The molecular basis of ageing in stem cells

Ageing is often defined in the context of telomerase activity and telomere length regulation. Most somatic cells have limited replication ability and undergo senescence eventually. Stem cells are unique as they possess more abundant telomerase activity and are able to maintain telomere lengths for a longer period. Embryonic stem cells are particularly resistant to ageing and can be propagated indefinitely. Remarkably, adult somatic cells can be reprogrammed to an ESC-like state by various means including cell fusion, exposure to ESC cell-free extracts, enforced expression of specific molecules, and somatic cell nuclear transfer. Thus, the rejuvenation of an 'aged' state can be effected by the activation of specific key molecules in the cell. Here, we argue that cellular ageing is a reversible process, and this is determined by the balance of biological molecules which directly or indirectly control telomere length and telomerase activity, either through altering gene expression and/or modulating the epigenetic state of the chromatin.