Investigating the link between chronological and replicative aging

By: Chris Murakamai

In a paper published in 1999, Ashrafi et al. showed that yeast cells maintained in stationary phase for a prolonged period of time displayed a reduced replicative life span. This reduction in life span was not due to permanent genetic damage however, since daughters and granddaughters of chronologically-aged mother cells showed no reduction in mean replicative life span and lived to the same extent that non-aged cells did. Our lab has previously shown that much of the reduction of chronological life span in synthetic medium can be attributed to a reduction in culture pH, more specifically the production of acetic acid during fermentative growth.  This shortening of life span can be rescued by growth and subsequent chronological aging in media that promotes a higher culture pH such as buffering to a pH of 6.0, growth in YEPD, or dietary restriction by reduction in glucose concentration.

Currently we are now studying whether maintaining cells in media types that extend chronological life span will result in an extension in replicative life span as well. To perform these studies, we will age stationary phase cells in standard synthetic medium as well as several media conditions known to extend chronological life span. At set time points, a small aliquot of cells will be removed from the aged cultures and be spotted onto YEPD plates, where single cells will be set up and the number of divisions will be counted.

These studies could provide another important link between the chronological and replicative aging models, two aging paradigms generally thought to be distinct.