Age-related oxidative stress modulation by smoking habit and obesity

Age-related oxidative stress modulation by smoking habit and obesity

Available online at www.sciencedirect.com Clinical Biochemistry 42 (2009) 739 – 741 Age-related oxidative stress modulation by smoking habit and obe...

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Available online at www.sciencedirect.com

Clinical Biochemistry 42 (2009) 739 – 741

Age-related oxidative stress modulation by smoking habit and obesity Cristina Vassalle ⁎, Silvia Maffei, Rudina Ndreu, Antonella Mercuri G Monasterio Foundation and Institute of Clinical Physiology, CNR, Via Moruzzi 1, I-56124, Pisa, Italy Received 11 September 2008; received in revised form 29 October 2008; accepted 28 November 2008 Available online 11 December 2008

Abstract Objective: To evaluate whether obesity and smoking habit may accelerate the age-related increase of oxidative stress. Methods: The Oxidative-INDEX, a score reflecting both oxidative and antioxidant counterparts, was estimated in 179 subjects (50 males, aged 16–79 years). Results: Oxidative stress results were elevated in obese and smoker subjects. Adjusted logistic regression analysis indicated obesity and smoking as independent variables for elevated Oxidative-INDEX (odds ratio = 4.8 and 3.1, respectively). Oxidative-INDEX steadily rises at a mean rate of 5.3% (0.017 AU) per year in the overall population, showing twice and three times higher annual rate increase in smokers and obese subjects. Conclusion: Our results suggest the pro-ageing effects of cigarette smoking and obesity by a more rapid and sharp elevation of the oxidative stress status. © 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Keywords: Oxidative stress; Aging; Obesity; Body mass index; Smoking habit

Introduction The aging process is characterized by a progressive loss of functionality which in turn leads to a progressive decline in biological function and increases the susceptibility and chance of disease [1]. Although main mechanisms involved are still under discussion, due in large part to the complexity and integrative nature of this process, the oxidative stress hypothesis remains one of the prevailing theories of aging and the production of reactive oxygen species as one of the primary contributor to age-associated changes [1–2]. However, other variables from the environment may contribute to the oxidative stress status. Among them, obesity and smoking habit represent two major modifiable risk factors for many age-related diseases, both variables were found to be closely associated with elevated oxidative stress [3–4]. Nonetheless, although many data exist regarding the oxidative stress status in different physiopathological conditions, data on aging ⁎ Corresponding author. Fax: +39 050 3152166. E-mail address: [email protected] (C. Vassalle).

and oxidative stress-related increase in the presence of such lifestyle parameters are lacking. In particular, we expected a higher oxidative stress status in obese individuals and smokers, which may accelerate the increase of the oxidative stress related to advancing age. Materials and methods A total of 179 subjects were enrolled (50 males, aged 16– 79 years), all free from the presence of acute or chronic inflammatory, immunological or cardiovascular disease and history or evidence of malignancy. All participants gave detailed information about their clinical history and lifestyle habits. Height and weight were measured and body mass index (BMI) was calculated. Smoking status was coded as currently smokers, ex-smokers since at least 6 months and never smokers. None was receiving vitamin and/or antioxidant therapies, two presenting clinical Type II diabetes. Blood sample was taken after an overnight fasting status, kept on ice and centrifuged at 2500 g, 4 °C for 10 min. Then, serum samples were collected and stored at − 80 °C.

0009-9120/$ - see front matter © 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2008.11.017

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C. Vassalle et al. / Clinical Biochemistry 42 (2009) 739–741

The D-Roms and the Oxy-adsorbent test (ROM and OXY, respectively, from Diacron, Italy) were evaluated for the estimation of hydroperoxides and the total antioxidant capacity by using the automated clinical chemistry analyser SYNCHRON, CX 9 PRO (Beckman Coulter, Brea, CA, USA), as we previously described [5]. A global score of the oxidative stress status (Oxidative-INDEX), obtained by the difference between ROM and OXY standardized variables, was then calculated as we previously reported [5]. Data were expressed as the mean ± SE, unless stated. All statistical analyses were performed using the statistical package Statview, version 5.0.1 (SAS Institute, Abacus Concept, Inc., Berkeley, California) and included Student's t test, simple regression analysis, χ2 test, ANOVA analysis and Scheffe's test. A logistic regression analysis was applied to verify the effect of different variables in determining elevated OxidativeINDEX levels (N90th percentile, corresponding to a score of 1.89). A p ≤ 0.05 was considered to be statistically significant. Results Demographic characteristics of the study population are reported in Table 1. The Oxidative-INDEX steadily increased with age (r = 0.2, p b 0.05). Postmenopausal women presented higher OxidativeINDEX levels with respect to men and young women (0.45 ± 0.18 versus −0.51 ± 0.18 and − 0.025 ± 0.15, respectively, p b 0.01). Obese subjects showed higher oxidative stress status with respect to overweight and normoweight subjects (0.7 ± 0.4 versus 0.1 ± 0.17 and − 0.2 ± 0.12, respectively, p b 0.05). A significant positive correlation was also found between Oxidative-INDEX levels and values of BMI in the whole population (r = 0.2, p b 0.05). Moreover, individuals who had never smoked presented a lower oxidative stress status than former smokers and current smokers (− 0.17 ± 0.11, − 0.12 ± 0.1, 0.7 ± 0.25 AU, respectively, p b 0.01). In a model of logistic regression analysis, and after adjustment for age and gender, obesity (Odds ratio, OR = 4.8, 95% Confidence intervals, CI = 1.4–16.3, p = 0.012) and current smoking (OR = 3.1, 95% CI = 1.1–9.5, p = 0.04) were

Table 1 Demographic and clinical characteristics of studied subjects Mean ± SD Number Females Postmenopausal women Age (years) Body mass index (BMI, kg/m2) BMI ≤25 25 kg/m2 25 b BMI b 30 kg/m2 BMI ≥30 30 kg/m2 No smokers Ex smokers Current smokers OXY-Index (AU)

Range

n (%) 179 129 (72) 53 (41)

44 ± 14 25.4 ± 4.4

4 ⁎ 10− 4 ± 1.3

identified as independent variables for elevated levels of Oxidative-INDEX. In order to assess whether the oxidative stress status was increased in the presence of smoking habit or obesity with aging, the studied population was divided according to the 25th and 75th percentiles of age, corresponding to 33 and 53 years. Aging-associated oxidative stress increase resulted greater in smokers and obese subjects (p b 0.001 and p b 0.05, respectively) (Fig. 1). Moreover, when the relationship between aging and oxidative stress was examined by the regression analysis, the slope indicates that Oxidative-INDEX steadily rises at a mean rate of 5.3% (0.017 AU) per year in the overall population, and showed steeper in about twice and three times higher annual rate increase when evaluated current smoker and obese subgroups (average increase equal to 0.03 and 0.047 AU/ year, respectively). Discussion

16–79 18–42 96 (54) 64 (36) 19 (10) 137 (77) 8 (5) 34 (18) −3.8–4.9

Fig. 1. Oxidative-INDEX levels in different categories of age according to smoking habit (p b 0.001 for trend; panel A) and body mass index (BMI, p b 0.05 for trend; panel B).

Tobacco smoke is a complex mixture of chemicals including a variety of bioactive compounds and free radicals and oxidants, and it may favour aging and diseases mainly by increasing oxidative stress [4]. Accordingly, we found that Oxidative-INDEX levels progressively increase in ex- and current-smokers with respect to never-smoker subjects.

C. Vassalle et al. / Clinical Biochemistry 42 (2009) 739–741

Moreover, when biomarkers of oxidative stress were considered separately, smokers were characterized by both significantly higher hydroperoxides and a decreased total antioxidant capacity respect to the ex- and never-smokers (380 ± 23 versus 340 ± 8.8 AU, p ≤ 0.05; and 354±14 versus 402 ± 8.2 μmol/HClO, p b 0.01, respectively) (data not shown). Only a positive trend between oxidative stress levels and number of cigarettes daily smoked was also observed in smokers, although not significant (r = 0.2, p = ns, data not shown). Unfortunately, the duration of smoking habit could not be taken into account, because the precise information regarding the number of year spent smoking was not available for all smoker subjects. However, as shown in Fig. 1, the differences in the oxidative stress levels concerning smoking habit resulted particularly evident in middle-aged and elderly subjects, which had generally longer smoking habit duration. For it concerns obesity, this condition contributes to decrease life expectancy markedly [6]. Some studies have evidenced the association of overweight and obesity with enhanced levels of different indices of oxidants, and recently reviewed [3]. In our population, oxidative stress, estimated by using the OxidativeINDEX, revealed a significant positive relationship with increased BMI, while obesity represented an independent risk factor for oxidative stress. Moreover, when the index of proand anti-oxidant status was considered separately, obese subjects presented higher oxidant levels (409 ± 30 versus 340 ± 9 AU, p ≤ 0.05, data not shown). They also had reduced total antioxidant capacity (377 ± 25 versus 395 ± 8 μmol/HClO, data not shown), although levels did not reach statistical significance. A low antioxidant status has been generally found in obese subjects [3]. However, in certain stages of this condition an elevation in the antioxidant defence system to counteract oxidative stress has been observed, especially in young obese subjects [7]. Accordingly, in our obese subjects, aged between 20 and 80 years, we observed an inverse relationship between the total antioxidant status and age (r = − 0.43, p ≤ 0.05, data not shown), with total antioxidant capacity values particularly lower in elderly subjects. The relatively low number of subjects enrolled could be considered a potential limit of the study. However, the relationship with oxidative stress correlates strengthened the significance of our results. As expected, we found an increase of oxidative stress with aging, which results particularly pronounced in post-menopausal women. These results, obtained with this new integrated index of the oxidative stress status

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which included the estimation of both the pro- and anti-oxidant counterparts, are consistent with previous findings employing other oxidative stress biomarkers [1,2,8,9]. More important, a significant relationship among obesity, cigarette smoking and telomere length with age has been previously observed in a women cohort [10]. As telomeres are highly sensible to oxidative stress injuries, their length loss has been found faster in the presence of oxidative stress-related conditions, such as in the case of smoking habit or the presence of obesity [10]. Present data add evidence for this relationship providing a mechanistic basis to such previous observation, serving as the starting point to follow up this influence, possibly in intervention studies. In conclusion, present results suggest the aging-related oxidative stress increase may accelerate with lifestyle changes, such as under the effect of cigarette smoking or presence of obesity. As such, these modifiable factors can be addressed by life-style changes to potentially prevent and delay aging and correlated comorbidities maintaining a good quality of life. References [1] Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H. Trends in oxidative aging theories. Free Radic Biol Med 2007;43:477–503. [2] Junqueira VB, Barros SB, Chan SS, et al. Aging and oxidative stress. Mol Aspects Med 2004;25:5–16. [3] Vincent HK, Innes KE, Vincent KR. Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity. Diabetes Obes Metab 2007;9:813–39. [4] Morrow JD, Frei B, Longmire AW, et al. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N Engl J Med 1995;332:1198–203. [5] Vassalle C. An easy and rielable automated method to estimate oxidative stress in the clinical setting. In: Armstrong D, editor. Advanced protocols for oxidative stress in the methods in molecular biology series, 477. Humana press; 2009. Chapter 3. [6] Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA 2003;289:187–93. [7] Erdeve O, Siklar Z, Kocaturk PA, Dallar Y, Kavas GO. Antioxidant superoxide dismutase activity in obese children. Biol Trace Elem Res 2004;98:219–28. [8] Signorelli SS, Neri S, Sciacchitano S, et al. Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness. Maturitas 2001;39:39–42. [9] Vassalle C, Maffei S, Boni C, Zucchelli GC. Gender-related differences in oxidative stress levels among elderly patients with coronary artery disease. Fertil Steril 2008;89:608–13. [10] Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking, and telomere length in women. Lancet 2005;366:662–4.