Abstract
Rejuvenation of stem cell activity might increase life expectancy by prolonging functionality of organs. Higher stem cell replication rates also bear the risk of cancer. The extent of this risk is not known. While it is difficult to evaluate this cancer risk in experiments, it can be estimated using a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model recapitulates the observation that treatments targeting stem cell replication can induce a substantial delay of organ failure. The model predicts that the cancer risk is minor under particular conditions. It depends on the assumed implications for cell damage repair during treatment. The benefit of rejuvenation therapy and its impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of systemic treatments. In recent years, the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. In this context, the model predicts that the treatment schedule is critical for success and that schedules successful in animal experiments are not transferable to humans. Guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of stem cell rejuvenation treatment protocols and the identification of critical parameters for cancer risk.
Highlights
Biological organisms like humans accumulate DNA damage in replicating cells inducing many processes summarised under the general term of ageing
The model complexity is chosen such that the driving question, whether cancer risk is under control during rejuvenation therapy or not, can be addressed, avoiding speculations on molecular mechanisms
The mathematical analysis of the impact of rejuvenation treatments improving stem cell replication and tissue regeneration predicts that organ failure is delayed at the cost of an increased risk of developing cancer
Summary
Biological organisms like humans accumulate DNA damage in replicating cells inducing many processes summarised under the general term of ageing. Organ failure is more sensitive to constant stem cell replication rates than cancer risk. In order to determine the sensitivity of organ failure and cancer risk to changes in the division rate, the constant stem cell replication rate p is varied.
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