Oxidative Stress In Older Adults Research Articles

Evaluation of improvement of cognitive impairment in older adults with probiotic supplementation: A systematic review and meta-analysis

ObjectiveThis study aimed to evaluate the improvement of cognitive impairment in older adults through probiotic supplementation. MethodsA literature review on probiotic supplementation for treating cognitive impairment in older adults was conducted using English and Chinese databases from 1984 to 2023. Two researchers extracted relevant data independently, and a meta-analysis was performed with RevMan software. ResultsA comprehensive analysis of ten pertinent papers was conducted, involving a sample of 702 old adults with cognitive impairment. The findings from this study revealed that probiotic supplementation exhibited a positive impact on cognitive symptoms, specifically memory (MD = 0.14, 95% CI :0.05～0.22, P = 0.001) and overall cognitive function (SMD = 0.73, 95% CI: 0.25～1.21, P=0.003), as well as oxidative stress levels, including total antioxidant capacity (MD=52.54, 95% CI:39.52～65.56, P < 0.01), malondialdehyde (MD=−0.11, 95% CI:−0.15～−0.07, P < 0.01), and glutathione (MD=17.08, 95% CI:8.65～25.5, P < 0.01). However, probiotic supplementation failed to enhance patients' psychological symptoms (SMD =0.18, 95% CI:−0.56～0.92, P = 0.64). ConclusionsProbiotic supplementation can enhance cognitive symptoms and decrease oxidative stress in older adults with cognitive impairment. However, it does not improve psychological symptoms. More research is needed to determine the effects of probiotic supplementation on gastrointestinal symptoms and sleep quality in this population. Further supplementation and improvement will be necessary once high-quality literature becomes available.

Dose- and Intensity-Response Associations Between Leisure-Time Physical Activity and Markers of Inflammation and Oxidative Stress in Older Adults.

This study aimed to investigate the dose- and intensity-response associations between leisure-time physical activity (LTPA) and markers of inflammation and oxidative stress in older adults. Multivariable linear regression was performed to evaluate the associations among 3,559 older adults in 2015-2018 National Health and Nutrition Examination Survey. LTPA was negatively associated with inflammatory markers including C-reactive protein, segmented neutrophil count and alkaline phosphatase, and positively associated with one marker of antioxidants albumin in older adults. Compared with vigorous LTPA, moderate LTPA could provide more benefits through further decreasing white blood cell count and alkaline phosphatase, and increasing serum bilirubin and albumin. The effects of LTPA on C-reactive protein and albumin were more significant in participants with chronic diseases including diabetes, hypertension, and cancer. In conclusion, this study demonstrates the dose- and intensity-response effects of LTPA on inflammation and oxidative stress and provides exercise prescription recommendations for older adults.

Does Gotu kola supplementation improve cognitive function, inflammation, and oxidative stress more than multicomponent exercise alone? - a randomized controlled study.

A randomized control trial was conducted to investigate the synergistic effects of Gotu kola supplementation and multicomponent exercise on cognitive function, inflammation, and oxidative stress in older adults with mild cognitive impairment (MCI). Sixty participants aged 74.6±7.3 years with Mini-Mental State Examination (MMSE) scores of 20.7±2.6 were randomly assigned to one of three groups: a multicomponent exercise training group (EXE, n=20), a multicomponent exercise training with Gotu kola supplementation group (EXE+GK, n=20), or a placebo-controlled group (CON, n=20). Each participant received one capsule of placebo or 500 mg twice a day of Gotu kola extract. The multicomponent exercise program comprised of supervised resistance, aerobic, balance and dual-task training: three 80-min sessions/week for 12 weeks. The primary outcomes, such as cognitive function, inflammatory markers, and oxidative stress, were measured before and after the 12-week intervention. Following the interventions, the EXE and EXE+GK had significantly higher MMSE (P<0.01), Digit Span Forward test (DSF) (P<0.01), Digit Span Backward test (P<0.01) scores, and lower Trail Making Test parts A (P<0.01) and B (P<0.01) and lower 8-iso-prostaglandin F2α (P<0.01) and tumor necrosis factor alpha (TNF-α) (P<0.01) than the CON. The change in DSF and TNF-α in the EXE+GK had a negative correlation (r=-0.504, P<0.05). In conclusion, multicomponent exercise training with or without the supplement Gotu kola improves cognitive function, inflammation, and oxidative stress in older adults with MCI. Although supplementing with Gotu kola had no additional effects on cognitive function, it may improve the effects of multicomponent exercise on executive function by decreasing TNF-α levels.

Dietary diversity, diet quality, and oxidative stress in older adults

This cross-sectional study aimed to explore the relationship between diet quality, dietary diversity, and oxidative stress levels in older adults in parts of the Ningxia Hui Autonomous Region in northwestern China. A total of 335 participants voluntarily participated in the study from April to July 2021. Laboratory tests and questionnaires were used to obtain general characteristics, dietary conditions, and indicators of oxidative stress. The dietary diversity scores of the participants were 5.20±1.39, the diet quality indices were 56.91±11.14, and most had poor diet quality. The levels of the oxidative stress markers malondialdehyde, superoxide dismutase, 8-iso-prostaglandin F2α, and total antioxidant capacity were 4.77±1.77, 40.33±9.85, 763.10±245.41, and 1.02±0.14, respectively. The results showed that the diet quality scores of participants were related to dietary diversity and whether the scores passed or not was significantly related to total antioxidant capacity.

Sarcopenia in the elderly versus microcirculation, inflammation status, and oxidative stress: A cross-sectional study

Age-related mechanisms of sarcopenia associated with vascular function have been recently suggested. This study compared and tested associations between muscle mass and strength, microcirculation, inflammatory biomarkers, and oxidative stress in older adults classified as sarcopenic and non-sarcopenic. Thirty-three physically inactive individuals (72±7 yrs) were assigned to age-matched sarcopenic (SG) and non-sarcopenic (NSG) groups. Between-group comparisons were performed for appendicular skeletal mass (ASM), handgrip and isokinetic strength, microvascular function and morphology, C-reactive protein, insulin-like growth factor-1, tumor necrosis factor-alpha, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, endothelin-1, and oxidized low-density lipoprotein. ASM and knee isokinetic strength were lower in SG than NSG (P < 0.05). No difference between groups was found for outcomes of microvascular function and morphology, but log-transformed IL-6 concentration was twice greater in SG vs. NSG (P = 0.02). Correlations between ASM index, handgrip and knee isokinetic strength vs. markers of microcirculatory function, capillary diameters, vascular reactivity, and endothelial injury were found only in SG. Decreased ASM index and strength have been associated with microcirculatory profile, indicating that microcirculation impairment may be involved somehow in Sarcopenia development. The inflammation status, particularly elevated IL-6, seems to play an important role in this process.

Inflammatory and oxidative stress responses of healthy elders to solar-assisted large-scale cleaning system (SALSCS) and changes in ambient air pollution: A quasi-interventional study in Xi'an, China

An outdoor solar assisted large-scale cleaning system (SALSCS) was constructed to mitigate the levels of fine particulate matter (PM2.5) in urban areas of Xi'an China, providing a quasi-experimental opportunity to examine the biologic responses to the changes in pollution level. We conducted this outdoor SALSCS based real-world quasi-interventional study to examine the associations of the SALSCS intervention and changes in air pollution levels with the biomarkers of systemic inflammation and oxidative stress in healthy elders. We measured the levels of 8-hydrox-2-deoxyguanosine (8-OHdG), Interlukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α) from urine samples, and IL-6 from saliva samples of 123 healthy retired participants from interventional/control residential areas in two sampling campaigns. We collected daily 24-h PM2.5 samples in two residential areas during the study periods using mini-volume samplers. Data on PM10, gaseous pollutants and weather factors were collected from the nearest national air quality monitoring stations. We used linear mixed-effect models to examine the percent change in each biomarker associated with the SALSCS intervention and air pollution levels, after adjusting for time trend, seasonality, weather factors and personal characteristics. Results showed that the SALSCS intervention was significantly associated with decreases in the geometric mean of biomarkers by 47.6% (95% confidence interval: 16.5–67.2%) for 8-OHdG, 66% (31.0–83.3%) for TNF-α, 41.7% (0.2–65.9%) and 43.4% (13.6–62.9%) for urinary and salivary IL-6, respectively. An inter-quartile range increase of ambient PM2.5 exposure averaged on the day of the collection of bio-samples and the day before (34.1 μg/m3) was associated, albeit non-significantly so, with 22.8%–37.9% increases in the geometric mean of these biomarkers. This study demonstrated that the SALSCS intervention and decreased ambient air pollution exposure results in lower burden of systemic inflammation and oxidative stress in older adults.

Circulating microRNAs and Molecular Oxidative Stress in Older Adults with Neuroprogression Disorders.

Background circulating microRNAs are potential blood biomarkers differentially expressed in many diseases including neuro depression disorders. It controls the expression of human genes and associated cellular and physiological processes in normal and diseased cells. We aimed to evaluate the potential role of circulating miRNAs and their association with both stress hormones and cellular oxidative stress in neuro depression disorders occurred among older adults. Methods a total of 70 healthy subjects were included in this study. Based upon the profile of mood states (POMS-32 score), the participants classified into two groups; healthy subjects (n =30) and depression (n =40). The expression of microRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a and their correlation with cellular oxidative stress parameters; cellular NO, genes of SOD2, CAT and iNOS, and hormones; cortisol and serotonin were estimated by a quantitative real-time RT-PCR, high-performance liquid chromatography, and ELISA Immunoassay techniques, respectively. Results depression was reported in 57.14% of the participants. The results showed a significant increase (p =0.01) in the total mood scores, and relative depression domains in older adults with depression compared to healthy controls. The relative expression levels of miR-124, miR-34a-5p significantly increased and the expression levels of miR-135, and miR-451-a significantly decreased in older adults with depression compared to healthy controls. In addition, the levels of cortisol significantly increased and serotonin (5HT) significantly reduced in all participants with depression. Cellular oxidative stress analysis for depressed subjects showed that serum NO levels and the expression of iNO gene significantly increased conversely with a decline in the molecular expression antioxidative genes; SOD2, CAT, respectively. The results showed that cellular oxidative stress parameters correlated positively with depression scores, cortisol, and negatively with cellular serotonin levels. In depressed subjects, the relative expression of microRNAs correlated positively with depression score, NO, iNOS, cortisol, and negatively associated with SOD2, CAT, and serotonin. Conclusion The combination of cellular oxidative stress and hormonal levels strongly supports a role for circulating miRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a in the regulation of depression and mood disorders among older adults. The expressed microRNAs with their related association to cellular oxidative stress and adrenal hormones are a step towards understanding the role of these small RNA molecules in the progression of depression among older adults. Thus, cellular miRNAs might have a prognostic role in the diagnosis and as a target for treatment strategies in depressed subjects.

The Effects of Aerobic Exercise on Oxidative Stress in Older Adults: A Systematic Review and Meta-Analysis.

Background: Oxidative stress (OS) plays an important role in the progression of many aging-related diseases. Exercises can delay this kind of progress, but aerobic exercise is the most commonly used type of training among older adults; therefore, its influence needs to be further verified. Methods: A literature search was conducted in eight electronic databases, including Cochrane, EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Date, and SinoMed from their inception to April 2020. Methodological quality was assessed using Cochrane RoB tool v2.0 for individual studies, and RevMan 5.3 software was used to perform the meta-analysis. Results: The meta-analysis included 20 studies, involving 1,170 older adults. The results showed that regular aerobic exercise could reduce blood oxidant markers, including malondialdehyde (MDA; SMD=−1.80, 95% CI −2.46 to −1.14, p<0.001) and lipid peroxide (LPO; SMD=−1.12, 95% CI −2.03 to −0.22, p=0.02), and increase the levels of antioxidant factors, such as nitric oxide (NO; SMD=0.89, 95% CI 0.37–1.41, p<0.001), superoxide dismutase (SOD; SMD=0.63, 95% CI 0.25–1.01, p=0.001), and total antioxidant capacity (TAC; SMD=1.22, 95% CI 0.45–1.98, p=0.002), with clear statistical significance. It may also improve the levels of other OS markers, such as 8-OHdG, 8-isoPGF2, VE, and reduced glutathione/oxidized glutathione (GSH/GSSG). Conclusion: Regular aerobic exercise may have a positive effect on the OS levels of older adults by reducing some oxidant markers and increasing antioxidant marker levels.

Obesity and Oxidative Stress in Older Adults At Risk for Dementia: A Magnetic Resonance Spectroscopy Study.

This study aimed to investigate the relationship between obesity and oxidative stress in older adults at risk for dementia. It also aimed to explore the influence of physical activity on the relationship between obesity and oxidative stress in this at risk cohort. Older adults at risk for dementia underwent comprehensive medical, neuropsychological, and psychiatric assessment. At risk was defined as participants with subjective or mild cognitive impairment. Glutathione was assessed by magnetic resonance spectroscopy in the left hippocampus and the anterior and posterior cingulate cortex. Body mass index (BMI) was calculated and classified as healthy (BMI <25 kg/m2) or overweight/obese (BMI ≥25 kg/m2). Sixty-five older adults (mean age=66.2 y) were included for analysis. The overweight/obese group had significantly greater glutathione in the hippocampus compared with the healthy weight group (t=-2.76, P=0.008). No significant difference in glutathione was observed between groups in the anterior or posterior cingulate. In the overweight/obese group, a higher BMI was associated with a diabetes diagnosis and lower total time engaging in physical activity (r=-0.36, P=0.025), however, glutathione did not correlate with activity levels across groups. This study demonstrates that changes in in vivo markers of oxidative stress are present in overweight/obese older adults at risk for dementia. Future research should explore the relationship with diabetes and the longitudinal relationship between BMI and oxidative stress, and response to therapeutic interventions.

Reversing Cognitive Decline in Aging: Reversible Mechanistic Defects and a Novel Nutritional Intervention

Aging is the biggest risk factor for cognitive-decline and Alzheimer’s disease (AD), but underlying mechanisms are not well-understood and interventions are lacking. Cognitive-decline in AD has been associated with deficiency of glutathione, (the most abundant, intracellular, antioxidant protein), elevated oxidative-stress, insulin-resistance and increased inflammation. We identified and reported that glutathione-deficiency and oxidative-stress in older-adults occur due to decreased availability of precursor amino-acids glycine and cysteine, and can be corrected with GlyNAC (a combination of glycine and the cysteine precursor N-acetylcysteine). We hypothesized that cognitive decline in older-adults is linked to glutathione-deficiency, mitochondrial-dysfunction, oxidative-stress, insulin-resistance, and inflammation. The first abstract discusses the rationale and findings of an open-label clinical trial: compared to young-humans, older-adults had cognitive-decline, glutathione-deficiency, mitochondrial-dysfunction, abnormal glucose-metabolism and insulin-resistance, oxidative-stress, endothelial-dysfunction and inflammation. These defects were improved/reversed by supplementing GlyNAC for 24-weeks, but benefits receded on stopping GlyNAC for 12-weeks. The second abstract presents a study in 8 young (20-weeks old) and 16 aged (90-weeks old) wild-type male C57BL/6J mice where we found that aged-mice had naturally-occurring cognitive-impairment, and brain defects in glutathione-deficiency, oxidative-stress, glucose-transport, mitochondrial glucose-oxidation, insulin-resistance, endoplasmic-reticulum stress, autophagy, mitophagy, inflammation, senescence, genomic and telomere damage. Aged-mice received either GlyNAC or isonitrogenous-placebo supplementation for 8-weeks, and only GlyNAC-fed mice improved cognition and brain defects. Collectively these data highlights the discovery of novel and reversible mechanistic defects in older-adults and aged-mice with naturally-occurring cognitive-decline, and identifies that supplementing GlyNAC can improve brain-health and cognition. These findings could have important implications for reversing cognitive-decline in older-adults, and AD.

Longitudinal Associations of Body Mass Index, Waist Circumference, and Waist-to-Hip Ratio with Biomarkers of Oxidative Stress in Older Adults: Results of a Large Cohort Study

Background: In the literature, obesity is discussed as a determinant of high oxidative stress (OS). Hence, prevention or reduction of obesity could prevent high OS and subsequently serve as a target for “healthy aging.” Methods: Diacron’s reactive oxygen metabolites test (D-ROM) and total thiol levels (TTL), a marker of antioxidant defense capacity, were measured in 1,734 participants of a population-based cohort study of older adults (age range: 57–83 years) at 2 time points 3 years apart. The longitudinal associations of body mass index, waist-to-hip ratio, and waist circumference with D-ROM and TTL were assessed with multivariable adjusted generalized linear models. Dose-response analyses were conducted with restricted cubic splines. Results: D-ROM was not significantly associated with any of the weight measures. On the contrary, TTL showed statistically significant, inverse linear associations with all weight measures. Conclusion: A healthy body weight seems to be highly relevant for the antioxidative defense capacity of human beings. In contrast, D-ROM levels were independent of the study participant’s weight. Clinical trials are needed to corroborate if loss of weight by obese individuals can effectively increase TTL and subsequently also life expectancy.

Effects of Tart Cherry Juice on Biomarkers of Inflammation and Oxidative Stress in Older Adults.

Inflammation and oxidative stress are important factors in the development of cardiovascular disease and atherosclerosis. The findings of our previous study suggest that 12 weeks consumption of tart cherry juice lowers the levels of systolic blood pressure (BP) and low-density lipoprotein (LDL) cholesterol in older adults. The present study investigated the effects of tart cherry juice on blood biomarkers of inflammation and oxidative stress. In this randomized-controlled clinical trial, a total of 37 men and women between the ages of 65–80 were randomly assigned to consume 480 mL of tart cherry juice or control drink daily for 12 weeks. Several blood biomarkers of inflammation and oxidative stress were assessed at baseline and after 12 weeks intervention. After the 12 weeks intervention, tart cherry juice significantly increased the plasma levels of DNA repair activity of 8-oxoguanine glycosylase (p < 0.0001) and lowered (p = 0.03) the mean c-reactive protein (CRP) level compared to the control group. There was a significant group effect observed for plasma CRP (p = 0.03) and malondialdehyde (MDA) (p = 0.03), and a borderline significant group effect observed for plasma oxidized low-density lipoprotein (OxLDL) (p = 0.07). Within group analysis showed that the plasma levels of CRP, MDA, and OxLDL decreased numerically by 25%, 3%, and 11%, respectively after 12 weeks of tart cherry juice consumption compared with corresponding baseline values. The present study suggests that the ability of tart cherry juice to reduce systolic BP and LDL cholesterol, in part, may be due to its anti-oxidative and anti-inflammatory properties. Larger and longer follow-up studies are needed to confirm these findings.

Effects Of Long-term Elastic Resistance Training On Oxidative Damage Of DNA In Older Adults

It is theorized that age-related physiological changes are a consequence of the accumulation of random oxidative damage to deoxyribonucleic acid (DNA), lipids, and proteins. The major by-product of oxidative DNA damage, 8-Oxo-7,8-dihydro-2’-deoxyguanosine (8-oxo-dG), is the most extensively analyzed oxidative stress marker. The concentration of this biomarker increases as age increases. A higher concentration of 8-oxo-dG is related to diseases such as Alzheimer’s, osteoporosis and oncogenesis. Despite the multiple benefits of resistance training on the aging process, the effect upon mitochondrial function and oxidative stress in older adults is unknown. PURPOSE: To determine the effects of a long-term, moderate-intensity elastic resistance training (ERT) program on oxidative damage of DNA in older adults. METHODS: 46 sedentary older adults (69.1 ± 5.1 yr) were randomized into two groups: Control Group (CG) (n=15) and ERT group (ERTG) (n=31). A 32-wk ERT program was performed 2d/wk with 6 exercises (3 for upper and 3 for lower extremities) completed for 4 sets of 15 repetitions. Perceived effort was 6-7 on the OMNI-RES scale for elastic bands during the first 4 wks and at 8-9 for the final 28 wks. Urine 8-oxo-dG was analyzed using high-performance liquid chromatography at baseline, 16 and 32 wks. Urinary levels of 8-oxo-dG were calculated relative to creatinine levels. Trial (3) by group (2) repeated measures ANOVA was used to determine differences. RESULTS: 8-oxo-dG was not different between groups at baseline (CG: 3.20 ± 2.51; ERTG: 3.72 ± 2.47 nmol/nmol creatinine). ERTG showed a significant (p<0.05) decrease in 8-oxo-dG for time and group of 26.07% at 16 wks and 49.43% at 32 wks. CONCLUSION: It is possible to reduce oxidative damage of DNA in older adults through regular ERT performed at moderate intensity. A longer training duration provokes greater effects on oxidative stress metabolism. These results highlight the possibility of using a non-invasive and low cost diagnostic method in conjunction with a simple and inexpensive ERT to prevent oxidative stress in older adults.

Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease

ObjectivesThe aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear. MethodsSeventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b–G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo. ResultsDuring T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD). ConclusionIn older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass.

Systemic oxidative stress in older adults: Do peripheral blood mononuclear cells contribute?

Although it is well known that systemic oxidative stress increases with age, the sources and mechanisms contributing to aging induced increase in oxidative stress remain unclear. Recent findings in animals indicate that peripheral blood mononuclear cells (PBMCs) are a major source of systemic oxidative stress via stimulation of the angiotensin II type 1 receptor (AT1R)‐NADPH oxidase pathway. Thus, to better understand this pathway and its potential contribution to increased oxidative stress with age, PBMCs were isolated from whole blood in healthy recreationally active older (61 ± 2 years, n=5) and younger men (25 ± 2 years, n=7). Intracellular superoxide production was measured using dihydroethidium fluorescence and NADPH oxidase subunits (gp91phox, p22phox, and p67phox) and superoxide dismutase 1 and 2 (SOD1 and SOD2) mRNA expression was measured using real time RT‐PCR. Interestingly, intracellular superoxide production was similar between groups (2 ± 0.4 older vs. 2 ± 0.3 young, Relative Fluorescence Units; P&gt;;0.05). Likewise, gp91phox and p22phox were not different between groups, whereas p67phox was actually significantly lower in older subjects. Aging did not influence SOD2 mRNA expression, while SOD1 expression was lower in older subjects. These preliminary findings suggest that PBMCs may not be a primary source of systemic oxidative stress in healthy older individuals.Supported by NIH Grant R01 HL093167

Exercise and nutritional interventions for improving aging muscle health

Skeletal muscle mass declines with age (i.e., sarcopenia) resulting in muscle weakness and functional limitations. Sarcopenia has been associated with physiological changes in muscle morphology, protein and hormonal kinetics, insulin resistance, inflammation, and oxidative stress. The purpose of this review is to highlight how exercise and nutritional intervention strategies may benefit aging muscle. It is well known that resistance exercise training increases muscle strength and size and evidence also suggests that resistance training can increase mitochondrial content and decrease oxidative stress in older adults. Recent findings suggest that fast-velocity resistance exercise may be an effective intervention for older adults to enhance muscle power and functional capacity. Aerobic exercise training may also benefit aging skeletal muscle by enhancing mitochondrial bioenergetics, improving insulin sensitivity, and/or decreasing oxidative stress. In addition to exercise, creatine monohydrate, milk-based proteins, and essential fatty acids all have biological effects which could enhance some of the physiological adaptations from exercise training in older adults. Additional research is needed to determine whether skeletal muscle adaptations to increased activity in older adults are further enhanced with effective nutritional interventions and whether this is due to enhanced muscle protein synthesis, improved mitochondrial function, and/or a reduced inflammatory response.

Oxidative stress in older adults: effects of physical fitness

Acute exercise results in transient change in redox balance. High concentrations of reactive oxygen species (ROS) can lead to oxidative damage to macromolecules. However, moderate periodic increases in ROS, such as experienced with habitual exercise, may activate signal transduction pathways which stimulate increases in endogenous antioxidant systems. This study tested the hypothesis that physically fit older adults would have less oxidative stress than unfit age-matched controls, due to greater circulating concentrations of non-enzymatic antioxidants and greater capacity to upregulate antioxidant enzymes. We compared 37 fit (mean age 65.2 ± 5years) and 35 unfit (mean age 67.7 ± 4years) men and women. Fitness status was classified by VO(2max) and maximal leg power. Basal levels of oxidative stress were assessed by measuring urinary markers of nucleic acid damage and lipid peroxidation. Antioxidant status was assessed by measuring total antioxidant power and ratios of reduced to oxidized glutathione in plasma, at rest. The capacity to counteract an oxidative insult was assessed by measuring changes in plasma F(2)-isoprostanes in response to forearm ischemia-reperfusion. The fit individuals had significantly lower levels of urinary markers of oxidative damage (all P <0.05) and lower F(2)-isoprostane response to the oxidative challenge (P < 0.05), but there were no group differences in antioxidant status. The lower levels of oxidative stress in the fit individuals were not mediated by known effects of exercise training such as adiposity, HDL concentrations, or small molecular weight antioxidants. These data suggest that reduced oxidative stress associated with physical fitness results from differences in activity of antioxidant enzymes.

A moderate intensity exercise program did not increase the oxidative stress in older adults

Oxidative damage to lipoproteins, in particular low density lipoprotein (LDL), is known to play a role in a number of diseases associated with aging such as cardiovascular disease (CVD) and dementia. Exercise can alter the balance of oxidative and anti-oxidative species within the human body and may cause oxidative damage to lipoproteins. The purpose of this study was to assess the effect of a moderate intensity exercise program on markers of oxidative stress in older age adults. Parameters of lipoprotein protein and lipid oxidation, and lipoprotein nitration were assessed in aged individuals who undertook a program of moderate physical activity for a period of 8 weeks. There were no significant changes in LDL protein oxidation or nitration which could be attributed to 8 weeks of walking exercise, however, LDL nitration was increased following acute steady state exercise (pre-: 0.34±0.1 vs. post-: 0.44±0.07μm/mg LDL; p=0.04). Walking at moderate intensity caused a significant weight decrease in the exercise group, but did not have any significant effect on VO2max. Exercise at this intensity was not harmful and did not increase risk factors for diseases associated with oxidative stress in the participants of the study.

Oxidative Stress in Older Adults: Effects of Fitness and Lifetime Physical Activity

We previously demonstrated an age-related decline in the ability to constrain oxidative stress induced by forearm ischemia-reperfusion (I/R) and that this response could be improved with a dietary antioxidant intervention. Reactive oxygen species (ROS) at low concentrations are important in cell signaling with one important effect being upregulation of endogenous antioxidant enzymes. Therefore, repeated bouts of transient ROS production induced by acute exercise may also increase the ability to constrain oxidative stress and reduce oxidative damage. PURPOSE: This cross-sectional study tested the hypothesis that physical fitness and/or lifetime physical activity modulate the capacity to constrain acute oxidative stress and basal urinary excretion of oxidative damage products in healthy older men and women. METHODS: We compared 40 fit and 39 unfit men and women, ages 60-78y (mean age: 66 ± 5y). Fitness status was classified by measuring VO2 max and maximal leg power, using age- and gender appropriate norms. Lifetime physical activity (low, moderate, high) was assessed with the Historical Leisure Physical Activity (HLPA) questionnaire. The capacity to constrain oxidative stress was measured as plasma F2-isoprostane (F2isoP) responses to forearm I/R. Basal systemic levels of oxidative damage were assessed by measuring urinary excretion products of lipid and nucleic acid oxidation. RESULTS: VO2max, maximal leg power, and HLPA score were significantly different between groups (p<0.001). F2isoP levels were significantly increased in response to the I/R trial (p<0.001). Fit individuals who reported high lifetime physical activity had significantly lower I/R-induced F2isoP response compared to unfit individuals who reported low lifetime physical activity (p<0.05). Compared to the unfit, sedentary group, the fit active group also had significantly lower levels of urinary markers of oxidative damage (8-OHdG, 8-oxo-G; p<0.01, isoprostanes; p<0.05). CONCLUSION: These data indicate that higher physical fitness levels and lifetime physical activity of healthy older adults are associated with greater antioxidant defenses and lower oxidative damage to lipids and nucleic acids. Furthermore, these results suggest that "quality" (VO2 max) and "quantity" (lifetime physical activity) may both be important in determining antioxidant capacity as the differences were not as marked when analyzed by either factor alone. Supported by NIH Grant R03 AG030551.

Mitochondrial DNA shifting in older adults following resistance exercise trainingThis paper article is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Aging is associated with a reduction in muscle mass and strength, which compromises functional independence. Skeletal muscle also shows an increase in mitochondrial dysfunction and oxidative stress in older adults. Resistance-exercise training is an important countermeasure for aging-associated muscle weakness. It has been shown that resistance-exercise training increases muscle strength and function in older adults, in association with a reduction in markers of oxidative stress and an improvement in mitochondrial function. Patients with sporadic mitochondrial cytopathies show an accumulation of mitochondrial DNA mutations and deletions in mature muscle, but not in satellite cells. Such patients have shown an activation of the satellite cells following myotoxic trauma and resistance, likely due to a fusion of the relatively quiescent satellite cells with mature muscle, which dilutes the mutational burden, a process called mitochondrial DNA shifting. Preliminary data strongly suggest that mitochondrial DNA shifting occurs in skeletal muscle from older adults following resistance-exercise training.