Abstract
The replicative limit of human fibroblasts has long provided a model to assess the molecular mechanisms which underlie cellular aging. In culture, fibroblasts which reach the end of their proliferative lifespan acquire profound molecular changes that limit their response to growth factors, and cause permanent exit from the cell cycle. Part of the senescence programme is due to a well established link between telomere attrition which occurs with each population doubling and the subsequent activation of the p53 tumour suppressor. Critical shortening of telomeres is thought to cause a form of DNA damage, that leads to the activation of caretaker proteins ATM, ATR or DNA-PK which activate p53, leading to the initiation of senescence through p53 effector genes. In addition, p53 mediates senescence by many other stimuli including oxidative stress, DNA damaging agents and oncogenic activation.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
