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Melatonin’s Newly Discovered Anti-Aging Mechanism

August 2017

By Scott Franklin

Loss of mitochondrial function contributes to aging throughout the body. Mitochondrial decline opens the door to age-related diseases such as neurodegeneration, diabetes, and obesity.1-12

In a discovery published in 2017, scientists found that the natural hormone melatonin works in a unique way to combat mitochondrial dysfunction.13

A contributor to mitochondrial dysfunction is the opening of a hole in the mitochondrial inner membrane that decreases their ability to produce energy. Preventing or closing this hole is a key to preserving youthful mitochondrial function. Up until recently, there were no drugs able to do so permanently.

This landmark 2017 study reveals that melatonin helps maintain normal levels of an enzyme whose job is to plug that hole.13

By preserving mitochondrial function, melatonin exerts a highly targeted and specific action on a fundamental cause of aging.

Mitochondria and Aging

Mitochondria and Aging  

Melatonin has long been hailed for its benefits on cellular function and disease prevention, as well as its impressive impact on longevity in animal models of aging.14-21

In a study published in 2017, scientists uncovered a new way that melatonin promotes longevity. This new mechanism involves melatonin’s ability to preserve mitochondrial function.

To fully grasp the impact of the study’s findings, we first need to review some background information.

Mitochondrial dysfunction plays a large role in aging and disease because mitochondria are the powerhouses of our cells. By “burning” fuel supplied by the food we eat, mitochondria release massive amounts of energy needed to power the human body.

This energy release occurs in the form of molecules of ATP (adenosine triphosphate). ATP drives every cellular function that requires energy. Low levels of ATP result in diminished energy, decreased cellular function, and, eventually, poor tissue, organ, and system function throughout the body.

The number of mitochondria in our cells, and their efficient function, degrades over time. This accounts for a large part of the aging we experience in the form of increased disease vulnerability and shortened lifespans.1-3

Mitochondrial Death Channel

A contributor to mitochondrial dysfunction is the activation of a protein in the mitochondrial inner membrane called MPTP, or mitochondrial permeability transition pore.22-24 The MPTP forms a channel, or pore, through the mitochondrial membrane25,26

MPTP opening is not good because it causes swelling, as water and small chemical molecules flow nonstop into the mitochondria.13 This is followed by a sudden sharp loss of the mitochondria’s ability to retain their essential electric charge. The result is a collapse of energy production, a decrease in ATP supplies, and increased oxidative stress on cells.24

Numerous studies show that opening of the MPTP is associated with common diseases of aging, and with markers of aging itself in human tissues.25-31 Closing the MPTP is essential for long-lived, efficient mitochondria.13,24,28

The new study shows us for the first time that melatonin supplementation can dramatically reduce the MPTP opening, thereby reducing the impact of dead and dying mitochondria on aging without resorting to toxic and expensive drugs.

New Findings

In the study published in early 2017, researchers in South Carolina and Russia teamed up to investigate details of how melatonin interacts with the MPTP to boost and preserve mitochondrial function.13 In an entirely new development, the researchers found that melatonin improved mitochondrial function by boosting levels of an enzyme involved in controlling MPTP holes.13

The enzyme, called CNPase, protects mitochondria. It does this by breaking down a molecule that promotes the opening of the MPTP. Continued CNPase activity is necessary for maintaining normal mitochondrial function and energy availability in the cell.13

But animal research has shown that CNPase levels fall by as much as 34% with aging, accompanied with loss of mitochondrial electrical function by up to 69%.24 This has dangerous effects on overall tissue and organ function.

The new study found that melatonin helps maintain normal levels of CNPase within mitochondria, where it suppresses MPTP. This maintains normal electrical function in mitochondria and contributes to normal tissue and organ function, resistance to disease, and slower aging.13

These findings indicate that, at the most basic possible level, melatonin contributes to disease resistance and age deceleration through its direct impact on mitochondrial function.

Melatonin and Aging
Melatonin and Aging

Loss of mitochondrial function is a known fundamental contributor to aging throughout the body, predisposing us to age-related diseases such as coronary artery disease, neurodegeneration, and metabolic disturbances like diabetes and obesity.

A major contributor to mitochondrial dysfunction is the opening of a hole in mitochondrial membranes that results in swelling and eventual death of individual mitochondria.

Studies reveal that melatonin preserves healthy mitochondrial function by safely and effectively preventing the opening of the pore.

Life Extension® recommends regular melatonin supplementation to prevent mitochondrial degradation, and to preserve youthful energy supplies.

Melatonin is a low-cost supplement that has been available to Americans since 1992.

Melatonin as Mitochondrial Medicine

The findings of this new study lend additional weight to the evidence that melatonin prevents age-associated disease through its impact on mitochondrial health.19

This should not be surprising, considering the highest concentrations of melatonin inside of cells is found in the mitochondria, which suggests an important natural role for its effects on energy production and cellular integrity.32

Indeed, melatonin is known for its ability to extend the lifespan of multiple species, from insects to mammals. This effect is accomplished through melatonin’s ability to protect mitochondria, promote longevity-associated proteins such as SIRT1, and reduce oxidative stress that can induce mitochondrial destruction.14-21

Specifically, melatonin can:

  • Prevent age-related mitochondrial dysfunction in brain cells, with the potential to slow or prevent neurodegenerative diseases,4,8-10
  • Prevent death of skeletal muscle cells through supporting mitochondrial energy production,5
  • Protect heart muscle cells following loss of blood flow (ischemia) during and after a heart attack,6
  • Improve mitochondrial function, and hence, energy utilization, in fat tissues of animal models of diabetes and obesity,11
  • Alleviate fatty liver disease by protecting liver mitochondria in similar animal models,12
  • Improve function of smooth muscle cells in intestines, which often slows down during aging as their energy supplies are threatened.2

With its newly-discovered ability to support the CNPase enzyme, and the resulting prevention of MPTP formation, melatonin helps preserve youthful function in every tissue in the body.

And since most human cells and tissues contain mitochondria, that translates to a vital protective effect of melatonin in all body organs and systems.

Summary

Loss of mitochondrial function is a fundamental contributor to aging in every cell, tissue, organ, and body system in humans.

A landmark study published in early 2017 has shown that melatonin supplementation supports youthful mitochondrial function by preventing the expression of an opening, or pore, or “hole” in mitochondrial membranes that would otherwise degrade their ability to generate energy.

This results in enhanced mitochondrial function, and a reduction in age-related diseases—and it goes a long way to explaining melatonin’s known longevity-promoting properties.

By supplementing with melatonin, we can preserve youthful energy supplies by providing protection for the body’s main energy source.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Ganie SA, Dar TA, Bhat AH, et al. Melatonin: A Potential Anti-Oxidant Therapeutic Agent for Mitochondrial Dysfunctions and Related Disorders. Rejuvenation Res. 2016;19(1):21-40.
  2. Martin-Cano FE, Camello-Almaraz C, Acuna-Castroviejo D, et al. Age-related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin. J Pineal Res. 2014;56(2):163-74.
  3. Paradies G, Paradies V, Ruggiero FM, et al. Protective role of melatonin in mitochondrial dysfunction and related disorders. Arch Toxicol. 2015;89(6):923-39.
  4. Petrosillo G, Fattoretti P, Matera M, et al. Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection. Rejuvenation Res. 2008;11(5):935-43.
  5. Hibaoui Y, Roulet E, Ruegg UT. Melatonin prevents oxidative stress-mediated mitochondrial permeability transition and death in skeletal muscle cells. J Pineal Res. 2009;47(3):238-52.
  6. Petrosillo G, Colantuono G, Moro N, t al. Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening. Am J Physiol Heart Circ Physiol. 2009;297(4):H1487-93.
  7. Petrosillo G, Moro N, Ruggiero FM, et al. Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release. Free Radic Biol Med. 2009;47(7):969-74.
  8. Jou MJ. Melatonin preserves the transient mitochondrial permeability transition for protection during mitochondrial Ca(2+) stress in astrocyte. J Pineal Res. 2011;50(4):427-35.
  9. Ozturk G, Akbulut KG, Guney S, et al. Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: modulation by melatonin. Exp Gerontol. 2012;47(9):706-11.
  10. Cardinali DP, Pagano ES, Scacchi Bernasconi PA, et al. Melatonin and mitochondrial dysfunction in the central nervous system. Horm Behav. 2013;63(2):322-30.
  11. Jimenez-Aranda A, Fernandez-Vazquez G, Mohammad ASM, et al. Melatonin improves mitochondrial function in inguinal white adipose tissue of Zucker diabetic fatty rats. J Pineal Res. 2014;57(1):103-9.
  12. Agil A, El-Hammadi M, Jimenez-Aranda A, et al. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats. J Pineal Res. 2015;59(1):70-9.
  13. Baburina Y, Odinokova I, Azarashvili T, et al. 2’,3’-Cyclic nucleotide 3’-phosphodiesterase as a messenger of protection of the mitochondrial function during melatonin treatment in aging. Biochim Biophys Acta. 2017;1859(1):94-103.
  14. Stacchiotti A, Favero G, Lavazza A, et al. Hepatic Macrosteatosis Is Partially Converted to Microsteatosis by Melatonin Supplementation in ob/ob Mice Non-Alcoholic Fatty Liver Disease. PLoS One. 2016;11(1):e0148115.
  15. Jenwitheesuk A, Nopparat C, Mukda S, et al. Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways. Int J Mol Sci. 2014;15(9):16848-84.
  16. Teran R, Bonilla E, Medina-Leendertz S, et al. The life span of Drosophila melanogaster is affected by melatonin and thioctic acid. Invest Clin. 2012;53(3): 250-61.
  17. Chang HM, Wu UI, Lan CT. Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats. J Pineal Res. 2009;47(3):211-20.
  18. Rodriguez MI, Escames G, Lopez LC, et al. Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice. Exp Gerontol. 2008;43(8):749-56.
  19. Anisimov VN, Popovich IG, Zabezhinski MA, et al. Melatonin as antioxidant, geroprotector and anticarcinogen. Biochim Biophys Acta. 2006;1757(5-6): 573-89.
  20. Hevia D, Gonzalez-Menendez P, Quiros-Gonzalez I, et al. Melatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer. J Pineal Res. 2015;58(2):234-50.
  21. Magnanou E, Attia J, Fons R, et al. The timing of the shrew: continuous melatonin treatment maintains youthful rhythmic activity in aging Crocidura russula. PLoS One. 2009;4(6):e5904.
  22. Jackson EK, Menshikova EV, Mi Z, et al. Renal 2’,3’-Cyclic Nucleotide 3’-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion. J Am Soc Nephrol. 2016;27(7):2069-81.
  23. Baburina Y, Azarashvili T, Grachev D, et al. Mitochondrial 2’, 3’-cyclic nucleotide 3’-phosphodiesterase (CNP) interacts with mPTP modulators and functional complexes (I-V) coupled with release of apoptotic factors. Neurochem Int. 2015;90:46-55.
  24. Krestinina O, Azarashvili T, Baburina Y, et al. In aging, the vulnerability of rat brain mitochondria is enhanced due to reduced level of 2’,3’-cyclic nucleotide-3’-phosphodiesterase (CNP) and subsequently increased permeability transition in brain mitochondria in old animals. Neurochem Int. 2015;80:41-50.
  25. Ichas F, Mazat JP. From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim Biophys Acta. 1998;1366(1-2):33-50.
  26. Lemasters JJ, Nieminen AL, Qian T, et al. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta. 1998;1366(1-2):177-96.
  27. Baines CP. The cardiac mitochondrion: nexus of stress. Annu Rev Physiol. 2010;72:61-80.
  28. Bopassa JC, Michel P, Gateau-Roesch O, et al. Low-pressure reperfusion alters mitochondrial permeability transition. Am J Physiol Heart Circ Physiol. 2005;288(6):H2750-5.
  29. Fiskum G. Mitochondrial participation in ischemic and traumatic neural cell death. J Neurotrauma. 2000;17(10): 843-55.
  30. Honda HM, Ping P. Mitochondrial permeability transition in cardiac cell injury and death. Cardiovasc Drugs Ther. 2006;20(6):425-32.
  31. Schinder AF, Olson EC, Spitzer NC, et al. Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J Neurosci. 1996;16(19):6125-33.
  32. Paradies G, Petrosillo G, Paradies V, et al. Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease.J Pineal Res. 2010;48(4): 97-310.