- Email: [email protected]
The Pathogenesis of Dyskeratosis Congenita
60
doi: 10.1016/j.freeradbiomed.2014.10.456
Collagen and the Formation of Advanced Glycation End Products by Glyoxal and Methylglyoxal: Influence on Cell Functions Kerstin Nowotny1 and Tilman Grune1 1 German Institute of Human Nutrition, Potsdam Rehbruecke, Germany Advanced glycation end products (AGEs) are a very heterogeneous group of modified proteins and/or lipids accumulating during the aging process and in the course of several diseases such as diabetes mellitus. In addition to the activation of various cell reactions after binding on receptors of the cell surface, the pathological potential of AGEs is due to the fact that AGE formation directly leads to altered protein functions and structures. As the half-life of a protein is a crucial factor for AGE accumulation, collagen, the most frequent protein in mammals, is an abundant target for modifications. AGE formation in collagen was shown to affect matrix-matrix and matrix-cell interactions including cell adhesion, proliferation, migration and differentiation, however, different AGE precursors induced different cell reactions. After we recently established a model for AGE formation in collagen which is characterized by AGE-specific fluorescence, argpyrimidine formation and resistance to enzymatic degradation due to cross-linked molecules, we investigated in this study the influence of collagen modified with glyoxal and methylglyoxal on cell functions. Therefore, human skin fibroblasts were seeded on collagen gels and first tested for cell adhesion and proliferation. In our model, no influence on cell adhesion was observed. However, we were able to show that modified collagen affects cell growth and viability by inducing apoptosis, especially when using high concentrations of glyoxal and methylglyoxal. The mechanism of apoptosis induction is currently investigated. doi: 10.1016/j.freeradbiomed.2014.10.455
61 Exercise Training and IGF-1 Administration Increase Anabolic and Attenuate Catabolic and Apoptotic Processes in Aged Skeletal Muscle of Rats Zsolt Radak1 1 Semmelweis University, Hungary Aging results in significant loss of mass and function of skeletal muscle, which negatively impacts the quality of life. In this study we investigated whether exercise training with IGF-1 supplementation has the potential to alter anabolic and catabolic pathways in skeletal muscle. Five and twenty eight month old rats were used in the study. Aging resulted in decreased levels of follistatin/mTOR/Akt/Erk activation and increased myostatin/Murf1/2, proteasome subunits, and protein ubiquitination levels. In addition, TNF-D, reactive oxygen species (ROS), p53, and Bax levels were increased while Bcl-2 levels were decreased in skeletal muscle of aged rats. Six weeks of exercise training at 60% of VO2max and two weeks administration of IGF-1 by Alzhet pump (5 microgram/kg/day) reversed the age-associated activation of catabolic and apoptotic pathways and increased anabolic signaling. The results suggest that the age-associated loss of muscle mass and cachexia could be due to orchestrated down-regulation of anabolic and upregulation of catabolic and pro-apoptotic processes. These metabolic changes can be attenuated by exercise and IGF-1 supplementation.
S36
62 The Age-Related Decline of 20S Proteasome Adaptation to Oxidative Stress Is Dependent on SKN1 Signaling Rachel Raynes1, Crystal Juarez1, Laura C.D. Pomatto1, Derek Sieburth2, and Kelvin J.A. Davies1 1 University of Southern California, Leonard Davis School of Gerontology, USA, 2University of Southern California, Zilkha Neurogenetic Institute, Keck School of Medicine, USA Aging is marked by a collapse of protein homeostasis and deterioration of adaptive stress responses that often lead to aging-related diseases. Cellular stress response pathways are evolutionary ancient mechanisms adapted to manage the oxidized, misfolded, and damaged proteins that result from denaturing stress. Adaptation to acute stress allows cells and organisms to cope with severe stress by triggering the production of cytoprotective genes. during aging, these stress responses decline along with the proteolytic capacity of the proteasome machinery. We have recently demonstrated that induction of the proteasome upon oxidative stress is dependent on Nrf2 and that this mechanism is conserved in the C. elegans ortholog SKN-1. To our knowledge, there are currently no studies to address how the adaptive capacity to induce expression of the proteasome may change with age. We have found that the ability to mount an adaptive response by pretreatment with minor oxidative stress is abrogated in aged C. elegans. By utilizing chromatin immunoprecipitation of SKN-1, quantitative PCR to SKN-1 mRNA targets, and fluorogenic and radio-labeled substrate assays for proteolytic activity, we have found that SKN-1 signaling and adaptive proteasomal degradation of oxidized substrates decline with age. Furthermore, using a transgenic model, we have shown that constitutive activation of SKN-1 results in increased stress resistance and proteolytic activity, but is unable to restore the aging-related decline of proteasome-dependent adaptation. These results demonstrate that the aging-dependent decline in SKN-1 signaling negatively impacts adaptation of the 20S proteasome in response to oxidative stress, suggesting that rescue of SKN-1 signaling may improve protein homeostasis defects during aging. doi: 10.1016/j.freeradbiomed.2014.10.457
63 The Pathogenesis of Dyskeratosis Congenita Dara A Reeves1, Monica Bessler1,2, and Philip J Mason1 1 The Children's Hospital of Philadelphia, USA, 2University of Pennsylvania, USA Dyskeratosis Congenita (DC) is a rare inherited bone marrow failure syndrome (BMFS). DC patients typically present with nail dystrophy, leukoplakia, skin hypo- and hyperpigmentation, and are prone to BMF and cancer. DC is heterogeneous at the genetic level, with the X-linked disease being the most common. X-linked DC is caused by mutations in the DKC1 gene, encoding the protein dyskerin, which associates with the telomerase RNA (TERC) in the telomerase complex. DC pathology is generally attributed to short telomeres, due to defects in telomere maintenance that result in critically short telomeres, triggering cell senescence or apoptosis, leading to stem cell depletion and BMF. However, we pose the question of whether alternative pathways may contribute to DC pathogenesis. Previous results show that
SFRBM 2014
independent of telomere length, introduction of a pathogenic DC mutation in adult mice results in leukocytosis and a transient increase in ROS, which selectively alters the synthesis or stability of specific antioxidant enzymes. We sought to determine if our findings in mice apply to humans, and if the generation of ROS is universal in all forms of disease. We thus examined the generation of ROS in induced pluripotent stem cells (iPSCs) derived from patients with an A353V or ǻ DKC1 mutation, or TERT mutations. Preliminary results show an increase of ~1.5fold in ROS in iPSCs with an A353V mutation compared to WT cells associated with decreased SOD1 and NQO1 antioxidant expression. Correction by the addition of WT dyskerin results in a return of ROS levels to those of WT cells. In iPSCs with a double TERT mutation we observed a ~5-fold increase in ROS associated with decreased SOD1, catalase, and NQO1 DQWLR[LGDQWH[SUHVVLRQ+RZHYHUFHOOVZLWKDǻPXWDWLRQVKRZ 526OHYHOVVLPLODUWR:7FHOOVZKLOHWKHG\VNHULQFRUUHFWHGǻ lines show increased ROS generation. Interestingl\ WKH ǻ mutation is believed to inhibit the incorporation of mutant dyskerin into the telomerase complex, leading to the incorporation of mainly WT dyskerin. Therefore our results suggest a correlation between the generation of ROS and dysfunctional dyskerin via telomerase. Furthermore, our results indicate that the generation of ROS stimulates stem cells into mitosis, causing DNA damage, suggesting a possible mechanism for BMF. In recent studies, we have observed increased expression of mutant dyskerin and Ȗ+$; FRPSDUHG WR :7 G\VNHULQ LQ HLWKHU %0 RU VSOHHQ FHOOV from adult mice. Taken together our model suggests a mechanism for BMF in X-linked DC patients, and suggests oxidative stress may play a role in DC pathogenesis. doi: 10.1016/j.freeradbiomed.2014.10.458
64 Relationship between Oxidative Stress, Proinflammatory Interleukins with Periodontal Disease in Older People Raquel Retana Ugalde1, Liliana Anaya-Anaya1, Mirna Ruiz-Ramos1, and Víctor Manuel Mendoza-Nuñez1 1 Universidad Nacional Autónoma de Mexico. FES Zaragoza Unidad de Investigación en Gerontología, Mexico Background: Periodontitis is a chronic disease of the tissues supporting the teeth resulting in damage and loss of connective tissue, in this regard noted that oxidative stress (OxS) and chronic inflammation are involved in the pathogenesis of the disease. Moreover, inflammation related to aging "inflammaging" is characterized by an inflammatory process under controlled, asymptomatic chronic and systemic level which favors an increased production of proinflammatory factors such as interleukins 1 and 6, tumor necrosis factor alpha (TNF-alpha), among others. In this regard, there are no accurate reports of the association between proinflammatory interleukins oxidative stress and periodontal disease. Objective: To determine the relationship between oxidative stress proinflammatory interleukins with periodontal disease in older adults. Methods: We carried out a cross-sectional study in a sample of 75 older adults: (i) 41 clinically healthy, (ii) 34 with periodontal disease. We measured plasma lipid peroxides (LPO) by TBARS assay, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) with Randox Laboratories Kits®. The antioxidant gap (AOGAP) was calculated. A stress score (SS) ranging from 1±6, represented the severity of biomarkers modifications; a score of 1 was given to each value higher or lower than the cut-off. The IL-1, IL-6 and TNF-a was measured by ELISA, Data were analyzed by descriptive statistics,
frequencies, percentages, mean ± SD and t-test, chi-square test with a significance level of p< 0.05 using SPSS V12.0. Results: The results showed a statistically significant decrease in the total antioxidant activity in older adults with periodontitis (0.95 vs. 1.22mmol/L) as the same of AOGAP. Also we observed a statistically significant increase in concentration to interleukins 1 (6.6 vs. 51.5pg/mL) and 6 (0.8 vs. 3.2pg/mL). In relation to oxidative stress older adults with periodontal disease had a 10% OxS that healthy older adults, which is consistent with increased ERO's caused by the inflammatory process of the disease and decreased antioxidant efficiency. Conclusions: Our results suggest that older adults with periodontal disease show oxidative stress, increased concentration of proinflammatory interleukins and decreased total antioxidant activity compared to healthy older adults. This work was supported by grant DGAPA, UNAM, PAPIIT IN306213. doi: 10.1016/j.freeradbiomed.2014.10.459
65 Evidence for Obesity-Induced Acceleration of Aging Mediated by Oxidative Stress Yuhong Liu1, Yiqiang Zhang1, Vanessa Soto1, Vivian Diaz1, Kathleen Fischer2, Arlan Richardson3, and Adam Salmon1 1 University of Texas Health Science Center at San Antonio, USA, 2 University of Alabama - Birmingham, USA, 3University of Oklahoma Health Science Center, USA With a rising prevalence of REHVLW\ GHILQHGDV%0, DPRQJ all age groups in the US, there is a serious concern on the longterm effects of excess fat. Obesity dramatically increases the likelihood of mortality and the risk of several chronic illnesses such as cardiovascular disease, diabetes, and cancer leading some to suggest that this condition is representative of accelerated aging. A plausible mediator of these increased risks is the exacerbation of oxidative stress caused by obesity. In this study, we tested two fundamental questions: 1) does obesity accelerate declines in physiological function associated with aging and 2) does reducing oxidative stress reduce the risk of disease and mortality with obesity? To address these questions, we monitored C57BL/6J mice that were a fed high fat diet starting in adulthood until the end of their natural life. As predicted, we found that obesity was associated with both increased oxidative stress, altered metabolic function and increased mortality in high fat-fed mice. In addition, we also found evidence that age-related changes in activity, mobility, sleep patterns, and co-ordination were significantly worsened in high fat-fed mice even after statistical correction for increased body weight, adiposity and metabolic dysfunction. These data then suggest that the cellular mechanisms that cause these declines may be exacerbated by obesity. To identify the role of oxidative stress in these processes, we simultaneously tested whether mice with increased expression of CuZn-superoxide dismutase (Sod1 Tg) would be protected from the accelerated decline in physiological function brought on by obesity. While Sod1 Tg mice were not protected from fat accumulation due to high fat feeding, markers of oxidative damage induced by obesity in vivo caused were significantly reduced by increased Sod1. Moreover, increased Sod1 slowed some of the obesity-accelerated physiological changes with age suggesting that these processes may be driven largely by oxidative stress. In this ongoing study, longevity of high fat-fed Sod1 Tg mice is being tested to determine if reducing oxidative stress/damage is sufficient to reduce mortality in obese animals. Overall, these data suggest that lifelong obesity does accelerate some aspects of the aging process and that targeting the reduction of oxidative stress may have therapeutic potential to
SFRBM 2014
S37
doi: 10.1016/j.freeradbiomed.2014.10.456
Collagen and the Formation of Advanced Glycation End Products by Glyoxal and Methylglyoxal: Influence on Cell Functions Kerstin Nowotny1 and Tilman Grune1 1 German Institute of Human Nutrition, Potsdam Rehbruecke, Germany Advanced glycation end products (AGEs) are a very heterogeneous group of modified proteins and/or lipids accumulating during the aging process and in the course of several diseases such as diabetes mellitus. In addition to the activation of various cell reactions after binding on receptors of the cell surface, the pathological potential of AGEs is due to the fact that AGE formation directly leads to altered protein functions and structures. As the half-life of a protein is a crucial factor for AGE accumulation, collagen, the most frequent protein in mammals, is an abundant target for modifications. AGE formation in collagen was shown to affect matrix-matrix and matrix-cell interactions including cell adhesion, proliferation, migration and differentiation, however, different AGE precursors induced different cell reactions. After we recently established a model for AGE formation in collagen which is characterized by AGE-specific fluorescence, argpyrimidine formation and resistance to enzymatic degradation due to cross-linked molecules, we investigated in this study the influence of collagen modified with glyoxal and methylglyoxal on cell functions. Therefore, human skin fibroblasts were seeded on collagen gels and first tested for cell adhesion and proliferation. In our model, no influence on cell adhesion was observed. However, we were able to show that modified collagen affects cell growth and viability by inducing apoptosis, especially when using high concentrations of glyoxal and methylglyoxal. The mechanism of apoptosis induction is currently investigated. doi: 10.1016/j.freeradbiomed.2014.10.455
61 Exercise Training and IGF-1 Administration Increase Anabolic and Attenuate Catabolic and Apoptotic Processes in Aged Skeletal Muscle of Rats Zsolt Radak1 1 Semmelweis University, Hungary Aging results in significant loss of mass and function of skeletal muscle, which negatively impacts the quality of life. In this study we investigated whether exercise training with IGF-1 supplementation has the potential to alter anabolic and catabolic pathways in skeletal muscle. Five and twenty eight month old rats were used in the study. Aging resulted in decreased levels of follistatin/mTOR/Akt/Erk activation and increased myostatin/Murf1/2, proteasome subunits, and protein ubiquitination levels. In addition, TNF-D, reactive oxygen species (ROS), p53, and Bax levels were increased while Bcl-2 levels were decreased in skeletal muscle of aged rats. Six weeks of exercise training at 60% of VO2max and two weeks administration of IGF-1 by Alzhet pump (5 microgram/kg/day) reversed the age-associated activation of catabolic and apoptotic pathways and increased anabolic signaling. The results suggest that the age-associated loss of muscle mass and cachexia could be due to orchestrated down-regulation of anabolic and upregulation of catabolic and pro-apoptotic processes. These metabolic changes can be attenuated by exercise and IGF-1 supplementation.
S36
62 The Age-Related Decline of 20S Proteasome Adaptation to Oxidative Stress Is Dependent on SKN1 Signaling Rachel Raynes1, Crystal Juarez1, Laura C.D. Pomatto1, Derek Sieburth2, and Kelvin J.A. Davies1 1 University of Southern California, Leonard Davis School of Gerontology, USA, 2University of Southern California, Zilkha Neurogenetic Institute, Keck School of Medicine, USA Aging is marked by a collapse of protein homeostasis and deterioration of adaptive stress responses that often lead to aging-related diseases. Cellular stress response pathways are evolutionary ancient mechanisms adapted to manage the oxidized, misfolded, and damaged proteins that result from denaturing stress. Adaptation to acute stress allows cells and organisms to cope with severe stress by triggering the production of cytoprotective genes. during aging, these stress responses decline along with the proteolytic capacity of the proteasome machinery. We have recently demonstrated that induction of the proteasome upon oxidative stress is dependent on Nrf2 and that this mechanism is conserved in the C. elegans ortholog SKN-1. To our knowledge, there are currently no studies to address how the adaptive capacity to induce expression of the proteasome may change with age. We have found that the ability to mount an adaptive response by pretreatment with minor oxidative stress is abrogated in aged C. elegans. By utilizing chromatin immunoprecipitation of SKN-1, quantitative PCR to SKN-1 mRNA targets, and fluorogenic and radio-labeled substrate assays for proteolytic activity, we have found that SKN-1 signaling and adaptive proteasomal degradation of oxidized substrates decline with age. Furthermore, using a transgenic model, we have shown that constitutive activation of SKN-1 results in increased stress resistance and proteolytic activity, but is unable to restore the aging-related decline of proteasome-dependent adaptation. These results demonstrate that the aging-dependent decline in SKN-1 signaling negatively impacts adaptation of the 20S proteasome in response to oxidative stress, suggesting that rescue of SKN-1 signaling may improve protein homeostasis defects during aging. doi: 10.1016/j.freeradbiomed.2014.10.457
63 The Pathogenesis of Dyskeratosis Congenita Dara A Reeves1, Monica Bessler1,2, and Philip J Mason1 1 The Children's Hospital of Philadelphia, USA, 2University of Pennsylvania, USA Dyskeratosis Congenita (DC) is a rare inherited bone marrow failure syndrome (BMFS). DC patients typically present with nail dystrophy, leukoplakia, skin hypo- and hyperpigmentation, and are prone to BMF and cancer. DC is heterogeneous at the genetic level, with the X-linked disease being the most common. X-linked DC is caused by mutations in the DKC1 gene, encoding the protein dyskerin, which associates with the telomerase RNA (TERC) in the telomerase complex. DC pathology is generally attributed to short telomeres, due to defects in telomere maintenance that result in critically short telomeres, triggering cell senescence or apoptosis, leading to stem cell depletion and BMF. However, we pose the question of whether alternative pathways may contribute to DC pathogenesis. Previous results show that
SFRBM 2014
independent of telomere length, introduction of a pathogenic DC mutation in adult mice results in leukocytosis and a transient increase in ROS, which selectively alters the synthesis or stability of specific antioxidant enzymes. We sought to determine if our findings in mice apply to humans, and if the generation of ROS is universal in all forms of disease. We thus examined the generation of ROS in induced pluripotent stem cells (iPSCs) derived from patients with an A353V or ǻ DKC1 mutation, or TERT mutations. Preliminary results show an increase of ~1.5fold in ROS in iPSCs with an A353V mutation compared to WT cells associated with decreased SOD1 and NQO1 antioxidant expression. Correction by the addition of WT dyskerin results in a return of ROS levels to those of WT cells. In iPSCs with a double TERT mutation we observed a ~5-fold increase in ROS associated with decreased SOD1, catalase, and NQO1 DQWLR[LGDQWH[SUHVVLRQ+RZHYHUFHOOVZLWKDǻPXWDWLRQVKRZ 526OHYHOVVLPLODUWR:7FHOOVZKLOHWKHG\VNHULQFRUUHFWHGǻ lines show increased ROS generation. Interestingl\ WKH ǻ mutation is believed to inhibit the incorporation of mutant dyskerin into the telomerase complex, leading to the incorporation of mainly WT dyskerin. Therefore our results suggest a correlation between the generation of ROS and dysfunctional dyskerin via telomerase. Furthermore, our results indicate that the generation of ROS stimulates stem cells into mitosis, causing DNA damage, suggesting a possible mechanism for BMF. In recent studies, we have observed increased expression of mutant dyskerin and Ȗ+$; FRPSDUHG WR :7 G\VNHULQ LQ HLWKHU %0 RU VSOHHQ FHOOV from adult mice. Taken together our model suggests a mechanism for BMF in X-linked DC patients, and suggests oxidative stress may play a role in DC pathogenesis. doi: 10.1016/j.freeradbiomed.2014.10.458
64 Relationship between Oxidative Stress, Proinflammatory Interleukins with Periodontal Disease in Older People Raquel Retana Ugalde1, Liliana Anaya-Anaya1, Mirna Ruiz-Ramos1, and Víctor Manuel Mendoza-Nuñez1 1 Universidad Nacional Autónoma de Mexico. FES Zaragoza Unidad de Investigación en Gerontología, Mexico Background: Periodontitis is a chronic disease of the tissues supporting the teeth resulting in damage and loss of connective tissue, in this regard noted that oxidative stress (OxS) and chronic inflammation are involved in the pathogenesis of the disease. Moreover, inflammation related to aging "inflammaging" is characterized by an inflammatory process under controlled, asymptomatic chronic and systemic level which favors an increased production of proinflammatory factors such as interleukins 1 and 6, tumor necrosis factor alpha (TNF-alpha), among others. In this regard, there are no accurate reports of the association between proinflammatory interleukins oxidative stress and periodontal disease. Objective: To determine the relationship between oxidative stress proinflammatory interleukins with periodontal disease in older adults. Methods: We carried out a cross-sectional study in a sample of 75 older adults: (i) 41 clinically healthy, (ii) 34 with periodontal disease. We measured plasma lipid peroxides (LPO) by TBARS assay, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) with Randox Laboratories Kits®. The antioxidant gap (AOGAP) was calculated. A stress score (SS) ranging from 1±6, represented the severity of biomarkers modifications; a score of 1 was given to each value higher or lower than the cut-off. The IL-1, IL-6 and TNF-a was measured by ELISA, Data were analyzed by descriptive statistics,
frequencies, percentages, mean ± SD and t-test, chi-square test with a significance level of p< 0.05 using SPSS V12.0. Results: The results showed a statistically significant decrease in the total antioxidant activity in older adults with periodontitis (0.95 vs. 1.22mmol/L) as the same of AOGAP. Also we observed a statistically significant increase in concentration to interleukins 1 (6.6 vs. 51.5pg/mL) and 6 (0.8 vs. 3.2pg/mL). In relation to oxidative stress older adults with periodontal disease had a 10% OxS that healthy older adults, which is consistent with increased ERO's caused by the inflammatory process of the disease and decreased antioxidant efficiency. Conclusions: Our results suggest that older adults with periodontal disease show oxidative stress, increased concentration of proinflammatory interleukins and decreased total antioxidant activity compared to healthy older adults. This work was supported by grant DGAPA, UNAM, PAPIIT IN306213. doi: 10.1016/j.freeradbiomed.2014.10.459
65 Evidence for Obesity-Induced Acceleration of Aging Mediated by Oxidative Stress Yuhong Liu1, Yiqiang Zhang1, Vanessa Soto1, Vivian Diaz1, Kathleen Fischer2, Arlan Richardson3, and Adam Salmon1 1 University of Texas Health Science Center at San Antonio, USA, 2 University of Alabama - Birmingham, USA, 3University of Oklahoma Health Science Center, USA With a rising prevalence of REHVLW\ GHILQHGDV%0, DPRQJ all age groups in the US, there is a serious concern on the longterm effects of excess fat. Obesity dramatically increases the likelihood of mortality and the risk of several chronic illnesses such as cardiovascular disease, diabetes, and cancer leading some to suggest that this condition is representative of accelerated aging. A plausible mediator of these increased risks is the exacerbation of oxidative stress caused by obesity. In this study, we tested two fundamental questions: 1) does obesity accelerate declines in physiological function associated with aging and 2) does reducing oxidative stress reduce the risk of disease and mortality with obesity? To address these questions, we monitored C57BL/6J mice that were a fed high fat diet starting in adulthood until the end of their natural life. As predicted, we found that obesity was associated with both increased oxidative stress, altered metabolic function and increased mortality in high fat-fed mice. In addition, we also found evidence that age-related changes in activity, mobility, sleep patterns, and co-ordination were significantly worsened in high fat-fed mice even after statistical correction for increased body weight, adiposity and metabolic dysfunction. These data then suggest that the cellular mechanisms that cause these declines may be exacerbated by obesity. To identify the role of oxidative stress in these processes, we simultaneously tested whether mice with increased expression of CuZn-superoxide dismutase (Sod1 Tg) would be protected from the accelerated decline in physiological function brought on by obesity. While Sod1 Tg mice were not protected from fat accumulation due to high fat feeding, markers of oxidative damage induced by obesity in vivo caused were significantly reduced by increased Sod1. Moreover, increased Sod1 slowed some of the obesity-accelerated physiological changes with age suggesting that these processes may be driven largely by oxidative stress. In this ongoing study, longevity of high fat-fed Sod1 Tg mice is being tested to determine if reducing oxidative stress/damage is sufficient to reduce mortality in obese animals. Overall, these data suggest that lifelong obesity does accelerate some aspects of the aging process and that targeting the reduction of oxidative stress may have therapeutic potential to
SFRBM 2014
S37