Friday, 19 April 2013

Researchers discover stem cell senescence is linked to aging

As animals age, humans included, the levels of the "Mitotic checkpoint serine/threonine-protein kinase BUB1 beta" protein (BubR1) drop. Past studies, clearly show that declined BubR1 levels are associated with cell senescence (ageing), weight loss, muscle atrophy and cataracts. Now, a new study by researchers at the Mayo Clinic sheds new light in how stem cell senescence is linked to BubR1 decline and how age-related tissue deterioration may be partially reversed by removing stem cells affected by the BubR1 protein.

BubR1 is an enzyme that is crucial for mitosis, the process by which a cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. Insufficient BubR1 levels cause chromosomal imbalance, leading to premature ageing and even tumorigenic activity, while studies on mice have showed that increased expression of BubR1 extends their lifespan.



During mitosis the chromosomes of a cell nucleus are divided


In this study, the researchers used a strain of mice that expressed low levels of BubR1. During their experiments, they noticed the development of dysfunctional skeletal, muscle, fat and lens tissue with impaired cell regeneration. Further analysis revealed that a few stem cell populations in the aforementioned tissues were senescent while the tumour protein 53, a tumour suppressor, was acting to prevent this from happening by activating p21.

"Earlier we discovered that senescent cells accumulate in tissues with ageing and that removal of these cells delays age-related functional decline in these tissues. The key advance of the current study is that the progenitor cell populations are most sensitive for senescence, thereby interfering with the innate capacity of the tissue to counteract degeneration." said Jan van Deursen, senior author of the study.

The study's findings contribute to our current knowledge on cell senescence and how it's related to ageing and related diseases, say the researchers.

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Reference
Baker, D., Weaver, R., & van Deursen, J. (2013). p21 Both Attenuates and Drives Senescence and Aging in BubR1 Progeroid Mice Cell Reports DOI: 10.1016/j.celrep.2013.03.028

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