ABSTRACT
There are several observations that are difficult to explain using classical Mendelian inheritance. These include position effect variegation, transvection, telomere position effect and imprinting. These phenomena are now known to be based on changes in chromatin structure and epigenetic modifications that can be transmitted to daughter cells. It is, therefore, possible that abnormal chromatin packaging can lead to abnormal cellular processes that ultimately disturb the cell’s sustenance. For example, de-repression of telomeric heterochromatin can lead to cellular senescence (Kennedy et al. 1997; Moazed 2001). This indicates that during aging the ability to compensate for cellular damage fails to meet the need for repair or replenishment of the maintenance factors (Steinkraus et al. 2008). Non-dividing cells maintain their pool to repair internal damage by optimizing the supply of chromatin components. Actively dividing cells need massive synthesis of such components. Eukaryotic cells cannot undergo cell division indefinitely and, therefore, have an inherent lifespan, called the replicative lifespan. After a certain number of replications, the mother cell accumulates aging-related damage, which ultimately causes it to cease further divisions. In multicellular organisms, each tissue has a characteristic replicative capacity (Cavalier-Smith 1978). Much of the information about aging has come from the yeast Saccharomyces cerevisiae (Steinkraus et al. 2008). Several key factors affecting aging are conserved from yeast to worms to mammals (Kaeberlein et al. 1999; Wood et al. 2004; Kenyon 2010). These include calorie restriction, radical oxygen species (ROS)-dependent signal transduction, sirtuin-mediated anti-aging functions and the target of rapamycin (TOR) pathway. Budding yeasts try to prevent the passing of cellular components with aging-related damage such as damaged proteins, or extra-chromosomal DNA fragments, to the daughter cells during cell division (Kaeberlein et al. 1999). As a cell undergoes many divisions, it becomes increasingly difficult for the cell to prevent passage of this load to the daughter cells. So the accumulation of damaged components can itself act as a trigger for replicative senescence (Steinkraus et al. 2008). Consequently, factors that reduce this load assume the role of safeguarding against the aging process. Many of the factors that prevent aging can alter gene expression via chromatin modifications. Therefore, chromatin modifiers such as Sir2, the Polycomb group (PcG) of proteins (Jacobs et al. 1999), histone deacetylases and histone chaperones (Chen et al. 2008; Dang et al. 2009) are being related to aging processes. Can key structural components of chromatin such as the histone proteins be directly involved in replicative aging? A recent report demonstrates a direct connection between the levels of histones and the lifespan of budding yeast (Feser et al. 2010). It was shown that aging cells have low histone protein levels, resulting in loose packaging of the genome and hence inappropriate gene regulation.