Increased oxidative stress and coenzyme Q10 deficiency in centenarians

Abstract

Aging populations are expanding worldwide, and the increasing requirement for nursing care has become a serious problem. Furthermore, successful aging is one of the highest priorities for individuals and societies. Centenarians are an informative cohort to study and inflammation has been found to be a key factor in predicting cognition and physical capabilities. Inflammation scores have been determined based on the levels of cytokines and C reactive protein, however, serum antioxidants and lipid profiles have not been carefully examined. We found that the redox balance of coenzyme Q10 significantly shifted to the oxidized form and levels of strong antioxidants, such as ascorbic acid and unconjugated bilirubin, decreased significantly compared to 76 year old controls, indicating an increased oxidative stress in centenarians. Levels of uric acid, an endogenous peroxynitrite scavenger, remained unchanged, suggesting that centenarians were experiencing moderate, chronic inflammatory conditions. Centenarians exhibited a hypocholesterolemic condition, while an increase in the ratio of free cholesterol to cholesterol esters sug gests some impairment of liver function. Serum free fatty acids and monoenoic acid composition, markers of tissue oxidative damage, were significantly decreased in centenarians, indicating an impairment in the tissue repair system. Despite an elevation of the coenzyme Q10 binding protein Psap, serum total coenzyme Q10 levels decreased in centenarians. This suggests a serious deficiency of coenzyme Q10 in tissues, since tissue levels of coenzyme Q10 significantly decrease with age. Therefore, coenzyme Q10 supple mentation could be beneficial for centenarians.

Modulation of Coenzyme Q10 content and oxidative status in human dermal fibroblasts using HMG-CoA reductase inhibitor over a broad range of concentrations. From mitohormesis to mitochondrial dysfunction and accelerated aging

“…In fact, decrease in CoQ 10 content is known to occur in conditions associated both with oxidative stress and mitochondrial dysfunction such as degenerative pathologies and in physiological conditions during the aging process with organ specific differences [11] both in animal models [12] and in humans [13,14]. Moreover, CoQ 10 supplementation has been shown to be effective in reverting senescent phenotype features in in vitro models as well as in animal and human interventions studies.…”

Increased oxidative stress and renal injury in patients with sepsis

“…Psap is the coenzyme Q10 binding and transfer protein present in both the extracellular and intracellular space. ( 27 ) We have observed an increase in plasma (serum) levels of Psap under oxidative stress conditions such as in centenarians ( 10 ) and patients with post-cardiac arrest syndrome, ( 25 ) ALS (unpublished observation), and Parkinson’s disease (unpublished observation). Therefore, it was unexpected that Psap levels in patients with sepsis were significantly lower than those in healthy controls (Table 1 ).…”

“…( 12 , 13 ) Elevation of %CoQ10 was confirmed in patients with hepatitis, cirrhosis, hepatoma, ( 16 ) Parkinson’s disease, ( 22 ) juvenile fibromyalgia, ( 23 ) amyotrophic lateral sclerosis (ALS), ( 24 ) and post-cardiac arrest syndrome, ( 25 ) and in newborn babies ( 26 ) and centenarians. ( 10 )…”

“…( 8 , 9 ) In this study, we measured plasma levels of the above antioxidants in patients with sepsis in comparison to age-matched healthy controls. ( 10 ) We focused on the percentage of oxidized form of coenzyme Q10 in total coenzyme Q10 because oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former ( 11 ) and plasma ubiquinol-10 is vulnerable to oxidation. ( 12 , 13 )…”

Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges

“…While an average healthy adult's body contains 0.5 to 1.5 g of CoQ10, its levels may be compromised by different factors (Bhagavan & Chopra, 2006). Deficiency can occur as a result of physiopathologic conditions such as acquired or genetic alterations in metabolism or biosynthesis (Alcázar-Fabra, Navas, & Brea-Calvo, 2016;Quinzii, DiMauro, & Hirano, 2007), an inadequate intake of CoQ10 or its dietary precursors (Potgieter et al, 2013), aging and oxidative stress that leads to an excessive utilization of the molecule (Nagase, Yamamoto, Matsumoto, Arai, & Hirose, 2018), or due to a combination of these factors. A suboptimal CoQ10 intake led to deficiencies when certain conditions or drugs were present.…”