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The size of a cell's nucleolus may reveal how long that cell, or even the organism that cell belongs to, will live. Over the past few years, researchers have been piecing together an unexpected link between aging and an organelle typically known as the cell's ribosome factory (or perhaps just a blob in the middle of the nucleus). A May 17th review in the journal Trends in Cell Biology outlines the connections between the nucleolus and age-related pathways—such as those associated with dietary restriction or progeria.
"The nucleolus is perceived as a basic housekeeper: It's responsible for producing ribosomal RNA, which is important for the synthesis of proteins that are essential to the vitality of the cell," says Adam Antebi, director of the Max Planck Institute for Biology of Ageing in Germany, who co-authored the review with postdoctoral fellow Varnesh Tiku. "But our work and other people's work shows that the nucleolus plays many different roles, including lifespan control."
Studies - Nucleolus - Yeast - Worms - Fruit
Studies of aging and the nucleolus have been carried out in yeast, worms, fruit flies, mice, as well as early data in humans undergoing dietary restriction and exercise. Worms are particularly useful for aging research because they only live for about a month, so it's possible to tweak their genomes and see what extends or shortens their lifespans. Antebi and others have seen that common pathways related to aging ultimately affect nucleolar size—organisms with enlarged nucleoli have shorter lifespans and those with shrunken nucleoli have longer lifespans.
Many of these longevity pathways converge on a nucleolar regulating gene called NCL-1. Dietary restriction, reduced insulin signaling, and other lifespan-extending interventions increase the activity of NCL-1, reducing nucleolar size and the creation of ribosomes. Worms lacking NCL-1 receive no age-extending benefits from these therapies. Relatedly, people with diseases such as cancer or progeria that accelerated aging...
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