HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:360-364 (2008)
© 2008 The Gerontological Society of America

Age-Related Correlation Between Antioxidant Enzymes and DNA Damage With Smoking and Body Mass Index

Parvathi Kumara Reddy Thavanati, Kodanda Reddy Kanala, Aurora Escoto de Dios and Jose Maria Cantu Garza

1 Instituto de Genética, Departamento de Biología Molecular y Genomica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.
2 Department of Anthropology, School of Biological & Earth Sciences, Sri Venkateswara University, Tirupati, India.
3 Instituto de Biología Molecular en Medicina, Departamento de Biología Molecular y Genomica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.

Address correspondence to Parvathi Kumara Reddy Thavanati, PhD, DSc, Instituto de Genética, Departamento de Biología Molecular y Genomica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Puerta 7, Edificio P, Nivel II, Col. Independencia, Guadalajara. Jalisco. Código Postal: 44340. México. E-mail: tpkreddy{at}yahoo.com; reddy.parvathi{at}mail.cucs.udg.mx


   Abstract
Top
 Abstract
Method
 Results
 Discussion
 References
 
To understand whether oxidants contribute to the initiation and/or promulgation toward aging, the present study has been undertaken on 220 healthy male volunteers aged 20–80 years selected from the defined electoral area (suburbs of Tirupati, Andhra Pradesh, India) to evaluate the concentrations of free radicals (superoxide anion, hydrogen peroxide), lymphocyte antioxidant enzymes (glutathione S-transferase, superoxide dismutase, catalase), and DNA damage in relation to obesity and smoking (lifestyles). A two fold increase of lymphocyte free radical generation (DNA damage) was observed in older age groups with a reduced antioxidant potential, forming a link between cigarette smoking and oxidative stress represented by an antioxidant imbalance. Body mass index had a positive relationship with oxidative stress, but antioxidant levels did not vary with body mass index. The findings conclude that free radical–mediated oxidative stress and DNA damage accelerate with lifestyle variations under reduced antioxidant potential.

Key Words: Aging • Antioxidants • DNA damage • Smoking • Obesity

THE oxidative stress hypothesis of aging (or the free radical hypothesis as it was first proposed) is currently one of the most popular explanations of how aging occurs at the biochemical level (1). The basic tenet of the oxidative stress hypothesis is that the age-related loss of physiological function and aging are caused by the progressive and irreversible accumulation of oxidative damage (2).

Individuals are exposed to oxidants, both exogenous as well as endogenous, from birth (3,4). An increase in oxidant generation among older groups (5) affected them with a number of age-related degenerative diseases (6) such as cancer, cardiovascular disease, immune system decline, brain dysfunction, and cataracts (7). The increasing incidence of these diseases in an age-related manner may be due to a decline in the action of the antioxidant defenses and repair systems that protect the biomolecules against oxidation (8).

The possible role of free radicals in the aging process has been the subject of considerable attention recently (9). Studies on insects and mammals show that the formation rate of superoxide anion and hydrogen peroxide increased in the later part of life (10). As a result, the oxidative damage products such as protein carbonyls, lipofuscin, n-pentane exhalation, and lipid peroxidation were also elevated with advancing age (11,12). Some evidence suggests that an increased production of reactive oxygen species and/or a decreased efficiency of antioxidant defense systems are associated with aging (13,14). In this regard, antioxidants have evolved to combat the oxidant load and are believed to decrease the attacks on DNA by free radicals and thus protect against mutations that cause disease status (1,5,15–17).

Apart from the natural biological process of aging, it has also been postulated that variation in the environment (industrial and urban) and lifestyle measures act as stimulants of free radical generation, DNA damage, and reduced antioxygenic potential and play an important role in the health and longevity of human populations (4,12,16,18,19). Among the lifestyle measures, smoking and obesity took prime importance regarding the health of an individual. DNA damage was observed to be significantly higher among smokers (20) and was a source of mutagens of cancer, heart disease, and premature deaths (21), whereas obesity led to a higher oxidative stress contributing to obesity-associated diseases such as atherosclerosis, diabetes mellitus, and arterial hypertension (22) with depletion in the total antioxidant levels (23).

Although studies exist on different animal and human populations to show the effects of free radical generation and oxidative DNA damage in various disease conditions as well as on toxicity, data on the process of aging with regard to oxidative stress, antioxidants in the presence of some of the lifestyle variables in human populations is lacking, particularly in India. Therefore, the present study aimed to evaluate the correlation between antioxidant enzymes—glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT)—and DNA damage with smoking and body mass index (BMI) in men among different age groups (younger to older).


   METHOD
Top
 Abstract
 Method
Results
 Discussion
 References
 
The study population consisted of 220 healthy male volunteers aged 20–80 years selected from the defined electoral area (suburbs of Tirupati, Andhra Pradesh, India) who were noninstitutionalized and living independently without requiring any daily care and nursing support (free of any kind of medication such as steroid, diuretic, anticonvulsant, antidepressant, antibiotic, antimetabolite, nonsteroidal anti-inflammatory, as well as nonintegrator and/or vitamin supplementation). Participants were excluded if they had diabetes, autoimmune diseases, neurodegenerative diseases, cardiovascular diseases, infections, cancer, Crohn's disease, acrodermatitis enteropathica, kidney disease, liver disease, sickle cell anemia, chronic skin ulcerations, and/or endocrine disorders. The objectives of the study were clearly explained to the participants, and the individuals were neither compelled to participate in the survey nor subjected to any kind of risk and provided consent before participating in the study. Information on the age, smoking status, and anthropometric measurements such as height, weight, and circumferences of the waist and hip were collected from each participant. BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). Obese was defined as BMI > 25 kg/m2. Waist to hip ratio (WHR) was calculated from the circumferences of waist and hip. All the participants were nonvegetarians.

In the morning, venous blood (10 mL) samples were collected from all participants into disposable vials containing EDTA. Lymphocytes were separated from the whole blood by the dextran sedimentation technique (24). Protein content of the lymphocytes was estimated as per the standard procedure.

Techniques: Free Radicals
Superoxide anion.-- Superoxide anion can reduce nitroblue tetrazolium (NBT) to the insoluble formazan (25). The ability to reduce NBT was assayed by incubating lymphocytes with 0.1% NBT dissolved in phosphate-buffered saline for 20 minutes at 27°C. The assay was terminated by adding 0.6 mL of glacial acetic acid, and the extracted NBT dye was read at 560 nm.

Hydrogen peroxide.-- Hydrogen peroxide released by lymphocytes was estimated by the horseradish peroxidase method (26). Phenol red solution (1%, 0.5 mL) containing peroxidase enzyme (3.75 units per assay) was added to the lymphocytes and was incubated at 37°C for 20 minutes. The reaction was terminated by adding CAT (150 units per assay), and the optical density readings were taken at 610 nm. Lymphocyte cells (1 x 106 per assay) were taken both for superoxide anion and H2O2 assay.

Techniques: Lymphocyte Antioxidants
GST.-- GST activity was measured according to the method described by Habig and colleagues (27) using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate and glutathione as a cosubstrate. The reaction mixture in a 3 mL cuvette contained 1.0 mL of the phosphate buffer (pH 6.5), 0.1 mL of CDNB (30 mM), and 0.1 mL of glutathione (30 mM); the volume was adjusted to 2.9 mL with distilled water. The reaction mixture was preincubated at 37°C for 5 minutes. Reaction was initiated by adding 0.1 mL of the enzyme and was monitored spectrophotometrically by the increase in absorbance at 340 nm (GST-catalyzed formation of CDNB–glutathione producing a dinitrophenyl thioether). GST activity is defined as the amount of enzyme producing 1 µmol of CDNB–glutathione conjugate/min/mg protein under the conditions of the assay.

SOD.-- SOD activity was assayed according to the method of Misra and Fridovich (28). The assay medium contained 50 mM sodium carbonate, bicarbonate buffer (pH 9.8), 0.1 mM EDTA, and 0.6 mM adrenaline in a total volume of 3 mL. Adrenaline was the last component to be added, and the adrenochrome formed in 4 minutes was recorded at 470 nm. SOD activity was expressed in unit (the amount of enzyme needed to cause 50% inhibition of adrenaline autoxidation) per minute per milligram protein.

CAT.-- The CAT assay was carried out by the method described by Beer and Sizer (29). The decomposition of H2O2 was followed directly by measuring the decrease in absorbance at 240 nm. CAT activity is expressed as units of H2O2 decomposed per minute per milligram protein.

DNA Damage
DNA was extracted from lymphocytes as per the procedure specified by Hoar (24). Thiobarbituric acid (TBA) assay for DNA damage. Sugar fragments consist of compounds that carry one or several carbonyl functions, for example, 2-deoxyguanosine-5-aldehyde, that have been mistaken for malondialdehyde (MDA) because they give a very similar 2-thiobarbituric acid reaction (30). One aliquot of the DNA solution was mixed with one aliquot of 0.6% 2-thiobarbituric acid. The contents were heated at 90°C for 20 minutes, and the red color developed was measured at 537 nm. The values were expressed as nmol of MDA equivalents per milligram DNA.

The data were processed for statistical analysis including analysis of variance (ANOVA), correlation coefficient, and multiple regressions by using the standard statistical package SPSS-10, and p values <.05 were regarded as statistically significant.


   RESULTS
Top
 Abstract
 Method
 Results
Discussion
 References
 
The study participants were divided into four age groups: young (<40 years); middle-aged (40–54 years); old (55–69 years); very old (≥70 years). Mean values of anthropometry, free radical generation, DNA damage, and antioxidant enzyme levels in different ages were tested by one-way ANOVA and presented in Tables 1 and 2. Anthropometric measurements (except waist circumference and WHR) did not show significant variation within the age groups. Free radical generation, DNA damage, and antioxidant enzymes (GST and SOD) were found to have significant association with age. The patterns of age and height were nearly constant across the entire age span. Weight, circumferences of waist and hip, BMI, and WHR increased from age 20 to 54 years, and then dropped. The generation of free radicals, that is, superoxide anion and H2O2 showed a progressive increase from the younger to very old age groups, whereas the increase in DNA damage was up to age 69 years only. In contrast, antioxidant enzyme levels demonstrated a gradual decrease from the younger to the very old age groups.


View this table:
[in this window]
[in a new window]

  		Table 1. Values (Mean ± SD) for Anthropometry in Different Age Groups.

 

View this table:
[in this window]
[in a new window]

  		Table 2. Values (Mean ± SD) for Free Radical Generation, DNA Damage (MDA of Lymphocytes) and Antioxidant Enzyme Levels in Different Age Groups.

 
Partial correlation coefficients were calculated for the free radical generation, DNA damage, and antioxidants with BMI, WHR, and cigarette smoking (Table 3). Cigarette smoking had a statistically significant positive correlation with free radicals and DNA damage and had an inverse correlation with the antioxidants. BMI had a significant positive correlation with O2– and H2O2, but had no relation with DNA damage and antioxidants, whereas WHR was found to have an insignificant relationship with free radicals, DNA damage, and the antioxidants.


View this table:
[in this window]
[in a new window]

  		Table 3. Partial Correlation Coefficients for Free Radical Generation, DNA Damage, and Antioxidants with Cigarette Smoking, BMI, and WHR Controlled for Age.

 
Regression equations may be used as predictions of free radicals, DNA damage, and antioxidant enzyme levels that take age, BMI, WHR, and smoking status into account (Table 4). Cigarette smoking and age account for a high percentage of variation in free radicals and DNA damage (positive) and antioxidants (negative), whereas BMI serves as a moderate predictor of free radicals, DNA damage, and antioxidants.


View this table:
[in this window]
[in a new window]

  		Table 4. Predictive Equations for Free Radical Generation, DNA Damage, and Antioxidants.

 

   DISCUSSION
Top
 Abstract
 Method
 Results
 Discussion
References
 
There has been a great deal of controversy over whether the oxidation of DNA increases with age. Most of the studies on animals have revealed a significant increase in DNA oxidation levels with age (31,32), but an equal number have reported an insignificant change (33,34). One of the molecular theories of aging is that DNA accumulates errors (oxidative damage leading to mutations) that shorten life span (35–37). Damage to DNA from endogenous mutagens is likely to be critical for both aging and cancer (38,39). The free radical theory of aging suggests that the main endogenous mutagens are oxidants coming from partial oxygen reduction or products of lipid peroxidation (40). Consequently, the accumulation of free radical–mediated damage might be a major cause of the physiological changes associated with aging and cancer.

A significant twofold increase of lymphocyte free radical generation (O2– and H2O2) and DNA damage (measured in the form of nmol MDA equivalents/mg DNA) in the older over the younger participants (Table 2) (5) in the present study indicates that the old people were more susceptible to oxidative stress (41), and our results are consistent with the general definition of aging as the progressive accumulation of changes responsible for the decreased ability of the organism to maintain the homeostatic balance (1,7,31,42–45).

It is generally accepted that the activities and capacities of antioxidant systems decline with age, leading to the gradual loss of pro-oxidant/antioxidant balance and accumulation of oxidative damage in the aging process. Although many researchers have studied the age-related changes in antioxidant defenses, still the results are controversial (46). The rate of accumulation of free radical DNA damage reflects the relationship between the rates of its formation and repair (31). Hence, many defense mechanisms within the organism have evolved to limit the levels of reactive oxidants and the damage they inflict (47). The concentrations of the antioxidants in normal persons vary depending on age and sex (48), and the risk of peroxide stress is compensated by the increase of certain antioxidants (1). Due to metabolic disturbances, especially with age, antioxidant levels would presumably diminish and, in the presence of an increased peroxidative stress, the lower levels of antioxidant defense systems may be inadequate for scavenging the free radicals that arise. The enzymatic antioxidant levels in the present study were shown to decline with age (Table 2) and a decline can be predicted in the ability of cells to repair the damaged DNA, hence DNA damage increased with age (31).

Tobacco smoking and several of its constituents, such as hydroquinone and catechol, have been shown to generate free radicals and induce oxidative DNA damage (21,49). Mazzetti and colleagues (50) found higher lipid peroxide levels and lower antioxidant capacity among smokers compared to nonsmokers (4). The increased free radical generation and reduced antioxidant potential form a link between cigarette smoking and oxidative stress represented by an antioxidant imbalance (Tables 3 and 4). A significant correlation of increased oxidative stress with accumulated fat (51–53) coupled with oxidant and antioxidant imbalance is an important pathogenic mechanism of obesity-associated metabolic disorders (22). BMI had a positive relationship with the oxidative stress, but antioxidant levels did not vary with BMI in the present study. Therefore, it can be opined that BMI is a significant predictor of DNA damage (54). The high risk for several chronic diseases caused by smoking and BMI is probably increased more by a low antioxidant status.

Conclusion
Antioxidant levels show a general tendency to decrease with age, which would render older people more susceptible to free radical stress and DNA damage during the biological process of aging. The study demonstrates that the strong correlates of free radicals, DNA damage, and antioxidants are cigarette smoking (7) and age, with BMI serving as a moderate predictor (may be due to the effect of dietary fat among the conditions of the Indian diet) (4). In this context, it can be suggested that attacks by oxidative stress (due to a decrease in endogenous antioxidant levels) may be altered with extracellular antioxidants (dietary antioxidants) and lifestyle changes, which may help toward the anti-aging with higher healthy longevity (1,16). Also, restriction of food (calories) delays the onset of most age-related disease, alters most physiological processes (DNA oxidation) that change with age, and extends life span (55,56). Therefore, if the age-related increase in DNA oxidation is important in aging, the increase should be retarded/reduced by dietary restriction. Finally, variations in lifestyle factors (no smoking and dietary factors toward obesity) will be of more advantage toward anti-aging.


   Acknowledgments
Top
 Abstract
 Method
 Results
 Discussion
 References
 
We thank the Indian Council of Medical Research (New Delhi) and the Anthropological Survey of India (Kolkata) for the grant support in completing this research successfully.


   Footnotes
Top
 Abstract
 Method
 Results
 Discussion
 References
 
Decision Editor: Huber R. Warner, PhD

Received July 11, 2007

Accepted October 24, 2007


   References
Top
 Abstract
 Method
 Results
 Discussion
 References
 

  1. Hamilton ML, Holly VR, Jessica AD, et al. Does oxidative damage to DNA increase with age? Proc Natl Acad Sci U S A. 2000;98:10469-10474.
  2. Stadtman ER. Protein oxidation and Aging. Science. 1992;257:1220-1224.[Abstract/Free Full Text]
  3. Packer L. Vitamin E, physical exercise and tissue damage in animals. Med Biol. 1984;62:105-109.[Medline]
  4. Reddy KK, Ramamurthy R, Somasekaraiah BV, Kumara Reddy TP, Papa R. A free radicals and antioxidants status in urban and rural Tirupati men: interaction with nutrient intake, substance abuse, obesity and body fat distribution. Asia Pacific J Clin Nutr. 1997;6:296-311.
  5. Kumaran S, Kavin SP. Oxidative stress and DNA single strand breaks in skeletal muscle of aged rats: role of carnitine and lipoicacid. Biogerontology. 2006;7:111-118.[Medline]
  6. Salganik RI, Solovyova NA, Dikalov SI, Grishaeva ON, Semenova LA, Popovsky AV. Inherited enhancement hydroxyl generation and lipid peroxidation in the S strain rats results in DNA rearrangements, degenerative diseases, and premature aging. Biochem Biophys Res Commun. 1994;199:726-733.[Medline]
  7. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90:7915-7922.[Abstract/Free Full Text]
  8. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998;78:547-581.[Abstract/Free Full Text]
  9. Wallace DC. Mitochondrial genetics: a paradigm for aging and degenerative diseases. Science. 1992;256:628-632.[Abstract/Free Full Text]
  10. Sohal RS, Dube A. Mitochondrial oxidative damage, hydrogen peroxide release, and aging. Free Radic Biol Med. 1994;16:621-626.[Medline]
  11. Stadtman ER, Oliver CN. Metal catalysed oxidation of proteins. J Biol Chem. 1991;266:2005-2008.[Free Full Text]
  12. Reddy KK, Ramachandraiah T, Soorya Kumari K, Reddanna P, Thyagaraju K. Serum lipid peroxides and antioxidant defense components of rural and urban populations and aging. Age. 1993;16:9-14.
  13. Hirai S, Okamoto K, Mormatsu M. Lipid Peroxidase in Biology and Medicine. Yagi K, ed. New York: Academic Press; 1982.
  14. Mehlhorn RJ, Cole G. The free radical theory of aging: a critical review. Adv Free Radic Biol Med. 1985;1:165-223.
  15. Sies H. Strategies of antioxidant defense. Eur J Biochem. 1993;215:213-219.[Medline]
  16. Reddy KK, Papa Rao A, Reddy TPK. Serum vitamins E, A and lipid peroxidation levels in Kurichias: an Indian tribal population. Ind J Biochem Biophysics. 1999;36:44-50.
  17. Redon J, Oliva MR, Tormos C, et al. Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension. 2003;41:1096-1101.[Abstract/Free Full Text]
  18. Reddy KK, Ramachandraiah T, Reddanna P, Thyagaraju K. Serum lipid peroxides and lipids in urban and rural Indian men. Arch Environ Health. 1994;49:123-127.[Medline]
  19. Reddy KK, Reddy TPK, Somasekharaiah BV, Soorya Kumari K. Free radical generation and lipid peroxidation among the dry cell industry workers exposed to carbon. Ind J Clin Biochem. 1998;13:27-32.
  20. Olliver JR, Hardie LJ, Gong YY, et al. Risk factors, DNA damage, and disease progression of Barrett's esophagus. Cancer Epidemiol Biomarkers Prev. 2005;14:620-625.[Abstract/Free Full Text]
  21. Peto R, López A, Boreham J, Thun M, Heath C. Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet. 1992;339:1268-1278.[Medline]
  22. Beltowski J, Wojcicka G, Gorny D, Marciniak A. The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. J Physiol Pharmacol. 2000;51:883-896.[Medline]
  23. Demirbag R, Yilmaz R, Kocygit A. Relationship between DNA damage, total antioxidant capacity and coronary heart disease. Mutat Res Fundam Mol Mech Mutagen. 2005;570:197-203.
  24. Hoar DI. Molecular diagnosis: new horizons in medicine. Can Fam Physician. 1987;33:401-404.
  25. Das UN, Begin ME, Ells G, Huang YS, Horrobin DF. Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro. Biochem Biophys Res Commun. 1987;145:15-21.[Medline]
  26. Pick E, Kelsari Y. A simple colorimetric method for the measurement of H2O2 produced by cells in culture. J Immunol Methods. 1980;38:61-70.
  27. Habig WH, Pabst MJ, Jacoby WB. Glutathione S-transferase. First enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130-7139.[Abstract/Free Full Text]
  28. Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247:3170-3175.[Abstract/Free Full Text]
  29. Beer RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952;195:133-140.[Free Full Text]
  30. Langfinger D, Von Sonntag C. {gamma}-radiolysis of 2-deoxyguanosine. The structure of the malondialdehyde like product. Z Naturforch C Biosci. 1985;40C:446-448.
  31. Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN. Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci U S A. 1990;87:4533-4537.[Abstract/Free Full Text]
  32. Kaneko T, Tahara S, Matsuo M. Non-linear accumulation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidized DNA damage, during aging. Mutat Res. 1996;316:277-285.[Medline]
  33. Chung MH, Kasai H, Nishimura S, Yu BP. Protection of DNA damage by dietary restriction. Free Radic Biol Med. 1992;12:523-525.[Medline]
  34. Anson RM, Senturker S, Dizdaroglu M, Bohr VA. Measurement of oxidatively induced base lesions in liver from Wistar rats of different ages. Free Radic Biol Med. 1999;27:456-462.[Medline]
  35. Holliday R. The inheritance of epigenetics disease. Science. 1987;238:163-170.[Abstract/Free Full Text]
  36. Kirkwood TBL. DNA, mutations and aging. Mutat Res. 1989;219:1-7.[Medline]
  37. Sharma R. Physiological Basis of Geriatrics. Timiras PS, ed. New York: Macmillan; 1988.
  38. Ames BN. Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun. 1989;7:121-128.[Medline]
  39. Loeb LA. Endogenous carcinogenesis: molecular oncology into the twenty-first century—presidential address. Cancer Res. 1989;49:5489-5496.[Free Full Text]
  40. Harman D. The aging process. Proc Natl Acad Sci U S A. 1981;78:7124-7128.[Abstract/Free Full Text]
  41. Zahn RK, Jaud S, Schroder HC, Zahn-Daimler G. DNA status in brain and heart as prominent co-determinant for life span? Assessing the different degrees of DNA damage, damage susceptibility, and repair capability in different organs of young and old mice. Mech Aging Dev. 1996;89:79-94.[Medline]
  42. Ames BN, Gold LS. Endogenous mutagens and the causes of aging and cancer. Mutat Res. 1991;250:3-16.[Medline]
  43. Guo ZM, Hedari AR, Richardson A. Nucleotide excision repair of actively transcribed versus non-transcribed DNA in rat hepatocytes: effect of age and dietary restriction. Exp Cell Res. 1998;245:228-238.[Medline]
  44. Hudson EK, Hogue BA, Souza-Pinto NC, et al. Age associated change in mitochondrial DNA. Free Radic Res. 1998;29:573-579.[Medline]
  45. Goukassian D, Gad F, Yaar M, Eller MS, Nehal US, Gilchrest BA. Mechanisms and implications of age-associated decrease in DNA repair capacity. FASEB J. 2000;14:1325-1334.[Abstract/Free Full Text]
  46. Rikans LE, Hornbrook KR. Lipid peroxidation, antioxidant protection and aging. Biochim Biophys Acta. 1997;1362:116-127.[Medline]
  47. Sies H, Stahl W, Sundquist AR. Antioxidant functions of vitamins: vitamin E & C, beta-carotene, and other carotenoids. Ann N Y Acad Sci. 1992;669:7-20.[Medline]
  48. Olinescu R, Radaceanu V, Nia S, Lupeanu E. Age dependent variations of the plasma peroxides and total antioxidants in women with obesity and hypothyroidism. Rom J Intern Med. 1992;30:285-290.[Medline]
  49. Leanderson P, Tagesson C. Cigarette smoke-induced DNA damage in cultured human lung cells: role of hydroxyl radicals and endonuclease activation. Chem Biol Interact. 1992;180:197-208.
  50. Mazzetti A, Lapenna D, Pierdomenico SD, et al. Vitamin E, C and lipid peroxidation in plasma and arterial tissue of smokers and non-smokers. Atherosclerosis. 1995;112:91-99.[Medline]
  51. Olusi SO. Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotective enzymes in humans. Int J Obes Relat Metab Disord. 2002;26:1159-1164.[Medline]
  52. Keaney JF, Larson MG, Vasan RS, et al. Obesity and systemic oxidant stress: clinical correlates of oxidative stress in the Framingham Study. Arteroscler Thromb Vasc Biol. 2003;23:434-439.[Abstract/Free Full Text]
  53. Shigetada F, Takuya F, Michio S, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752-1761.[Medline]
  54. Loft S, Fischer NA, Jeding IB, Vistisen K, Poulsen HE. 8-hydroxyguanosine as a urinary biomarker of oxidative DNA damage. J Toxicol Environ Health. 1993;40:391-404.[Medline]
  55. Sohal R, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996;273:59-67.[Abstract]
  56. Weindrech R, Walford RL. The Retardation of Aging and Disease by Dietary Restriction. Springfield, IL: Thomas; 1988.




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS