By Dr. Priyom Bose, Ph.D.Feb 13 2024
Reviewed by Benedette Cuffari, M.Sc.
Aging is associated with many biological, physiological, and psychological changes, some of which include a decline in cognitive function, greying of hair, frailty, and increased risk of contracting certain diseases. Aging also increases the risk of chronic diseases such as diabetes, hypertension, and cardiovascular events.
Most older adults experience chronic magnesium deficiency or hypomagnesemia, which may be due to low dietary magnesium content, reduced intestinal absorption, and increased urination. In a recent review published in the journal Nutrients, researchers discuss the role of magnesium in aging.
Study: Magnesium and the Hallmarks of Aging. Image Credit: monticello / Shutterstock.comStudy: Magnesium and the Hallmarks of Aging. Image Credit: monticello / Shutterstock.com
The role of magnesium in telomere attrition
Telomeres are present at both ends of chromosomes, thereby protecting them from degradation and fusion with other chromosomes to preserve genetic information. Between 50-100 base pairs of telomeric DNA are lost after each cell division; therefore, telomeres shorten as age advances.
When a telomere attains a critical short length, cells recognize it, and replication is attenuated, which results in cell senescence. Previous studies have indicated that magnesium maintains telomeric chromatin structure and integrity, as well as supports telomerase regulation.
Genomic instability
Genomic instability, which involves DNA damage, chromosomal abnormalities, and mutations, is a key driver of aging. Genomic instability occurs due to oxidative stress, epigenetic alterations, inadequate DNA repair, and telomere maintenance.
Throughout the cell cycle, magnesium is essential for stabilizing chromatin assembly. Furthermore, DNA grooves have specific binding sites for magnesium, thereby demonstrating its role in DNA conformation.
Insufficient magnesium levels cause DNA instability through oxidation stress, as various enzymes involved in DNA repair are activated by magnesium. Thus, magnesium plays a crucial role in the DNA replication process and preservation of genome stability.
Epigenetic alterations
Epigenetic alterations refer to the modification of genomic expression without alterations in DNA sequence. The epigenome can be altered through lifestyle factors, diets, and pharmaceutics. Additionally, the age-related inflammatory environment and inhibitory molecules released from stressed cells may lead to epigenetic alterations, which can modify cellular function.
Several studies have highlighted the association of magnesium with epigenetics. For example, hypomagnesemia causes down-regulation of hepatic 11β-hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters, which affect the metabolism of neonatal offspring.
Loss of proteostasis
Proteostasis alterations are associated with weak protein stability and misfolded proteins. Several age-related chronic diseases, such as Alzheimer’s and Parkinson’s disease, have been attributed to the dysregulation of proteostasis. Importantly, low magnesium levels in the brain may lead to many neurological disorders, including epilepsy, Alzheimer’s disease, Parkinson’s disease, and migraines.
Magnesium downregulates tumor-necrosis factor α (TNF-α) and interleukin 1β (IL-1β) production, in addition to supporting the clearance of amyloid β (Aβ) precursor molecules by proteasomal degradation pathways. Magnesium also inhibits the N-methyl-D-aspartate (NMDA) receptor and increases excitatory neurotransmission.
Mitochondrial dysfunction
The mitochondria is involved in multiple cell signaling processes that determine cell fate, including cellular survival and death by apoptosis. Dysfunctional mitochondria can lead to the persistent reduction in cellular adenosine triphosphate (ATP) levels for prolonged periods, which may lead to chronic inflammation, cellular damage, and oxidative stress. These conditions are also linked with age-associated diseases, such as Alzheimer’s disease and Parkinson’s disease.
Magnesium binds with ATP to form the Mg-ATP complex. The presence of intracellular free magnesium has been associated with the development of hypertension and diabetes, both of which are conditions that are more prevalent in older adults. Low magnesium levels are also associated with oxidative stress damage through reduced lipid peroxidation and antioxidant enzyme activity.
Cellular senescence
Cellular senescence is associated with cellular stress and irreversible DNA damage. Additional features of aging include senescence-associated mitochondrial dysfunction, altered nutrient and stress signaling, and autophagy/mitophagy dysfunction.
Certain cellular alterations that occur during senescence are similar to those caused by hypomagnesemia, including reduced protection against oxidative stress damage, cellular viability, cell cycle progression, and enhanced risk of transcription factor expression.
Stem cell exhaustion
Human tissues are maintained by stem cells due to their self-renewing capacity. More specifically, stem cells can differentiate into progenitor cells, from which various tissues are developed.
Previous studies have shown that a reduction in the hemopoietic cells’ regenerative potential due to aging is associated with the reduced production of adaptive immune cells, which is otherwise known as immunosenescence.
Magnesium is strongly linked with immune responses. For example, magnesium is a cofactor for the production of immunoglobulins (Ig), antibody-dependent cytolysis, macrophage response to lymphokines, and immune cell adherence.
Conclusions
Since the aging trajectory is variable, it can be modulated through magnesium intake and lifestyle changes. The current review discusses the importance of suitable magnesium levels throughout life, which may contribute to healthy aging.
Journal reference:
Dominguez, L. J., Veronese, N., & Barbagallo, M. (2024). Magnesium and the Hallmarks of Aging. Nutrients 16(4); 496. doi:10.3390/nu16040496
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