Life Extension Magazine®

Issue: May 2020

How PQQ Slows Aging

A nutrient called PQQ restores youthful cell functions, delays cell senescence, and extends lifespan in animals.

Scientifically reviewed by: Julia Dosik, MPH, on April 2020. Written By Janice Hamilton.

A nutrient called PQQ (pyrroloquinoline quinone) restores youthful cellular function and extends the lifespan of worms.1,2

PQQ helps mitochondria—the “powerhouses” of the cell—work more efficiently.

It also promotes formation of new mitochondria in aging cells. Dysfunctional mitochondria contribute to body-wide degeneration. 2-9

But it turns out PQQ does much more.

A team of researchers from China and Italy found that when PQQ was applied to human cells in culture, it delayed cellular senescence.10

A growing body of research suggests that reducing cellular senescence may lead to increased healthspan and lifespan.

This one-two punch—promoting mitochondrial health and slowing cellular senescence —explains why PQQ has powerful potential to slow aging processes.

In fact, in those recent worm studies, PQQ increased lifespan by roughly 30%.1,2

Stopping Cellular Senescence

Low-level chronic inflammation is a key contributor to aging of the human body.

As we age, levels of inflammation-stoking messenger molecules called cytokines increase, contributing to greater risk of cardiovascular disease, neurodegenerative diseases, diabetes, cancer, and more.

This phenomenon, known as inflammaging, is a major factor in the aging process itself.11,12

In a preclinical cell study, the nutrient PQQ (pyrroloquinoline quinone) showed the ability to block the effects of these harmful molecules by interfering with the signaling pathways they provoke to induce cellular senescence and inflammaging.10

Testing PQQ in Human Cells

Computer image of a heart

A team of scientists recently set out to determine whether PQQ could slow cell aging caused by inflammatory signaling, and reduce the number of senescent cells.10

Researchers first grew human lung cells in a nutrient broth, and added inflammaging-associated proteins, including TNF-alpha, to some of the cell samples.10

TNF-alpha promoted senescence and inflammaging in the treated cells. But when cells were pre-treated with PQQ before the TNF-alpha, the numbers of senescent cells in the culture dropped to significantly less than those in the untreated group.

Other signs of inflammaging were also reduced in PQQ-treated cells.

This study shows that PQQ can inhibit cellular aging by reducing TNF-alpha’s ability to stimulate senescence. This is a promising finding for PQQ’s ability to slow aging throughout the body and help prevent age-related disease.

Protecting the Heart

In energy-consuming cells like those in the heart, PQQ functions almost like a “fuel additive”, helping to burn fuel more efficiently.

In animals suffering heart attacks, insufficient PQQ contributes to worse outcomes.13

Animal studies show that increasing PQQ in models of heart attack can:14-17

  • Shrink the size of the infarct, or damaged area, in the heart muscle,
  • Improve cardiac function following loss of blood flow (ischemia) to the heart muscle,
  • Boost the function of mitochondria in ailing heart cells subjected to ischemia, and
  • Prevent heart muscle death after ischemia.

These benefits are likely attributable to PQQ’s ability to combat oxidative stress and its effects on signaling pathways.17,18

Benefits for Diabetes

Microscope

PQQ was shown in a cell culture study to block oxidative stress and cell death caused by high glucose, through an effect on signaling pathways.19

By battling oxidative stress and modulating insulin signaling pathways, PQQ has been shown in diabetic animals and in lab studies to:19-23

  • Lower blood sugar,
  • Decrease lipid abnormalities,
  • Activate insulin signaling to increase glucose tolerance,
  • Reduce glucose-induced oxidative stress in brain tissue, a contributor to neurodegenerative diseases, and
  • Protect kidney cells against events leading to diabetic kidney disease.

PQQ also increases production of the “longevity protein” Sirt3, a longevity-associated factor that supports healthy mitochondrial function.24,25

Building Stronger Bones

In aging bone, senescent cells accumulate, pouring out damaging pro-inflammatory signaling molecules.26 This is yet another mechanism involved in the destructive effects of inflammaging.

Over time, inflammaging contributes to lower rates of new bone formation and higher rates of bone breakdown. The result: weaker, fracture-prone bones.27

Animal studies have shown that PQQ can promote bone formation and prevent bone degradation. It accomplishes this through multiple, different pathways, including oxidative stress, hormonal, and complex signaling pathways.28-32

In these studies, PQQ’s effects included the ability to:

  • Strengthen and thicken healthy bone,
  • Rescue weakening bone from further breakdown,
  • Inhibit inflammatory secretions from senescent cells,
  • Prevent bone loss related to low levels of estrogen (like that seen in menopause) and testosterone,
  • Stimulate new bone formation,
  • Slow the development of bone-depleting osteoclasts, and
  • Promote formation of bone-producing osteoblasts.
Blood meter

WHAT YOU NEED TO KNOW

Fight Aging with PQQ

  • Damaged, aging cells called senescent cells give off age-promoting signaling molecules.
  • These harmful molecular signals promote inflammation and are a major driver of aging and age-related disease.
  • PQQ (pyrroloquinoline quinone) is a vitamin-like nutrient that is known for its ability to protect the mitochondria and promote the formation of new mitochondria.
  • A new cell-based study shows that PQQ can also reduce senescent cells and block the harmful signals they give off.
  • PQQ may also slow the overall aging process itself, and has been shown to extend lifespan by 30% in animal studies.

Help for the Aging Brain

The brain consumes more energy than any other organ in the body.

That makes brain tissue especially vulnerable to disruptions in its energy supply.

In fact, aging mitochondria are known to contribute to many age-related brain disorders, including Alzheimer’s and Parkinson’s disease.33,34

By helping mitochondria perform more efficiently and by promoting the development of new mitochondria, PQQ may help prevent these diseases.23,35,36

Studies in rats show that increasing PQQ can minimize brain injury induced by rotenone, a neurotoxin that causes Parkinson’s-like symptoms.36 Rats receiving rotenone and then being treated with PQQ suffer less loss of brain cells and perform better on lab tests afterward compared with untreated animals.

PQQ also protects brain cells against excitotoxicity, which is believed to be one cause of Alzheimer’s disease.37 Excitotoxicity occurs when nerve cells are damaged or killed by overactivity of the neurotransmitter glutamate.38

In a cell culture study, PQQ countered glutamate’s destructive effects by stimulating growth of neural stem cells and reducing damage to brain cells.39

Extending Lifespan

When senescent cells accumulate, it accelerates aging processes.12 By reducing the number of senescent cells, PQQ may increase lifespan.

Two different research groups evaluated PQQ’s life-extending effects on a type of roundworm, C. elegans, which is commonly used to study longevity.

The findings were nearly identical. In one study, giving the animals PQQ increased lifespan by an average of 30%. In the other study, the animal models lived an average of 31% longer.1,2

Summary

PQQ (pyrroloquinoline quinone) is a compound that protects mitochondria, the “powerhouses” of our cells.

It promotes the formation of new, healthy mitochondria. This has anti-aging benefits throughout the body.

Recent studies have shown a way that PQQ may be able to slow aging evenmore, by reducing the activity of certain age-accelerating signaling pathways.

This can help lower chronic inflammation and aging-promoting senescent cells.

By slowing cellular aging, PQQ can help lower risks of cardiovascular disease, diabetes, osteoporosis, and neurodegenerative disorders.

Since PQQ has effects on so many aging pathways, it is a prime candidate for targeting the aging process itself and extending healthy lifespan.

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. Sasakura H, Moribe H, Nakano M, et al. Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans. J Cell Sci. 2017 Aug 1;130(15):2631-43.
  2. Wu JZ, Huang JH, Khanabdali R, et al. Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans. Exp Gerontol. 2016 Jul;80:43-50.
  3. Hwang P, Willoughby DS. Mechanisms Behind Pyrroloquinoline Quinone Supplementation on Skeletal Muscle Mitochondrial Biogenesis: Possible Synergistic Effects with Exercise. J Am Coll Nutr. 2018 May 1:1-11.
  4. Lu J, Chen S, Shen M, et al. Mitochondrial regulation by pyrroloquinoline quinone prevents rotenone-induced neurotoxicity in Parkinson’s disease models. Neurosci Lett. 2018 Nov 20;687:104-10.
  5. Martino Adami PV, Quijano C, Magnani N, et al. Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer’s disease. J Cereb Blood Flow Metab. 2017 Jan;37(1):69-84.
  6. Ng CH, Basil AH, Hang L, et al. Genetic or pharmacological activation of the Drosophila PGC-1alpha ortholog spargel rescues the disease phenotypes of genetic models of Parkinson’s disease. Neurobiol Aging. 2017 Jul;55:33-7.
  7. Saihara K, Kamikubo R, Ikemoto K, et al. Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1alpha Signaling Pathway. Biochemistry. 2017 Dec 19;56(50):6615-25.
  8. Singh AK, Pandey SK, Saha G, et al. Pyrroloquinoline quinone (PQQ) producing Escherichia coli Nissle 1917 (EcN) alleviates age associated oxidative stress and hyperlipidemia, and improves mitochondrial function in ageing rats. Exp Gerontol. 2015 Jun;66:1-9.
  9. Zhang J, Meruvu S, Bedi YS, et al. Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells. Nutr Res. 2015 Sep;35(9):844-9.
  10. Hao J, Ni X, Giunta S, et al. Pyrroloquinoline quinone delays inflammaging induced by TNF-alpha through the p16/p21 and Jagged1 signalling pathways. Clin Exp Pharmacol Physiol. 2020 Jan;47(1):102-10.
  11. Available at: https://www.nia.nih.gov/about/living-long-well-21st-century-strategic-directions-research-aging/inflammation-plays. Accessed March 4, 2020.
  12. Rea IM, Gibson DS, McGilligan V, et al. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front Immunol. 2018 2018-April-09;9(586):586.
  13. Bauerly K, Harris C, Chowanadisai W, et al. Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS One. 2011;6(7):e21779.
  14. Zhu BQ, Zhou HZ, Teerlink JR, et al. Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion. Cardiovasc Drugs Ther. 2004 Nov;18(6):421-31.
  15. Zhu BQ, Simonis U, Cecchini G, et al. Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury. J Cardiovasc Pharmacol Ther. 2006 Jun;11(2):119-28.
  16. Tao R, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007 Nov 16;363(2):257-62.
  17. Xu F, Yu H, Liu J, et al. Pyrroloquinoline quinone inhibits oxygen/glucose deprivation-induced apoptosis by activating the PI3K/AKT pathway in cardiomyocytes. Mol Cell Biochem. 2014 Jan;386(1-2):107-15.
  18. Ames BN. Prolonging healthy aging: Longevity vitamins and proteins. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10836-44.
  19. Wang Z, Li Y, Wang Y, et al. Pyrroloquinoline quinine protects HK-2cells against high glucose-induced oxidative stress and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathway. Biochem Biophys Res Commun. 2019 Jan 8;508(2):398-404.
  20. Takada M, Sumi M, Maeda A, et al. Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-A(y) mice. Biochem Biophys Res Commun. 2012 Nov 16;428(2):315-20.
  21. Kumar N, Kar A. Pyrroloquinoline quinone (PQQ) has potential to ameliorate streptozotocin-induced diabetes mellitus and oxidative stress in mice: A histopathological and biochemical study. Chem Biol Interact. 2015 Oct 5;240:278-90.
  22. Kumar N, Kar A. Pyrroloquinoline quinone ameliorates oxidative stress and lipid peroxidation in the brain of streptozotocin-induced diabetic mice. Can J Physiol Pharmacol. 2015 Jan;93(1):71-9.
  23. Wang Z, Chen GQ, Yu GP, et al. Pyrroloquinoline quinone protects mouse brain endothelial cells from high glucose-induced damage in vitro. Acta Pharmacol Sin. 2014 Nov;35(11):1402-10.
  24. Gomes P, Viana SD, Nunes S, et al. The yin and yang faces of the mitochondrial deacetylase sirtuin 3 in age-related disorders. Ageing Res Rev. 2020 Jan;57:100983.
  25. Benigni A, Perico L, Macconi D. Mitochondrial Dynamics Is Linked to Longevity and Protects from End-Organ Injury: The Emerging Role of Sirtuin 3. Antioxid Redox Signal. 2016 Aug 1;25(4):185-99.
  26. Pignolo RJ, Samsonraj RM, Law SF, et al. Targeting Cell Senescence for the Treatment of Age-Related Bone Loss. Curr Osteoporos Rep. 2019 Apr;17(2):70-85.
  27. Khosla S, Farr JN, Kirkland JL. Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1282-90.
  28. Geng Q, Gao H, Yang R, et al. Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence. Int J Biol Sci. 2019;15(1):58-68.
  29. Wu X, Li J, Zhang H, et al. Pyrroloquinoline quinone prevents testosterone deficiency-induced osteoporosis by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. Am J Transl Res. 2017;9(3):1230-42.
  30. Kong L, Yang C, Yu L, et al. Pyrroloquinoline quinine inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos in mouse bone marrow cells and inhibits wear particle-induced osteolysis in mice. PLoS One. 2013;8(4):e61013.
  31. Huang Y, Chen N, Miao D. Pyrroloquinoline quinone plays an important role in rescuing Bmi-1(-/-) mice induced developmental disorders of teeth and mandible--anti-oxidant effect of pyrroloquinoline quinone. Am J Transl Res. 2018;10(1):40-53.
  32. Huang Y, Chen N, Miao D. Effect and mechanism of pyrroloquinoline quinone on anti-osteoporosis in Bmi-1 knockout mice-Anti-oxidant effect of pyrroloquinoline quinone. Am J Transl Res. 2017;9(10):4361-74.
  33. Blanch M, Mosquera JL, Ansoleaga B, et al. Altered Mitochondrial DNA Methylation Pattern in Alzheimer Disease-Related Pathology and in Parkinson Disease. Am J Pathol. 2016 Feb;186(2):385-97.
  34. Macdonald R, Barnes K, Hastings C, et al. Mitochondrial abnormalities in Parkinson’s disease and Alzheimer’s disease: can mitochondria be targeted therapeutically? Biochem Soc Trans. 2018 Aug 20;46(4):891-909.
  35. Zhang Q, Chen S, Yu S, et al. Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson’s disease. Neuropharmacology. 2016 Sep;108:238-51.
  36. Zhang Q, Zhang J, Jiang C, et al. Involvement of ERK1/2 pathway in neuroprotective effects of pyrroloquinoline quinine against rotenone-induced SH-SY5Y cell injury. Neuroscience. 2014 Jun 13;270:183-91.
  37. Zadori D, Veres G, Szalardy L, et al. Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines. J Alzheimers Dis. 2018;62(2):523-47.
  38. Available at: https://www.sciencedaily.com/terms/excitotoxicity.htm. Accessed March 4, 2020.
  39. Guan S, Xu J, Guo Y, et al. Pyrroloquinoline quinone against glutamate-induced neurotoxicity in cultured neural stem and progenitor cells. Int J Dev Neurosci. 2015 May;42:37-45.

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