Aneuploidy and Aging

Aneuploidy is the state in which a cell has an abnormal number of chromosomes and is dysfunctional as a result. Like all forms of cellular malfunction, there is more of it in old tissues. But is it significant in aging? In recent years researchers demonstrated that one way of reducing aneuploidy is to boost levels of BubR1, which normally declines with age. As a genetic alteration this extends life in mice, but of course has a range of other effects beyond influencing aneuploidy, so the meaningful mechanism in this extension of healthy life isn't clearly defined. This is the case for many ways to slow aging in mice. Here is a piece on another group studying aneuploidy in aging:

Dr. Dunham has recently focused her efforts on the role of aneuploidy in aging. In the last few years, her lab has generated disomic yeast strains, in which each individual chromosome is duplicated, for all the yeast chromosomes (yeast are haploid organisms and normally only have one set of chromosomes). Interestingly, she found that strains with individually duplicated chromosomes had a dramatic decrease in replicative lifespan. Furthermore, her lab identified a suppressor mutation that rescued lifespan decline in these strains. The suppressor mutation was a missense mutation in Bul1, which is part of the Rsp5 E3-ubiquitin ligase complex and is involved in protein quality control. This finding supports a potential mechanism by which aneuploidy effects aging via perturbing protein quality control.

"My lab has already developed tools for studying aneuploidy using genomics and genetics, and the aging phenotype is just another interesting phenotype that we could apply our suite of existing tools too. I've always been interested in aging. I did a rotation in an aging genetics lab in graduate school. What I like about the aging field also is that so much fundamental biology is touched on by aging. And I really like studying metabolism. If you ask who is still interested in studying metabolism...the answer is the aging people! They get that metabolism is really cool and fundamental! I am interested in what happens in general when you have the wrong number of chromosomes: what things go right, and what things go wrong? Can cells tolerate it, and how do they do so if they can? I think that aging is a good phenotype because it's another aspect of what the cell has to do. Being able to look at a cell from birth to death and across environments and phenotypes and determine where aneuploidy and DNA copy number variation can have an effect, this is just one piece of that."



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