Advanced age is the leading risk factor for developing Alzheimer’s and other neurodegenerative diseases. Evidence clearly shows that aging processes can be driven by DNA damage that results in mutations ranging from single base substitutions to large chromosomal alterations and aneuploidy (abnormal number of chromosomes). Such mutations accumulate during human aging at a higher frequency in brains affected by neurodegeneration. Cristina Montagna, Ph.D., and colleagues have recently shown that increased aneuploidy induces cellular senescence (i.e., cells permanently stop dividing but don’t die), which is now emerging as an important factor in age-related neurodegeneration. Clearance of senescent cells has yielded beneficial effects on various aspects of Alzheimer’s disease.
The NIH has awarded Dr. Montagna a five-year, $1.7 million grant to continue her research suggesting that large-scale genomic instability and aneuploidy accumulation in astrocytes and other non-neuronal brain cells may contribute to neurodegenerative diseases. For example, she and her colleagues will determine whether astrocytes made senescent due to genetic instability may contribute to neurodegeneration by failing to adequately nourish neurons. The researchers will also test two small molecules to determine their potential for killing astrocytes made senescent due to aneuploidy, thereby preventing the astrocytes from exerting harmful effects on neurons. These studies may reveal novel treatments for Alzheimer’s and other age-related dementias.
Dr. Montagna is an associate professor of genetics and of pathology at Einstein. Judith Campisi, Ph.D., of the Buck Institute and a member of Einstein’s Institute for Aging Research, is co-PI of the project. (1RF1AG068908)
Posted on: Wednesday, November 04, 2020