Telomerase gene therapy: a novel approach to combat aging

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Telomeres are repetitive DNA sequences located at the very ends of our chromosomes. Together with specific proteins, they form a cap like structure that prevents the cells from sensing the linear chromosome ends as ‘damaged’. Like a burning fuse, telomeres progressively shorten with every cell division and, depending on cell type, initiate either apoptosis or trigger a permanent proliferative arrest, termed cellular senescence, once a critical length is reached. It is thought that this cell division countdown timer developed as a tumour suppressing mechanism to prevent precancerous cells from proliferating indefinitely. While we currently do not know how efficient this tumour suppressing mechanism is in humans, numerous studies using mouse models have demonstrated that critically short and dysfunctional telomeres indeed present a powerful barrier to cancer growth (Artandi & DePinho, 2010). Unfortunately, this tumour suppressing mechanism also comes at a cost. As we age, telomeres in most of our tissues progressively become shorter and therefore likely contribute to the failure of our organs and tissues observed in old age. Supporting this are data demonstrating that healthy lifespan is positively correlated with longer telomeres in humans, and patients suffering from age‐related diseases and premature aging syndromes display shorter telomeres compared to healthy individuals (Zhu et al, 2011). Furthermore, cells with damaged telomeres accumulate in some tissues of aging mice and nonhuman primates, supporting the model that telomere shortening and the resulting senescence response promotes aging in mammals (Fumagalli et al, 2012; Herbig et al, 2006; Hewitt et al, 2012). Indeed, preventing the accumulation of senescent cells in aging mice significantly improves healthspan, demonstrating that cellular senescence, regardless of its induction, is a cause of aging associated disorders (Baker et al, 2011). Certain cells within our tissues have the ability to stabilize telomere lengths more efficiently than others. …