[HTML][HTML] Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing

F Rossiello, U Herbig, MP Longhese… - Current opinion in …, 2014 - Elsevier
F Rossiello, U Herbig, MP Longhese, M Fumagalli, FA di Fagagna
Current opinion in genetics & development, 2014Elsevier
The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage
is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular
senescence. Organismal ageing in mammals is associated with accumulation of markers of
cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells
in mammals are non-proliferating, how do they age? Are telomeres involved? Also
oncogene activation causes cellular senescence due to altered DNA replication and DDR …
The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?
Elsevier