Levels Of Common Deletion Research Articles

The mitochondrial DNA common deletion as a potential biomarker of cancer-associated fibroblasts from skin basal and squamous cell carcinomas

Cancer-associated fibroblasts (CAFs) are components of the tumor microenvironment and represent appealing therapeutic targets for translational studies. Conventional protein-based biomarkers for CAFs have been reported to be limited in their specificity, rendering difficult the identification of CAFs from normal fibroblasts (NFs) in clinical samples and dampening the development of CAF-targeted therapies to treat cancer. In this study, we propose the mitochondrial RNA and the mitochondrial DNA (mtDNA) common deletion (CD) as novel indicators of CAF identity. We found that cancer-activation correlated with decreased levels of the mtDNA CD, a condition not due to altered mitochondria count or cellular redox state, but potentially linked to the generalized overexpression of mtDNA maintenance genes in CAFs. Decreased mtDNA CD content in CAFs was associated with moderate to strong overexpression of mtDNA-encoded genes and to slightly improved mitochondrial function. We identified similar patterns of upregulation of mtDNA-encoded genes in independent single-cell RNA seq data obtained from squamous cell carcinoma (SCC) patients. By using the identified nucleic acids-based indicators, identification of CAFs from NFs could be improved, leading to potential therapeutic benefits in advancing translational and clinical studies.

Mitochondrial Common Deletion Level in Adipose Tissue Is Not Associated with Obesity but Is Associated with a Structural Change in Triglycerides as Revealed by FTIR Spectroscopy

Objective: Several studies have shown that mitochondrial metabolism may be disrupted if the rate of the specific 4,977 bp deletion of mitochondrial DNA (mtDNA) reaches a threshold. This study aimed to investigate the possible associations between the mtDNA4977 deletion load and obesity-related metabolic abnormalities in the adipose tissue. Methods: The study included thirty obese individuals, who underwent bariatric surgery, and twelve control subjects. mtDNA4977 deletion, adenine nucleotides, and lactate levels, which show the bioenergetic status were evaluated in visceral adipose tissues. Fourier transform infrared (FTIR) spectroscopy was used to investigate the structural variations and composition of adipose tissues in the context of deletion load. Results: There were no differences between the two groups in terms of mtDNA4977 deletion, adenine nucleotides, and lactate levels. The FTIR spectra indicated a few obesity-related alterations in adipose tissues that were not related to the mtDNA deletion load. Also, statistical analysis showed a correlation between the deletion load and a band shift of 1,744 cm−1, which assigns C = O stretching of the carbonyl group of the ester group in triglycerides and other esterified fatty acids, although it is not associated with obesity. Conclusions: Our data suggest that the mtDNA4977 deletion in visceral adipose tissues of obese individuals do not have a significant impact on the bioenergetic status. However, the increased accumulation of deletion may be associated with a specific change in the ester bond, indicating structural differences in the lipids. These findings shed light on our understanding of the tissue-specific distribution of mtDNA deletions and obesity-related adipose tissue pathogeneses.

P.198 Sex differences in a rat model of post-traumatic stress disorder (ptsd) treated with Cannabidiol oil

Age-related hearing impairment (ARHI) is the result of genetic predispositions combined with various environmental factors that affect the inner ear and accumulate during a lifetime. Several genes may be involved in presbycusis. Mitochondrial DNA common deletion levels in human cochlear tissue are related to the severity of hearing loss in individuals with presbycusis. In addition, it appears that reactive oxygen species formation and apoptosis are key events in the underlying pathology. The environmental factors contributing to presbycusis are very heterogeneous and may include, for example, smoking, exposure to loud noise, and the use of ototoxic drugs. ARHI does not follow a single pattern and may potentially be accompanied by either one or more of the following: an age-dependent loss of sensory hair cells and/or auditory nerve fibers, and degeneration of the stria vascularis.

Characterization of the neonatal phencyclidine and post-weaning social isolation dual-hit model of schizophrenia-like behavior in the rat

Age-related hearing impairment (ARHI) is the result of genetic predispositions combined with various environmental factors that affect the inner ear and accumulate during a lifetime. Several genes may be involved in presbycusis. Mitochondrial DNA common deletion levels in human cochlear tissue are related to the severity of hearing loss in individuals with presbycusis. In addition, it appears that reactive oxygen species formation and apoptosis are key events in the underlying pathology. The environmental factors contributing to presbycusis are very heterogeneous and may include, for example, smoking, exposure to loud noise, and the use of ototoxic drugs. ARHI does not follow a single pattern and may potentially be accompanied by either one or more of the following: an age-dependent loss of sensory hair cells and/or auditory nerve fibers, and degeneration of the stria vascularis.

Mitochondrial Common Deletion Level in Blood: New Insight Into the Effects of Age and Body Mass Index.

Background: Age-related decrease in mitochondrial activity has been reported in several tissues. Reactive Oxygen Species (ROS) produced from defected mitochondria lead to aging and accumulate through time. However, studies about the mitochondrial DNA mutation level in blood are contradictory. Other lifestyle factors may modify the effects of age in post-mitotic tissues such as blood. The BMI represents the sum of the various lifestyle factors.Objective: We proposed that age, obesity and mtDNA deletion are three ROS producing factors, which may interact with each other and induce senescence.Methods: In a cross-sectional study, 172 male and female volunteers without known mitochondrial diseases were selected and the presence of common mitochondrial 4977bp deletion (ΔmtDNA4977) evaluated using Nested-PCR.Results: Our results showed that a high percentage of samples (54.06%) harbor common deletion in blood. Furthermore, both BMI and the ΔmtDNA4977 levels significantly decrease with age. The chronological age, BMI and ΔmtDNA4977 reciprocally affect each other.Conclusion: Our data suggest that age affects purifying selection and BMI, which may influence the relative level of the mtDNA common deletion in blood.

Tenofovir disoproxil fumarate-associated renal tubular dysfunction

Objective:To determine whether tenofovir disoproxil fumarate (TDF)-associated renal tubular dysfunction is associated with evidence of mitochondrial injury in urine.Design:Single-centre cross-sectional observational study of HIV-positive outpatients.Methods:Biochemistry was performed on paired serum and urine samples. Mitochondrial DNA (mtDNA) was studied by real-time PCR and long-range PCR on cellular fractions of urine.Results:In total, 48 study participants were enrolled of whom half were TDF treated. Mean age was 43 years. 58% had estimated glomerular filtration rate at least 90, with no differences between ART treatment groups. Urinary phosphate wasting was common and independently associated with TDF exposure (P = 0.02). No study participants had low molecular weight proteinuria. Cellular mtDNA content in urine was heavily influenced by the cellularity of the sample. The mtDNA ‘common deletion’ mutation was detectable significantly more commonly in the urine of TDF exposed study participants compared with unexposed (13/22 TDF+ study participants (59%), 4/21 TDF− (19%), P = 0.01). Common deletion levels were not associated with age, estimated glomerular filtration rate, or urinary phosphate wasting. No mtDNA measures were associated with current or nadir CD4+ lymphocyte counts, duration of disease or antiretroviral therapy, or historical exposure to nucleoside analogue reverse transcriptase inhibitors with systemic mitochondrial toxicity.Conclusion:The presence of mtDNA mutations in the context of TDF exposure adds weight to the hypothesis that TDF-associated renal damage is at least in part mitochondrially mediated. The assessment of mtDNA markers in urine may be a feasible noninvasive investigation for TDF-treated patients.

Association between the mitochondrial DNA4977 common deletion in the hair shaft and hearing loss in presbycusis.

The aim of the present study was to examine the role of the mitochondrial (mt) DNA common deletion (CD) 4977 (mtDNACD4977) in the hair shaft in patients with presbycusis. A total of 87 individuals with presbycusis and 95 normal‑hearing controls were selected based on strict audiometric criteria. Nested polymerase chain reaction (PCR), sequencing and quantitative (q)PCR were used to examine the expression levels of mtDNACD4977 in the hair shaft in presbycusis. Nested PCR of the hair shaft demonstrated that 8/95 cases with normal hearing were found to be positive for mtDNACD4977, as compared with 59/87 cases in the presbycusis group. The mtDNACD4977 was positive in 22/43 cases with mild‑to‑moderate hearing loss, 25/31 cases with moderate‑to‑severe, severe hearing loss, and 12/13 cases with profound deafness. Statistically significant differences in mtDNACD4977 expression were identified among all of the groups (P<0.001). The sequencing and qPCR assays demonstrated a trend towards an increase in the mean CD level of mtDNACD4977 with a more severe hearing loss at 8 kHz (r=0.778, P<0.001) and all ranges of frequency (r=0.858, P<0.001). In conclusion, the present study demonstrates a correlation between mtDNACD4977 in the human hair shaft and the severity of hearing loss in presbycusis.

D-galactose-induced mitochondrial DNA oxidative damage in the auditory cortex of rats

Chronic administration of D-galactose (D-gal) is a useful method for establishing a model of natural aging in the auditory system. Previous studies have demonstrated that NADPH oxidases (NOXs) may be an important source of reactive oxygen species (ROS) in the peripheral auditory system (PAS) and cause an increase in mitochondrial DNA (mtDNA) common deletion (CD) levels in the PAS and central auditory system (CAS) of rats with D-gal-induced aging. However, the source of the ROS in the CAS and the mechanisms of age-related hearing loss (ARHL) have yet to be elucidated. In the present study, male Sprague Dawley rats were administered a daily injection of D-gal (150, 300 and 500 mg/kg, respectively) for eight weeks. All three doses of D-gal caused a significant increase in the expression of NOX2, 8-hydroxy-2-deoxyguanosine, a biomarker of DNA oxidative damage, and uncoupling protein 2, together with a decrease in the mitochondrial total antioxidant capabilities in the auditory cortex, as compared with the control rats (injected daily with the same volume of 0.9% saline for eight weeks). The levels of the mtDNA CD were also increased in the auditory cortex of the D-gal-induced aging rats. These findings suggest that both NOX- and mitochondria-associated ROS generation may contribute to mtDNA oxidative damage in the auditory cortex of the CAS of D-gal-induced aging rats. This study may provide novel insight into the development of ARHL.

The somatic common deletion in mitochondrial DNA is decreased in schizophrenia

Large deletions in mitochondrial DNA (mtDNA) can occur during or result from oxidative stress leading to a vicious cycle that increases reactive oxygen species (ROS) damage and decreases mitochondrial function, thereby causing further oxidative stress. The objective of this study was to determine if disease specific brain differences of the somatic mtDNA common deletion (4977bp) could be observed in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) compared to a control group.The accumulation of the mtDNA common deletion was measured using a quantitative assay across 10 brain regions (anterior cingulate cortex, amygdala, caudate nucleus, dorsolateral prefrontal cortex, hippocampus, nucleus accumbens, orbitofrontal cortex, putamen, substantia nigra, and thalamus).The correlation with age of the mtDNA deletion was highly significant across brain regions as previously shown. A significant decrease in the global accumulation of common deletion in subjects with SZ compared to MDD, BD, and controls was observed after correcting for age, pH, PMI, and gender. The decreases in SZ were largest in dopaminergic regions. One potential side effect of antipsychotic drugs on mitochondria is the impairment of mitochondria function, which might explain these findings.The decreased global brain mtDNA common deletion levels suggests that mitochondrial function is impaired and might be part of an overall mitochondria dysfunction signature in subjects with schizophrenia.

Common Deletion (CD) in mitochondrial DNA of irradiated rat heart.

The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rd until the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels.

The effect of overexpression of PGC-1α on the mtDNA4834 common deletion in a rat cochlear marginal cell senescence model

Aging is a natural process usually defined as a progressive loss of function with an accumulation of senescent cells. The clinical manifestations of this process include age-related hearing loss (AHL)/presbycusis. Several investigations indicated the association between a mitochondrial common deletion (CD) (mtDNA 4977-bp deletion in humans, corresponding to 4834-bp deletion in rats) and presbycusis. Previous researches have shown that peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a key regulator of mitochondrial biogenesis and energy metabolism. However, the expression of PGC-1α in the inner ear and the possible effect of PGC-1α on presbycusis are not clear. Our data demonstrated the distribution of PGC-1α and its downstream transcription factors nuclear respiratory factor-1 (NRF-1), mitochondrial transcription factor A (Tfam) and nuclear factor κB (NF-κB) in marginal cells (MCs) for the first time. To explore the role of PGC-1α in cellular senescence, we established a model of marginal cell senescence harboring the mtDNA4834 common deletion induced by d-galactose. We also found that PGC-1α and its downstream transcription factors compensatorily increased in our cell senescence model. Furthermore, the overexpression of PGC-1α induced by transfection largely increased the expression levels of NRF-1 and TFAM and significantly decreased the expression level of NF-κB in the cell senescence model. And the levels of CD, senescent cells and apoptotic cells in the cell model decreased after PGC-1α overexpression. These results suggested that PGC-1α might protect MCs in this cell model from senescence through a nuclear-mitochondrial interaction and against apoptosis. Our study may shed light on the pathogenesis of presbycusis and provide a new therapeutic target for presbycusis.

NADPH oxidase-dependent oxidative stress and mitochondrial damage in hippocampus of D-galactose-induced aging rats

Mitochondrial DNA (mtDNA) common deletion (CD) plays a significant role in aging and age-related diseases. In this study, we used D-galactose (D-gal) to generate an animal model of aging and the involvement and causative mechanisms of mitochondrial damage in such a model were investigated. Twenty 5-week-old male Sprague-Dawley rats were randomly divided into two groups: D-gal group (n=10) and control group (n=10). The quantity of the mtDNA CD in the hippocampus was determined using a TaqMan real-time PCR assay. Transmission electron microscopy was used to observe the mitochondrial ultrastructure in the hippocampus. Western blot was used to detect the protein levels of NADPH oxidase (NOX) and uncoupling protein 2 (UCP2). We found that the level of mtDNA CD was significantly higher in the hippocampus of D-gal-induced aging rats than in control rats. In comparison with the control group, the mitochondrial ultrastructure in the hippocampus of D-gal-treated rats was damaged, and the protein levels of NOX and UCP2 were significantly increased in the hippocampus of D-gal-induced aging rats. This study demonstrated that the levels of mtDNA CD and NOX protein expression were significantly increased in the hippocampus of D-gal-induced aging rats. These findings indicate that NOX-dependent reactive oxygen species generation may contribute to D-gal-induced mitochondrial damage.

Mitochondrial common deletion mutation and extrinsic skin ageing in German and Japanese women

The mitochondrial common deletion (CD) mutation is induced by oxidative stress. One main source of oxidative stress is the error-prone process of the respiratory chain located in the mitochondria. Another important source is the exposure to environmental factors, which further induces oxidative stress in the cells. For human skin, the primary damaging environmental factor is ultraviolet (UV) radiation, which is able to induce CD mutations and the characteristic extrinsic skin ageing signs. Traditionally, levels of UV exposure differ between German and Japanese populations, as tanned skin represents beauty and health in Western cultures, whereas photo-protected skin is considered ideal in Asia. We hypothesize that (i) this cultural-related UV exposure pattern might be reflected by CD concentrations in environmentally exposed skin and (ii) CD concentrations in environmentally exposed areas might be associated with the manifestation of extrinsic skin ageing. In this study, we determined the concentration of CD in skin from the neck (environmentally exposed area) and the buttock (environmentally protected area) of 22 German and 46 Japanese women between 30 and 70 years of age. We evaluated skin ageing signs by a validated clinical score, and exposure to environmental factors, such as UV exposure and smoking, was assessed using a questionnaire-based interview. Higher levels of CD were detected in neck skin than in buttock skin in both German and Japanese women. CD also increased with age in the neck skin. German women had higher CD concentrations in the neck skin than Japanese women. The CD concentrations in the buttock skin samples were similar in both populations. These findings suggest higher environmental UV exposure resulted in higher levels of CD in the skin of German women compared with Japanese women. However, only in Japanese women were the signs of extrinsic skin ageing associated with higher CD concentrations in the neck skin, in agreement with the hypothesis (ii). In German women, we did not find this latter association, which might be due to reaching a maximum level of CD, beyond which cells undergo negative selection and are lost to the population samples. In conclusion, under some conditions, there seems to be an association between the CD mutation concentration and extrinsic skin ageing, but this may be modified by cellular and tissue processes which affect the sampling rate for CD mutation concentrations and prevent a statistical association with extrinsic skin ageing.

Mitochondrial mutations and polymorphisms in psychiatric disorders.

Mitochondrial deficiencies with unknown causes have been observed in schizophrenia (SZ) and bipolar disorder (BD) in imaging and postmortem studies. Polymorphisms and somatic mutations in mitochondrial DNA (mtDNA) were investigated as potential causes with next generation sequencing of mtDNA (mtDNA-Seq) and genotyping arrays in subjects with SZ, BD, major depressive disorder (MDD), and controls. The common deletion of 4,977 bp in mtDNA was compared between SZ and controls in 11 different vulnerable brain regions and in blood samples, and in dorsolateral prefrontal cortex (DLPFC) of BD, SZ, and controls. In a separate analysis, association of mitochondria SNPs (mtSNPs) with SZ and BD in European ancestry individuals (n = 6,040) was tested using Genetic Association Information Network (GAIN) and Wellcome Trust Case Control Consortium 2 (WTCCC2) datasets. The common deletion levels were highly variable across brain regions, with a 40-fold increase in some regions (nucleus accumbens, caudate nucleus and amygdala), increased with age, and showed little change in blood samples from the same subjects. The common deletion levels were increased in the DLPFC for BD compared to controls, but not in SZ. Full mtDNA genome resequencing of 23 subjects, showed seven novel homoplasmic mutations, five were novel synonymous coding mutations. By logistic regression analysis there were no significant mtSNPs associated with BD or SZ after genome wide correction. However, nominal association of mtSNPs (p < 0.05) to SZ and BD were found in the hypervariable region of mtDNA to T195C and T16519C. The results confirm prior reports that certain brain regions accumulate somatic mutations at higher levels than blood. The study in mtDNA of common polymorphisms, somatic mutations, and rare mutations in larger populations may lead to a better understanding of the pathophysiology of psychiatric disorders.

Analysis of mitochondrial DNA variations in a Chinese family with spinocerebellar ataxia

Mitochondrial dysfunction and mitochondrial DNA (mtDNA) variations have been shown to have a role in several neurological diseases. To determine whether there is an association between mtDNA variations and spinocerebellar ataxia (SCA), we analyzed the mtDNA main control region (D-loop), as well as mtDNA content and the prevalence of the common deletion, in blood samples from members of a large Chinese family (14 individuals with SCA and 13 healthy individuals). All 14 individuals with SCA were genotyped as SCA3. Thirteen mtDNA haplotypes were identified among the 27 subjects. We detected no mutations in the mtDNA D-loop region and found no significant differences in mtDNA copy number or common deletion level between patients and their healthy relatives. Contrary to some previous reports, our study showed that mtDNA variations seem to be a rare event in individuals with SCA3.

Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

BackgroundMitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiation toxicity.MethodsPeripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively). Extracted DNA was analyzed by real-time PCR method.ResultsAverage 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048). Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age.ConclusionsmtDNA and CD content may be considered as predictive factors to radiation toxicity.

Contribution of common deletion to total deletion burden in mitochondrial DNA from inner ear of d-galactose-induced aging rats

Mitochondrial DNA (mtDNA) mutations, especially deletions, have been suggested to play an important role in aging and degenerative diseases. In particular, the common deletion in humans and rats (4977 bp and 4834 bp deletion, respectively) has been shown to accumulate with age in post-mitotic tissues with high energetic demands. Among numerous deletions, the common deletion has been proposed to serve as a molecular marker for aging and play a critical role in presbyacusis. However, so far no previous publication has quantified the contribution of common deletion to the total burden of mtDNA deletions in tissues during aging process. In the present study, we established a rat model with various degrees of aging in inner ear induced by three different doses of d-galactose ( d-gal) administration. Firstly, multiple mtDNA deletions in inner ear were detected by nested PCR and long range PCR. In addition to the common deletion, three novel mtDNA deletions were identified. All four deletions, located in the major arc of mtDNA, are flanked by direct repeats and involve the cytochrome c oxidase (COX) subunit III gene, encoded by mtDNA. Additionally, absolute quantitative real-time PCR assay was used to detect the level of common deletion and total deletion burden of mtDNA. The quantitative data show that the common deletion is the most frequent type of mtDNA deletions, exceeding 67.86% of the total deletion burden. Finally, increased mtDNA copy number, reduced COX activity and mosaic ultrastructural impairments in inner ear were identified in d-gal-induced aging rats. The increase of mtDNA replication may contribute to the accelerated accumulation of mtDNA deletions, which may result in impairment of mitochondrial function in inner ear. Taken together, these findings suggest that the common deletion may serve as an ideal molecular marker to assess the mtDNA damage in inner ear during aging.

Distinct profile of the mitochondrial DNA common deletion in benign skin lesions

Mutations of mitochondrial (mt) DNA, particularly the 4977 bp long common deletion, are increased in aging tissues and preferentially found in chronologically and photoaged skin. Mutations of human mitochondrial DNA (mtDNA) have also been identified in malignant tumors of the skin and of other organs. However, benign skin lesions have not yet been investigated. We analyzed the frequency of the common deletion in 27 benign skin lesions [8 seborrheic keratoses (SK), 5 epidermal nevi (EN), 14 solar lentigos (SL)] by quantitative real-time PCR, because SK and especially SL have been related to (photo)aged skin. All SK and four of five EN displayed reduced common deletion levels compared with adjacent normal skin. In contrast, 50% of SL revealed a higher percentage of the common deletion than the adjacent normal skin, and some SL showed very high absolute common deletion levels up to 14% of total mtDNA. Our results show that the amount of the common deletion is significantly different in benign skin lesions and raise further questions regarding the pathogenesis of SL and its possible role as a precursor lesion of SK.

Major arc mitochondrial DNA deletions in cytochrome c oxidase-deficient human cochlear spiral ganglion cells

Conclusions: This study suggests that cytochrome c oxidase subunit 3 (COX 3) expression is diminished in spiral ganglion cells from individuals with presbycusis. In addition to the mitochondrial DNA (mtDNA) common deletion (CD), other deletions involving the mtDNA major arc contribute to the observed deficit in COX 3 expression. Objectives: To assess COX 3 deficiency in spiral ganglion cells from individuals with presbycusis and to determine whether deletions other than the CD contribute to this deficiency. Methods: COX 3 immunofluorescence staining of archival human temporal bone tissue sections from individuals with presbycusis and from age-matched normal-hearing individuals was performed and the intensity of spiral ganglion cell immunostaining was measured. Single COX 3-deficient spiral ganglion cells were isolated by laser microdissection (LMD) and the DNA was analyzed with duplex real-time PCR assays to assess the CD level and the total mtDNA major arc deletion level. Results: A statistically significant difference (p = 0.021) in the mean intensity of COX 3 immunofluorescence staining of spiral ganglion cells was observed between individuals with presbycusis and normal-hearing controls. The total mtDNA major arc deletion level was greater than the CD level in COX 3-deficient spiral ganglion cells.

Quantification of the mitochondrial DNA common deletion in presbycusis

This study was conducted to evaluate the association between the mitochondrial DNA (mtDNA) common deletion (CD) level in cochlear tissue and the severity of hearing loss in individuals with presbycusis. Nineteen individuals with presbycusis, ranging from 60 to 87 years of age, who met strict audiometric criteria were compared with four age frequency-matched normal hearing controls ranging from 51 to 76 years of age. Five additional normal hearing individuals, ranging from 9 to 50 years of age, were also studied. A duplex real time polymerase chain reaction assay was used to quantify the mtDNA in archival cochlear tissue samples. Linear regression models were used for comparison of the CD level between groups. The presbycusis group had a mean CD level of 32% with a standard deviation of 14%, and the normal hearing age matched control group had a mean CD level of 12% with a standard deviation of 2%. This difference in CD levels reached statistical significance (P = .011) and remained significant after adjusting for any differences in age between the two groups (age-adjusted P = .007). Furthermore, there was evidence for a significant association between the CD level and the severity of hearing loss based on audiometric thresholds at 8 kHz (r = 0.44, P = .034; age-adjusted partial correlation = 0.55, P = .007). For the first time, to our knowledge, these results demonstrate a relationship between quantitatively measured levels of the CD in human cochlear tissue and the severity of hearing loss in individuals with presbycusis. Laryngoscope, 2009.