Abstract
Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.
Highlights
Ageing is not a simple passive degenerative process, but one regulated by distinct biochemical pathways
telomerase reverse transcriptase (TERT) can act as a transcription factor (TF) and affect genes involved in energy metabolism, ‘stemness’, and proliferation, including the up-regulation of transfer RNA transcription, interaction with NF-κB and β-catenin to activate their respective pathways, and regulation of cyclin D1 expression [70]
The increased cortisol activity may cause further Mg2+ loss and aggravate the circadian disruption [152]. These findings indicate that the circadian regulation of telomerase activity and Mg2+ homeostasis may play an important role in health, disease, and ageing [144,147]
Summary
Ageing is not a simple passive degenerative process, but one regulated by distinct biochemical pathways. It has been classified by a number of common hallmarks that are shared across taxa. 90% of human cancers demonstrate up-regulation of telomerase activity [7], while most of the remaining 10% use an alternative lengthening of telomeres (ALT) mechanism [8]. This ability to preserve telomere function is necessary to confer replicative immortality, one of the hallmarks of cancer [9]. Factors that mitigate the effect of cellular stress, such as free radical scavengers and antioxidants, may thereby offer the possibility of slowing the rate of telomere attrition [11]
Sign-in/Register to view highlights & summary 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.
