex environments. It will also let us “seed” organoids with cells that have senescence to observe what happens in real-time. This is a great time to begin this project because of the technological advances. Ellerby’s team will also be able develop cells that will repair the blood-brain barrier. This barrier has been a major hurdle in the development of treatments that reach the brain.
“This program is a quintessential example of the Buck’s strength,” said Verdin. It brings together researchers from diverse backgrounds and all of them are experts in modern age research and have a history of working together. I couldn’t be prouder of this team and I am thrilled that the NIH will be able to bring research on aging into combating Alzheimer’s disease as well as age-related dementia.
Content Source: https://www.news-medical.net/news/20210929/Buck-Institute-receives-2414-million-NIH-grant-to-focus-on-one-of-the-major-drivers-of-aging.aspx