Decaying Cellular Waste Disposal Pumps Linked to Cellular Aging
The maternal instincts of yeast cells to protect their offspring from the damaging effects of cellular toxic waste appears to promote their own demise, but this altruistic act also provides new insights in cellular aging and importantly age-related diseases such as cancer.
Most cells appear to have a finite ability to replicate, after which they enter a stage of cell aging, also known as cellular senescence during which toxic agents build up within cells. Research reported by Li et al. this week in Nature Cell Biology provides further ideas on how and why this occurs.
Li et al., used bakers’ yeast, Saccharomyces cerevisiae, as a model to for studying aging, in which cells divide asymmetrically producing a ‘mother’ and ‘daughter’ cell which are not identical. Previous studies have shown that during yeast cell division, the mother keeps the damaged proteins which are toxic and could be harmful to the daughter cell. Dr Li and her team discovered that the mother yeast cell keeps an old set of a specific type of protein called a Multi Drug Resistant (MDR) protein, but gives the daughter cells a completely new set. MDR proteins are well known already, as they have been implicated in resistance to some cancer drugs, by expelling the drug from the cell. However, they also transport compounds in and out of normal cells.
Li et al., found that these MDR proteins decayed and lost their function right at the end of the cells’ life, suggesting that they are limiting the lifespan of cells effectively resulting in the loss of a cell’s fitness. As a result, Li et al., hypothesized that if the loss of MDR proteins contributes to aging, then cells lacking MDR proteins should have a reduced lifespan (measured by the replicative ability of the mother cell), and that is exactly what happened- losing one MDR gene and the resultant lack of a particular MDR protein reduced the replicative ability of the mother cell by up to 66%. Conversely, when extra copies of MDR genes were inserted in the mother yeast cell, which led to over expression of MDR genes, the investigators saw an increase in replicative ability.
How this translates into humans, is not yet clear but the MDR proteins are conserved across organisms suggesting that they may have an important role in aging. This process mayalso explain why cancer cells which contain high levels of MDRs are immortal.