April 2, 2015

Aging insights from budding yeast

The proteins that control entry and exit from the cell nucleus influence aging, Vanderbilt researchers have discovered.

Nuclear pore complexes (NPCs) – structures composed of about 30 nucleoporin (Nup) proteins – regulate transport between the nucleus and cytoplasm. Multiple studies have noted correlations between cell longevity, NPCs and nuclear transport, but there is no direct evidence that alterations in NPC function cause changes in cellular life span.

Susan Wente, Ph.D., and colleagues used the replicative life span (RLS) of Saccharomyces cerevisiae (the number of daughter yeast cells that bud from a mother cell before senescence or death) as a model to test whether NPCs directly affect longevity. The investigators report in the March 16 Journal of Cell Biology that specific Nups and transport events regulate longevity independent of changes in NPC permeability. For example, they demonstrated that mutant cells lacking a certain domain of Nup116 have decreased RLSs, while longevity increased in mutants missing Nup100.

The studies reveal that specific NPC nuclear transport events directly influence aging, and could lead to new insights for preventing aging-related disease processes.

This research was supported by grants from the National Institutes of Health (CA009582, AG047737, GM051219).

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