Date Published: November 10, 2011
Publisher: Impact Journals LLC
Author(s): Olga V. Leontieva, Mikhail V. Blagosklonny.
In yeast, chronological senescence (CS) is defined as loss of viability in stationary culture. Although its relevance to the organismal aging remained unclear, yeast CS was one of the most fruitful models in aging research. Here we described a mammalian replica of yeast CS: loss of viability of overgrown “yellow” cancer cell culture. In a density and time (chronological)-dependent manner, cell culture loses the ability to re-grow in fresh medium. Rapamycin dramatically decelerated CS. Loss of viability was caused by acidification of the medium by lactic acid (lactate). Rapamycin decreased production of lactate, making conditioned medium (CM) less deadly. Both deadly CM and lactate caused loss of viability in low cell density, not preventable by either rapamycin or additional glucose. Also, NAC, LY294002, U0126, GSK733, which all indirectly inhibit mTOR and have been shown to suppress the senescent phenotype in traditional models of mammalian cell senescence, also decreased lactate production and decelerated CS. We discuss that although CS does not mimic organismal aging, the same signal transduction pathways that drive CS also drive aging.
In yeast, chronological senescence (CS) is defined as loss of viability of yeast cells grown in confluent state [1-10]. Viability is determined as the ability to resume replication in fresh medium. CS is genetically regulated and inactivation of numerous genes including TOR (Target of Rapamycin) extends lifespan [2, 11-23]. Furthermore, rapamycin, an inhibitor of TOR, decelerates CS in yeast . Noteworthy, the TOR (target of rapamycin) pathway is involved in aging of variety of species from worm to mammals [25-28]. Some other genes identified in the yeast model turned out to be involved in organismal aging and age-related diseases in mammals [29-38]. CS is often compared to aging of postmitotic cells in the organism. However, as recently discussed, the link between CS and organismal aging is not immediately apparent but indirectly relies on common genetic pathways .
Here we described a mammalian model of yeast-like chronological senescence (CS). Regardless of how trivial this phenomenon is, it is the replica of yeast CS.