The Paradox of Coenzyme Q10 in Aging
Abstract
:1. Introduction
1.1. CoQ Biosynthesis
1.1.1. Quinone Synthesis
1.1.2. Polyisoprenyl Tail Synthesis
1.1.3. Attachment of the Ring/Chain
1.1.4. Next Steps of CoQ Biosynthesis-Ring Modifications
1.1.5. Other Mitochondrial Proteins Involved in CoQ Biosynthesis
1.1.6. Complex Q
1.2. Functions of CoQ
1.2.1. The Role of CoQ in the Mitochondrial Respiratory Chain
1.2.2. The Antioxidant Capacity
1.2.3. Other Controversial Functions
1.3. Pathologic Conditions with Decreased Levels of CoQ
1.3.1. Primary CoQ10 Deficiencies
1.3.2. Secondary CoQ10 Deficiencies
2. Long-Life Animal Models with CoQ Deficiency: Potential Mechanisms
2.1. Worm Models
2.2. Mouse Models
3. Dietary Supplementation of CoQ10 during Aging
3.1. Changes in CoQ Biosynthesis during Aging
3.2. CoQ10 Supplementation in Aging: Effects on Life span and Longevity
3.3. Reversal of Age-Related Changes by CoQ10 Supplementation
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Model | Strain | Age, Gender, n | CoQ form (Daily Dose/Conc), Treatment Duration | Diet/Food | Effect on Longevity | Ref |
---|---|---|---|---|---|---|
Caenorhabditis elegans | N2 Bristol wild-type | Egg, n = 88–105 | Water-soluble CoQ10 1 (dose) | Nematode growth medium (NGM) with E. coli OP50 | No effect | [187] |
L1, n = 96–98 | CoQ10 (50g/mL) | NGM with E. coli OP50 | Average life span extended by 6% | [188] | ||
CoQ10 (150g/mL) | NGM with E. coli OP50 | Average life span extended by 18% | [188] | |||
Clk-1 mutant | Egg, n = 88–105 | Water-soluble CoQ10 1 (dose), 24 h | NGM with E. coli OP50 | No effect | [187] | |
Eggs, n = 100 | Different engineered Escherichia coli strains producing either CoQ6 to CoQ10 | NGM with different engineered E. coli strains or E. coli OP50 (which produce CoQ8) | Median adult life span increased by 19% but only with CoQ10-producing bacteria | [118] | ||
Mev-1 (kn1) mutant | L1, n = 96–98 | CoQ10 (50g/mL) | NGM with E. coli OP50 | Average life span increased by 13% | [132] | |
CoQ10 (150g/mL) | NGM with E. coli OP50 | Average life span increased by 19% | ||||
Mouse (Mus musculus) | C57BL/6 | 3.5 months old, n = 50 | CoQ10 (93 mg/kg of bw) | ad libitum Purina diet 5001 | No effect | [157] |
CoQ10 (371 mg/kg of bw) | ad libitum Purina diet 5001 | No effect | [157] | |||
C57/B17 | 2 m old, male, n = 43 | CoQ10 (10 mg/kg of bw) | normal animal diet | No effect | [170] | |
C57BL/6 C3H (B6C3F1) | 14 m old, male n = 60 | CoQ10 (100 mg/kg) | AIN93 diet | No effect | [169] | |
Rat (Rattus norvegicus) | Sprague–Dawley | From pregnancy, male, n = 75 | CoQ10 (10 mg/kg) | normal animal diet | No effect | [170] |
Wistar | 28 d old (weaning), male, n = 43 | CoQ10 (2.5 mg/kg of bw) | AIN93 diet but with 8% sunflower oil or virgin olive oil as unique dietary fats | Median life span increased by 11.7%. | [180] | |
28 d old (weaning), male, n = 22–25 | CoQ10 (2.5 mg/kg of bw) | AIN93 diet with sunflower oil as unique dietary fat (4%) | Increased median life span by 25.5% | [171] | ||
AIN93 diet with fish oil as unique dietary fat (4%) | No effect | [171] | ||||
AIN93 diet with virgin olive oil as unique dietary fat (4%) | No effect | [171] |
Model | Strain, Age, Sex | CoQ form (Dose), Duration | Diet/Food | Tissues, Organs or Systems (Sample Size Per Group) | Consequences in Age-Related Changes | Ref |
---|---|---|---|---|---|---|
C. elegans | N2 Bristol wild-type, Egg | Water-soluble CoQ10 1 | NGM containing 200 μg/mL streptomycin with E. coli OP50, 24 h | Nervous system | No effect on pharyngeal contraction and defecation rate. | [187] |
N2 Bristol wild-type, L1 | CoQ10 (50 or 150 g/mL) | With a lawn of E. coli OP50 | - | Reduced O2− in the presence of succinate, although in a slight manner. | [131] | |
Clk-1 mutant, Egg | Water-soluble CoQ10 1 (0.1, 1, or 10 μM) | NGM containing 200 μg/mL streptomycin with E. coli OP50, 24 h | Nervous system | Increased pharyngeal pumping rate and defecation rate slowed in a dose-dependent manner, with comparable values found in wild-type strains. | [187] | |
Different engineered E. coli strains producing CoQ6 to CoQ10 | NGM with different engineered strains or the OP50 strain of E. coli | - (100) | Bacteria containing CoQ6, CoQ7 or CoQ10 decreased complex I-dependent respiration rates compared to those containing CoQ8 or CoQ9. Bacteria containing CoQ7 or CoQ10 decreased complex II-dependent respiration rates compared to those fed on bacteria containing vitamin K12, CoQ6 or CoQ8. | [228] | ||
Mouse (Mus musculus) | C57BL/6, 3.5 m old, male, | CoQ10 (0.072 or 0.281%, w/w), 16/22 m of age | ad libitum Purina diet 5001 | Liver, heart, skeletal muscle and brain (2–6) | No effect on enzymatic antioxidant defenses (SOD, catalase and GPX activities). No effect on protein oxidative damage (carbonyl content). No effect on mitochondrial Reactive Oxygen Species (ROS) production. No effect on glutathione redox state. No effect on mitochondrial function (mtETC complexes activities). | [157] |
C57BL/6NCr, 15/6 m old, male, | Water-soluble CoQ10 1 (150 μM) via drinking water | Standard chow diet | Brain (motor cortex) (6–9) | Restored aging-associated decreases in mitochondrial function (OCR). Restored aging-associated motor function, phosphorylated α-synuclein and glutamate transporter 1 levels. | [229] | |
SAMP1, 4 wk old, male and female | CoQ10 (0.2%, w/w), 10/12/14/16 m | Standard laboratory mouse diet | General (9–11) | No effect on senescence evaluated by the grading system by Hosokawa et al., 1984. | [211] | |
Urine (9–11) | No effect on oxidative damage (acrolein-lysine adduct and OhdG). | |||||
Brain (9–11) | No effect on senile amyloid deposition rate. | [211] | ||||
CoQ10 H2 (0.2%, w/w), 10/12/14/16 m | General (10) | Slowed senescence evaluated by the grading system. | [211] | |||
Urine (10) | No effect on oxidative damage (acrolein-lysine adduct and OhdG). | [211] | ||||
Brain (10) | No effect on senile amyloid deposition rate. | [211] | ||||
SAMP1/Sku Slc, 4 wk old, female | CoQ10 H2 (0.3%, w/w), 2/7/13/ and 19 m of age | CE-2 | General (11–20) | Slowed degree of senescence 2. Slowed the rate of age-related hearing loss. | [210] | |
Liver (11–20) | Prevented age-related decreases in the expression of sirtuin gene family members and increased intracellular cyclic AMP (cAMP) levels. Maintained mitochondrial biogenesis and oxidative metabolism by maintaining PPARγ coactivator (PGC)-1α activated. Maintained enzymatic antioxidant defenses (SOD and isocitrate dehydrogenase [IDH]2). Increased mitochondrial function (complex I activity). Decreased protein, lipid and DNA oxidative damage (protein carbonyls, MDA and apurinic/apyrimidinic sites). Increased the GSH:GSSG ratio. | [210] | ||||
Rat (Rattus novergicus) | Sprague–Dawley, 14 m old, male | CoQ10 (0.324%, w/w), 13 wk | NIH-31 diet | Blood (8) | Increased the GSH:GSSG ratio. | [156] |
Liver (8) | No effect on protein oxidative damage (protein carbonyls). No effect on enzymatic antioxidant defense (catalase, SOD and GPX). | [156] | ||||
Heart and Brain | No effect on lipid oxidative damage (hydroperoxides). No effect on mitochondrial ROS (H2O2) production. | [156] | ||||
Skeletal muscle | No effect on lipid oxidative damage (hydroperoxides). Decreased protein oxidative damage (protein carbonyls) at mitochondria. No effect on mitochondrial ROS (H2O2) production. No effect on enzymatic antioxidant defense (catalase, SOD and GPX). | [156] | ||||
Wistar, 28 d old (weaning) male | CoQ10 (0.005%, w/w), 6/24 m of age | AIN93 diet with sunflower oil as unique fat source (4%) | Urine (6) | Reduced aging-associated increase in urinary F2-isoprostanes. | [174] | |
Pancreas (6) | Improved endocrine pancreas structure, in particular β-cell mass. | [175] | ||||
Bone (6) | Prevented aging-associated bone mass loss decline. | [174] | ||||
Alveolar bone (6) | Attenuated aging-associated alveolar bone loss. | [173] | ||||
Gingivae (6) | Increased antioxidant enzymatic defenses (antioxidant enzyme gene expression). Increased mitochondrial biogenesis markers. | [173] | ||||
AIN93 diet with fish oil as unique fat source (4%) | PBMCs | Reduced DNA oxidative damage markers (DNA strand breaks) in 24-m-old rats. | [182] | |||
Urine | Reduced lipid oxidative damage markers (F2-isoprostanes) in 6-m-old rats. | [182] | ||||
Pancreas | No effect on structural alterations in exocrine compartment. | [175] | ||||
Bone | Increased bone mass density in 24-m-old rats. | [182] | ||||
Alveolar bone | No effect on aging-associated alveolar bone loss. | [173] | ||||
Gingivae | No effect on mitochondrial biogenesis markers. | [173] | ||||
AIN93 diet with virgin olive oil as unique fat source (4%) | Urine | No effect on lipid oxidative damage (F2-isoprostanes) markers. | [174] | |||
Pancreas | No effect on histopathological alterations. | [175] | ||||
Bone | No effect on aging-associated bone mass density loss. | [174] | ||||
Alveolar bone | No effect on aging-associated alveolar bone loss. | [173] | ||||
Gingivae | No effect on mitochondrial biogenesis markers. No effect on enzymatic antioxidant defense | [173] | ||||
CoQ10 (0.005%, w/w), 6/12 m | AIN93 diet but with 8% of sunflower oil as fat source | Heart (8) | Attenuated an aging-associated increase in lipid oxidative damage (hydroperoxides). | [176] | ||
CoQ10 (0.062%, w/w), 6/12 m of age | AIN93 diet but with 8% of sunflower oil as fat source | Liver (8) | Decreased cytosolic and membrane-bound NQO1 activity. | [184] | ||
Brain (8) | Decreased cytosolic and membrane-bound NQO1 activity | [184] | ||||
AIN93 diet but with 8% of virgin olive oil as fat source | Liver (8) | Decreased cytosolic and membrane-bound NQO1 activity. | [184] | |||
Brain (8) | Decreased cytosolic and membrane-bound NQO1 activity. | [184] | ||||
CoQ10 (0.005%, w/w), 6/12/18/24 m of age | AIN93 diet but with 8% of sunflower oil as fat source | Blood (8) | Decreased DNA oxidative damage markers (DNA strand breaks) in PBMCs in 18- and 24-m-old rats. | [180] | ||
CoQ10 (0.005%, w/w), 6/12/24 m of age | AIN93 diet but with 8% of sunflower oil as fat source | Heart (20) | Decreased lipid oxidative damage (hydroperoxides) in 12- and 14-m-old rats. | [213] | ||
Liver (8) | Prevented an aging-associated decrease in glutathione-S-transferase (GST) activity but Se-dep GPX was not clearly affected. No effect on basal lipid oxidative damage markers (hydroperoxides) but attenuated formation against AAPH in old rats. | [183] | ||||
CoQ10 (0.005%, w/w) 6/24 m of age | AIN93 diet with 8% of sunflower oil as fat source | Blood (20) | Increased non-enzymatic antioxidant defenses (α-tocopherol and retinol) and total antioxidant capacity in aged rats. Decreased DNA oxidative damage markers (DNA strand breaks) in PBMCs in young rats. | [179] | ||
Liver | Prevented an aging-associated increase in lipid oxidative damage markers (hydroperoxides). Increased non-enzymatic antioxidant defenses (α-Tocopherol). Prevented an aging-associated decrease in enzymatic antioxidant defenses (catalase activity). | [178] | ||||
Skeletal muscle | Increased non-enzymatic antioxidant defenses (α-Tocopherol) in young rats but attenuated its aging-associated increase. Reduced lipid oxidative damage markers (hydroperoxides) at any age. Prevented an aging-associated increase in enzymatic antioxidant defenses (catalase activity). | [178] | ||||
Heart | Increased non-enzymatic antioxidant defenses. Partially prevented an age-associated mitochondrial function (mtETC II and III and COX were decreased). Prevented an age-associated increase in lipid and DNA oxidative damage in mitochondria (deleted mtDNA and hydroperoxides). Improved mitochondrial ultrastructure (area, perimeter, cristae density) in aged rats. | [181] | ||||
Brain | Increased non-enzymatic antioxidants (α-tocopherol) at mitochondria. Decreased mitochondrial ROS production. Decreased enzymatic antioxidant defenses (GPX content) in cytosol. Increased mitochondrial function (mtETC complex I, IV and III activities) in young rats, but this decreased (complex I activity) in aged rats. Decreased oxidative DNA and lipid damage markers at mitochondria (hydroperoxides and deleted mtDNA). | [178] |
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Díaz-Casado, M.E.; Quiles, J.L.; Barriocanal-Casado, E.; González-García, P.; Battino, M.; López, L.C.; Varela-López, A. The Paradox of Coenzyme Q10 in Aging. Nutrients 2019, 11, 2221. https://doi.org/10.3390/nu11092221
Díaz-Casado ME, Quiles JL, Barriocanal-Casado E, González-García P, Battino M, López LC, Varela-López A. The Paradox of Coenzyme Q10 in Aging. Nutrients. 2019; 11(9):2221. https://doi.org/10.3390/nu11092221
Chicago/Turabian StyleDíaz-Casado, M. Elena, José L. Quiles, Eliana Barriocanal-Casado, Pilar González-García, Maurizio Battino, Luis C. López, and Alfonso Varela-López. 2019. "The Paradox of Coenzyme Q10 in Aging" Nutrients 11, no. 9: 2221. https://doi.org/10.3390/nu11092221