Telomere Homeostasis: Interplay with Magnesium

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.

Keywords: TERT; magnesium; mitochondria; oxidative stress; telomerase; telomeres.

Figure 1

Schematic representation of an antiparallel G-quadruplex formed from a single DNA strand. This type of structure can form at telomere ends, protecting and stabilising the single strand overhang. The G-quadruplex is composed of several stacked G-tetrads, each of which is in turn formed by four guanines (G) joined by Hoogsteen hydrogen bonding and stabilised by a monovalent cation (K⁺ in this figure).

Figure 2

A schematic of the interplay between mitochondria, telomere nucleo-protein complexes and proteo-biosynthesis regulation in response to cellular stress/damage. In response to the stress, the cell will decide how much fuel to burn and energy to expend to repair any damage accrued. If the cell can repair the damage it can progress through the cell cycle. Too much damage and the high risk of onconeogenesis induces cell death. Senescence, strictly in this simplified scenario, sees the cell carry accumulated, sub-lethal damage, as wear and tear, leaving the cell metabolically active, but physiologically non-contributory to the function of the tissue and organ in which it resides. The pervasive and overlapping roles that TERT (green) and magnesium (orange) play in targeting major components of the MRT trinity are highlighted. ER, mTOR/.