Modelling human ageing : role of telomeres in stress-induced premature senescence and design of anti-ageing strategies

Due to the duration of human ageing, researchers must rely on models such as animals and cells. Replicative senescence and stress-induced premature senescence (SIPS) are two cellular models sharing many features. Although telomeres play a major role in replicative senescence, their involvement in SIPS is unclear. In this work, we first wanted to investigate how accurate models of ageing are. We published a new model of the evolution of human ageing, which offers a refined view of the evolution of ageing in humans and suggests that human models should be favoured. Though studying other mammals, reptiles, and birds may also be useful, we conclude that lower life forms such as yeast and invertebrates are not representative of the human ageing process. Secondly, we wanted to elucidate the importance of telomeres in SIPS and study gene expression and regulatory networks. Using a telomerase-immortalized cell line, we found no evidence that damage specific to the telomeres is at the origin of SIPS. In our published model, neither the TGF-â1 pathway nor telomeres appear to play a crucial role in SIPS. We suggest that widespread damage to the DNA causes SIPS and propose a rearrangement of gene expression networks as a result of stress. Moreover, we advise caution in using telomerase in anti-ageing therapies since telomerase expression may alter the normal cellular functions and promote tumorogenesis. Lastly, we published strategies to integrate the modern computational approaches to research ageing. Although we find it unlikely that a full understanding of ageing may be achieved within a near future, we argue that understanding the structure and finding key regulatory genes of the human ageing process is possible.