Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of... more Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives
(p1⁄40.02) and Omega-6, LA derived 9,10-DiHOME/9,10-EpOME (p1⁄40.05.) ratios (Figures 1, 2). High... more (p1⁄40.02) and Omega-6, LA derived 9,10-DiHOME/9,10-EpOME (p1⁄40.05.) ratios (Figures 1, 2). Higher 19,20-DiHDPA/19,20-EpDPE, an omega-3 derived diol/epoxide ratio from DHA, showed a significant positive association with Trails-B (p 1⁄4 0.04) (Figure 3). There was no association with DHA or single DHA derived oxylipins or diols and Trails-B.We have previously reported a protective association with DHA P450 derived oxylipin 16,17-EpDPE and WMH (p1⁄40.005). Conclusions: MRI markers did not correlate with parent fatty acid compounds and no parent PUFA correlated with Trails-B, suggesting their derivatives may be the key mediators in brain changes. Soluble Epoxide Hydrolase-derived oxylipin products may negatively impact vascular cognitive health, therefore a better understanding of the relationships between oxylipins and diols is warranted.
Introduction: Left ventricular hypertrophy assessed by electrocardiography (ECG-LVH) is a marker ... more Introduction: Left ventricular hypertrophy assessed by electrocardiography (ECG-LVH) is a marker of subclinical cardiac damage and a strong predictor of cardiovascular events. The prevalence of ECG-LVH is increased in obesity and type 2 diabetes; thus, exercise and weight loss are recommended to lower cardiovascular disease (CVD) risk in these individuals. However, there are no data on the long term effects of diet- and/or exercise-induced weight loss on ECG-LVH. Hypothesis: We hypothesized that an intensive lifestyle intervention targeting weight loss through caloric restriction and increased physical activity reduces the incidence of ECG-LVH in overweight and obese adults with type 2 diabetes. Methods: We included 4,549 Look AHEAD participants without ECG-LVH at baseline who were randomized to a 10-year lifestyle intervention (ILI, n=2,287) or diabetes support and education (DSE, n=2,262) (mean age = 58.7±6.8 years, 64.5% White). ECG-LVH defined by the Cornell voltage criteria (Ra...
IAGG 2017 World Congress in men (coefficient=0.04, 95% CI 0.01, 0.07). Associations between high-... more IAGG 2017 World Congress in men (coefficient=0.04, 95% CI 0.01, 0.07). Associations between high-fibre bread (coef=1.05, 95% CI 0.11, 1.99), added salt (coef=-1.79, 95% CI-2.90,-0.68) and TICS-m were also observed in men. Cross-sectionally, men who consumed a diet closer to the Australian dietary guidelines, with high-fibre breads and less added salt reported better cognitive function. Future studies should investigate trajectories of dietary change over time as determinants of cognitive function in older age.
ObjectiveThis study examined the short‐ and long‐term effects of adding caloric restriction to 5 ... more ObjectiveThis study examined the short‐ and long‐term effects of adding caloric restriction to 5 months of aerobic exercise training on executive function in sedentary older adults with obesity.MethodsSedentary adults with obesity aged 65 to 79 years completed a randomized trial investigating the cardiorespiratory benefits of adding moderate (~ 250 kcal) or high (~ 600 kcal) caloric restriction to a 20‐week aerobic exercise program. Approximately half (n = 88) completed a cognitive assessment battery at baseline, post intervention, and 18 to 24 months after intervention completion. The primary outcome was an executive function composite score.ResultsIn the overall sample, the executive function composite increased 0.114 from baseline to postintervention (P = 0.01). Randomization to caloric restriction did not significantly alter executive function over aerobic exercise alone, nor were there between‐group differences on any individual executive function test following the interventio...
Background:Alzheimer’s disease (AD) is a heterogeneous complex health disorder, and the pool of A... more Background:Alzheimer’s disease (AD) is a heterogeneous complex health disorder, and the pool of AD patients is likely a mixture of cases of the different etiology, including the cases with leading genetic (e.g., APOE mutations), environmental (e.g., some toxic exposures), infectious (e.g., viruses) and mixed component. Some disease mechanisms may be more prevalent than others, and it is very important to understand relative contributions of such mechanisms to the population risk of AD, in order to develop adequate preventive strategies for this deadly disease. Accumulating evidence suggests that viral infections may potentially play pivotal role in AD development. However, exact mechanism connecting the AD and the infection, and the scope of its influence on AD risk and epidemiological trends are unclear. Methods: In this study, we estimated the risk of AD following the diagnosis of a herpesvirus, as well as the AD risk following the vaccination against herpesviruses, based on available ICD-9-CM codes, in a large sample (more than 30,000) of elderly Medicare participants aged 65+. Results:We found that being diagnosed with a herpesvirus (Herpes Simplex, Herpes Zoster or Cytomegalovirus) significantly increased the risk of AD by about 30% in both males and females aged 65+, while vaccination against these viruses did not significantly reduce the AD risk in this sample. We also found that recent time trends in AD risk resemble those reported for the shingles (Herpes Zoster). Conclusions:Results of this study support the hypothesis that AD may be linked to herpesviruses, and suggest that proportion of AD cases associated with the infection can be substantial, though not explaining most of the population risk of AD. Our results also suggest that it may be reasonable to prioritize research on the risk factors for AD that demonstrate behavior and trends consistent with the observed epidemiological trends for AD. The research was supported by the NIH grants P01AG043352 and R01AG046860.
Previous studies in obese individuals indicate higher circulating endocannabinoids anandamide (AE... more Previous studies in obese individuals indicate higher circulating endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) than in lean counterparts. However, the association between plasma endocannabinoids and autonomic control of blood pressure and heart rate has not been assessed in obesity. In a sample of normotensive, obese older adults we analyzed plasma content of the endocannabinoids AEA and total AG using mass spectrometry and examined correlations with various indices of spontaneous sympathovagal activity. Spontaneous baroreflex sensitivity (BRS) for heart rate control was calculated by spectral analysis of arterial pressure (AP) time (Sequence [Seq] Up, Seq Down and Seq All) and frequency (low-frequency [LF] and high-frequency [HF] α) domains from continuous resting AP recordings. In addition, time domain analysis was used to calculate heart rate variability (HRV) and blood pressure variability, indices of cardiac vagal tone and vascular sympathetic tone, respectively. The sample included 8 males and 17 females with a mean age of 68.4 ± 0.6 years, a mean body mass index of 35.0 ± 0.8 kg/m 2 , and mean AP of 101.0 ± 2.2 mmHg. Across the complete sample, we report a significant inverse correlation between plasma AG content and HFα, an index of the vagally-mediated parasympathetic spontaneous BRS ( r = -0.50, P < 0.05). We further report a significant inverse correlation between plasma AG and the vagal spontaneous BRS (Seq Up) in males ( r = -0.87, P < 0.01) but not in females. However, in females but not males we found significant positive relationships between AEA and LFα, an index of sympathetic spontaneous BRS ( r = 0.49, P < 0.05), and AEA and HRV ( r = 0.50, P < 0.05). These results are consistent with a role for the endocannabinoid system to modulate autonomic control of the circulation in populations at risk for hypertension and cardiovascular disease, and suggest gender differences that have yet to be elucidated.
Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovasc... more Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease. Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2295 participants (mean age: 74 years; 52% female; 40% black) from the Health, Aging, and Body Composition Study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1: 869Ϯ376 cm/s; tertile 2: 901Ϯ394 cm/s; tertile 3: 938Ϯ415 cm/s; Pϭ0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional cardiovascular disease risk factors (Pϭ0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, antihypertensive and antilipemic medications, and C-reactive protein, the association with ox-LDL was attenuated but remained significant (Pϭ0.01). Results were similar when ox-LDL was expressed in absolute (milligrams per deciliter) or relative amounts (percentage of low-density lipoprotein). Moreover, individuals in the highest ox-LDL tertile were 30% to 55% more likely to have high arterial stiffness, defined as aPWV Ͼ75th percentile (PՅ0.02). In conclusion, we found that, among elderly persons, elevated plasma ox-LDL levels were associated with higher arterial stiffness, independent of cardiovascular disease risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness. (Hypertension. 2009;53:846-852.) Key Words: aging Ⅲ epidemiology Ⅲ aortic stiffness Ⅲ pulse wave velocity Ⅲ oxidative stress A rterial stiffening, one of the most significant manifestations of vascular aging, is a complex process involving extracellular matrix proteins and smooth muscle cells. 1,2 Arterial stiffness has traditionally been linked to structural alterations in the vascular wall, including fragmentation and degeneration of elastin, increases in collagen content, arterial wall thickening, and luminal dilation. These age-related changes have adverse effects on cardiovascular health, for arterial stiffness increases systolic and pulse pressures, promotes left ventricular hypertrophy and dysfunction, and impairs coronary blood flow. 3,4 Moreover, increased arterial stiffness is associated with increased risk for cardiovascular disease (CVD) and its sequelae, including heart failure, stroke, atherosclerosis, myocardial infarction, and mortality. 1,3,5-10 Although the exact mechanisms underlying arterial stiffening are not well understood, the imbalance in oxidants and
Background-Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have bee... more Background-Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have been implicated in a number of chronic diseases. Previous studies indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However, the reasons for these differences are unclear. Purpose-We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk. Methods-Serum levels of total sRAGE, endogenous secretory RAGE (esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were measured in 99 Blacks and 454 Whites. Results-Blacks had a more adverse cardiovascular risk profile, as well as lower median levels of total sRAGE (972 vs. 1564 pg/ml) and esRAGE (474 vs. 710 pg/ml) compared to Whites (p<0.0001). In addition, the proportion of esRAGE was higher in Blacks (47% vs. 44%, p=0.02), as were the CML/total sRAGE (0.89 vs. 0.56 ng/pg) and CML/esRAGE (1.72 vs. 1.20 ng/pg)
Biologic aging reflects the genetic, molecular, and cellular changes underlying the development o... more Biologic aging reflects the genetic, molecular, and cellular changes underlying the development of morbidity and mortality with advancing chronological age. As several potential mechanisms have been identified, there is a growing interest in developing robust measures of biologic age that can better reflect the underlying biology of aging and predict age-related outcomes. To support this endeavor, the Research Centers Collaborative Network (RCCN) conducted a workshop in January 2022 to discuss emerging concepts in the field and identify opportunities to move the science forward. This paper presents workshop proceedings and summarizes the identified research needs, priorities, and recommendations for measuring biologic age. The highest priorities identified were the need for more robust measures, longitudinal studies, multidisciplinary collaborations, and translational approaches.
<p>Table values are Spearman correlation coefficients (r).</p><p>*p<0.05,<... more <p>Table values are Spearman correlation coefficients (r).</p><p>*p<0.05,</p>†<p>p≤0.0001;</p><p>Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028410#pone-0028410-t001" target="_blank">Table 1</a>.</p
BACKGROUND Experimental studies in animals suggest that circulating soluble receptor for advanced... more BACKGROUND Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end products (sRAGE) decrease oxidative stress, inflammation, and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study. METHODS We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990-1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow-up. RESULTS In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% CIs) ...
Aging affects men and women differently; however, the impact of sex and gender on the aging proce... more Aging affects men and women differently; however, the impact of sex and gender on the aging process is not well understood. Moreover, these two concepts are often conflated which further contributes to a lack of clarity on this important issue. In an effort to better understand the relevance of sex and gender in aging research, the Research Centers Collaborative Network (RCCN) sponsored a 1.5-day conference on sex and gender differences in aging that brought together key thought leaders from the six National Institute on Aging center programs. The meeting included sessions on comparing males and females, pathophysiological differences, sex/gender in clinical care, and gender and health in the social context. Presenters from a wide array of disciplines identified opportunities for multidisciplinary research to address current gaps in the field and highlighted the need for a more systematic approach to understanding the how and why of sex/gender differences, as well as the health impl...
BackgroundKetogenic diets have been used to treat both obesity and neurological disorders, includ... more BackgroundKetogenic diets have been used to treat both obesity and neurological disorders, including epilepsy and more recently Alzheimer’s disease (AD), likely due to favorable effects on both central and peripheral metabolism. Improvements in body composition have also been reported; however, it is unclear if diet-induced changes in adiposity are related to improvements in AD and related neuropathology.PurposeWe examined the effects of a Modified Mediterranean Ketogenic (MMK) diet vs. an American Heart Association (AHA) diet on body weight, body composition, and body fat distribution and their association with cerebrospinal fluid (CSF) biomarkers in older adults at risk for AD.MethodsTwenty adults (mean age: 64.3 ± 6.3 years, 35% Black, 75% female) were randomly assigned to a crossover trial starting with either the MMK or AHA diet for 6 weeks, followed by a 6-week washout and then the opposite diet for 6 weeks. At baseline and after each diet adiposity was assessed by dual-energy...
Diabetes is a potent risk factor for dementia, including Alzheimer's disease (AD) and vascula... more Diabetes is a potent risk factor for dementia, including Alzheimer's disease (AD) and vascular dementia, but the mechanisms underlying this association remain unclear. We review current evidence regarding fluid biomarkers that are associated with both AD and type 2 diabetes mellitus, as well as with closely related conditions such as prediabetes and insulin resistance. We also discuss current gaps in knowledge and methodological considerations for future studies. The identification of valid and reliable biomarkers for diabetes-related dementia that can be measured in blood products or cerebrospinal fluid can enhance our understanding of shared disease mechanisms or serve as predictors of risk, clinical progression, or treatment response. Such knowledge would provide critical insight into the basis for their association in epidemiological and population-based studies, as well as suggest strategies for treatment and prevention.
Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of... more Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives
(p1⁄40.02) and Omega-6, LA derived 9,10-DiHOME/9,10-EpOME (p1⁄40.05.) ratios (Figures 1, 2). High... more (p1⁄40.02) and Omega-6, LA derived 9,10-DiHOME/9,10-EpOME (p1⁄40.05.) ratios (Figures 1, 2). Higher 19,20-DiHDPA/19,20-EpDPE, an omega-3 derived diol/epoxide ratio from DHA, showed a significant positive association with Trails-B (p 1⁄4 0.04) (Figure 3). There was no association with DHA or single DHA derived oxylipins or diols and Trails-B.We have previously reported a protective association with DHA P450 derived oxylipin 16,17-EpDPE and WMH (p1⁄40.005). Conclusions: MRI markers did not correlate with parent fatty acid compounds and no parent PUFA correlated with Trails-B, suggesting their derivatives may be the key mediators in brain changes. Soluble Epoxide Hydrolase-derived oxylipin products may negatively impact vascular cognitive health, therefore a better understanding of the relationships between oxylipins and diols is warranted.
Introduction: Left ventricular hypertrophy assessed by electrocardiography (ECG-LVH) is a marker ... more Introduction: Left ventricular hypertrophy assessed by electrocardiography (ECG-LVH) is a marker of subclinical cardiac damage and a strong predictor of cardiovascular events. The prevalence of ECG-LVH is increased in obesity and type 2 diabetes; thus, exercise and weight loss are recommended to lower cardiovascular disease (CVD) risk in these individuals. However, there are no data on the long term effects of diet- and/or exercise-induced weight loss on ECG-LVH. Hypothesis: We hypothesized that an intensive lifestyle intervention targeting weight loss through caloric restriction and increased physical activity reduces the incidence of ECG-LVH in overweight and obese adults with type 2 diabetes. Methods: We included 4,549 Look AHEAD participants without ECG-LVH at baseline who were randomized to a 10-year lifestyle intervention (ILI, n=2,287) or diabetes support and education (DSE, n=2,262) (mean age = 58.7±6.8 years, 64.5% White). ECG-LVH defined by the Cornell voltage criteria (Ra...
IAGG 2017 World Congress in men (coefficient=0.04, 95% CI 0.01, 0.07). Associations between high-... more IAGG 2017 World Congress in men (coefficient=0.04, 95% CI 0.01, 0.07). Associations between high-fibre bread (coef=1.05, 95% CI 0.11, 1.99), added salt (coef=-1.79, 95% CI-2.90,-0.68) and TICS-m were also observed in men. Cross-sectionally, men who consumed a diet closer to the Australian dietary guidelines, with high-fibre breads and less added salt reported better cognitive function. Future studies should investigate trajectories of dietary change over time as determinants of cognitive function in older age.
ObjectiveThis study examined the short‐ and long‐term effects of adding caloric restriction to 5 ... more ObjectiveThis study examined the short‐ and long‐term effects of adding caloric restriction to 5 months of aerobic exercise training on executive function in sedentary older adults with obesity.MethodsSedentary adults with obesity aged 65 to 79 years completed a randomized trial investigating the cardiorespiratory benefits of adding moderate (~ 250 kcal) or high (~ 600 kcal) caloric restriction to a 20‐week aerobic exercise program. Approximately half (n = 88) completed a cognitive assessment battery at baseline, post intervention, and 18 to 24 months after intervention completion. The primary outcome was an executive function composite score.ResultsIn the overall sample, the executive function composite increased 0.114 from baseline to postintervention (P = 0.01). Randomization to caloric restriction did not significantly alter executive function over aerobic exercise alone, nor were there between‐group differences on any individual executive function test following the interventio...
Background:Alzheimer’s disease (AD) is a heterogeneous complex health disorder, and the pool of A... more Background:Alzheimer’s disease (AD) is a heterogeneous complex health disorder, and the pool of AD patients is likely a mixture of cases of the different etiology, including the cases with leading genetic (e.g., APOE mutations), environmental (e.g., some toxic exposures), infectious (e.g., viruses) and mixed component. Some disease mechanisms may be more prevalent than others, and it is very important to understand relative contributions of such mechanisms to the population risk of AD, in order to develop adequate preventive strategies for this deadly disease. Accumulating evidence suggests that viral infections may potentially play pivotal role in AD development. However, exact mechanism connecting the AD and the infection, and the scope of its influence on AD risk and epidemiological trends are unclear. Methods: In this study, we estimated the risk of AD following the diagnosis of a herpesvirus, as well as the AD risk following the vaccination against herpesviruses, based on available ICD-9-CM codes, in a large sample (more than 30,000) of elderly Medicare participants aged 65+. Results:We found that being diagnosed with a herpesvirus (Herpes Simplex, Herpes Zoster or Cytomegalovirus) significantly increased the risk of AD by about 30% in both males and females aged 65+, while vaccination against these viruses did not significantly reduce the AD risk in this sample. We also found that recent time trends in AD risk resemble those reported for the shingles (Herpes Zoster). Conclusions:Results of this study support the hypothesis that AD may be linked to herpesviruses, and suggest that proportion of AD cases associated with the infection can be substantial, though not explaining most of the population risk of AD. Our results also suggest that it may be reasonable to prioritize research on the risk factors for AD that demonstrate behavior and trends consistent with the observed epidemiological trends for AD. The research was supported by the NIH grants P01AG043352 and R01AG046860.
Previous studies in obese individuals indicate higher circulating endocannabinoids anandamide (AE... more Previous studies in obese individuals indicate higher circulating endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) than in lean counterparts. However, the association between plasma endocannabinoids and autonomic control of blood pressure and heart rate has not been assessed in obesity. In a sample of normotensive, obese older adults we analyzed plasma content of the endocannabinoids AEA and total AG using mass spectrometry and examined correlations with various indices of spontaneous sympathovagal activity. Spontaneous baroreflex sensitivity (BRS) for heart rate control was calculated by spectral analysis of arterial pressure (AP) time (Sequence [Seq] Up, Seq Down and Seq All) and frequency (low-frequency [LF] and high-frequency [HF] α) domains from continuous resting AP recordings. In addition, time domain analysis was used to calculate heart rate variability (HRV) and blood pressure variability, indices of cardiac vagal tone and vascular sympathetic tone, respectively. The sample included 8 males and 17 females with a mean age of 68.4 ± 0.6 years, a mean body mass index of 35.0 ± 0.8 kg/m 2 , and mean AP of 101.0 ± 2.2 mmHg. Across the complete sample, we report a significant inverse correlation between plasma AG content and HFα, an index of the vagally-mediated parasympathetic spontaneous BRS ( r = -0.50, P &amp;amp;lt; 0.05). We further report a significant inverse correlation between plasma AG and the vagal spontaneous BRS (Seq Up) in males ( r = -0.87, P &amp;amp;lt; 0.01) but not in females. However, in females but not males we found significant positive relationships between AEA and LFα, an index of sympathetic spontaneous BRS ( r = 0.49, P &amp;amp;lt; 0.05), and AEA and HRV ( r = 0.50, P &amp;amp;lt; 0.05). These results are consistent with a role for the endocannabinoid system to modulate autonomic control of the circulation in populations at risk for hypertension and cardiovascular disease, and suggest gender differences that have yet to be elucidated.
Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovasc... more Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease. Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2295 participants (mean age: 74 years; 52% female; 40% black) from the Health, Aging, and Body Composition Study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1: 869Ϯ376 cm/s; tertile 2: 901Ϯ394 cm/s; tertile 3: 938Ϯ415 cm/s; Pϭ0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional cardiovascular disease risk factors (Pϭ0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, antihypertensive and antilipemic medications, and C-reactive protein, the association with ox-LDL was attenuated but remained significant (Pϭ0.01). Results were similar when ox-LDL was expressed in absolute (milligrams per deciliter) or relative amounts (percentage of low-density lipoprotein). Moreover, individuals in the highest ox-LDL tertile were 30% to 55% more likely to have high arterial stiffness, defined as aPWV Ͼ75th percentile (PՅ0.02). In conclusion, we found that, among elderly persons, elevated plasma ox-LDL levels were associated with higher arterial stiffness, independent of cardiovascular disease risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness. (Hypertension. 2009;53:846-852.) Key Words: aging Ⅲ epidemiology Ⅲ aortic stiffness Ⅲ pulse wave velocity Ⅲ oxidative stress A rterial stiffening, one of the most significant manifestations of vascular aging, is a complex process involving extracellular matrix proteins and smooth muscle cells. 1,2 Arterial stiffness has traditionally been linked to structural alterations in the vascular wall, including fragmentation and degeneration of elastin, increases in collagen content, arterial wall thickening, and luminal dilation. These age-related changes have adverse effects on cardiovascular health, for arterial stiffness increases systolic and pulse pressures, promotes left ventricular hypertrophy and dysfunction, and impairs coronary blood flow. 3,4 Moreover, increased arterial stiffness is associated with increased risk for cardiovascular disease (CVD) and its sequelae, including heart failure, stroke, atherosclerosis, myocardial infarction, and mortality. 1,3,5-10 Although the exact mechanisms underlying arterial stiffening are not well understood, the imbalance in oxidants and
Background-Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have bee... more Background-Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have been implicated in a number of chronic diseases. Previous studies indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However, the reasons for these differences are unclear. Purpose-We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk. Methods-Serum levels of total sRAGE, endogenous secretory RAGE (esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were measured in 99 Blacks and 454 Whites. Results-Blacks had a more adverse cardiovascular risk profile, as well as lower median levels of total sRAGE (972 vs. 1564 pg/ml) and esRAGE (474 vs. 710 pg/ml) compared to Whites (p<0.0001). In addition, the proportion of esRAGE was higher in Blacks (47% vs. 44%, p=0.02), as were the CML/total sRAGE (0.89 vs. 0.56 ng/pg) and CML/esRAGE (1.72 vs. 1.20 ng/pg)
Biologic aging reflects the genetic, molecular, and cellular changes underlying the development o... more Biologic aging reflects the genetic, molecular, and cellular changes underlying the development of morbidity and mortality with advancing chronological age. As several potential mechanisms have been identified, there is a growing interest in developing robust measures of biologic age that can better reflect the underlying biology of aging and predict age-related outcomes. To support this endeavor, the Research Centers Collaborative Network (RCCN) conducted a workshop in January 2022 to discuss emerging concepts in the field and identify opportunities to move the science forward. This paper presents workshop proceedings and summarizes the identified research needs, priorities, and recommendations for measuring biologic age. The highest priorities identified were the need for more robust measures, longitudinal studies, multidisciplinary collaborations, and translational approaches.
<p>Table values are Spearman correlation coefficients (r).</p><p>*p<0.05,<... more <p>Table values are Spearman correlation coefficients (r).</p><p>*p<0.05,</p>†<p>p≤0.0001;</p><p>Abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028410#pone-0028410-t001" target="_blank">Table 1</a>.</p
BACKGROUND Experimental studies in animals suggest that circulating soluble receptor for advanced... more BACKGROUND Experimental studies in animals suggest that circulating soluble receptor for advanced glycation end products (sRAGE) decrease oxidative stress, inflammation, and fibrosis. The association between sRAGE and incident heart failure has not been systematically examined in a prospective study. METHODS We conducted a prospective analysis of a subsample of 1,086 participants from the Atherosclerosis Risk in Communities Study who attended visit 2 (1990-1992) without a history of coronary heart disease, stroke, or heart failure and with measured plasma sRAGE levels. Incident heart failure was defined as death from heart failure or hospitalization due to heart failure during a median of 20 years of follow-up. RESULTS In this sample of a community-based population (mean age 63 years, 60% women, 78% white), there were 126 incident cases of heart failure. Lower levels of sRAGE were significantly associated with an increased risk of heart failure; the adjusted hazard ratios (95% CIs) ...
Aging affects men and women differently; however, the impact of sex and gender on the aging proce... more Aging affects men and women differently; however, the impact of sex and gender on the aging process is not well understood. Moreover, these two concepts are often conflated which further contributes to a lack of clarity on this important issue. In an effort to better understand the relevance of sex and gender in aging research, the Research Centers Collaborative Network (RCCN) sponsored a 1.5-day conference on sex and gender differences in aging that brought together key thought leaders from the six National Institute on Aging center programs. The meeting included sessions on comparing males and females, pathophysiological differences, sex/gender in clinical care, and gender and health in the social context. Presenters from a wide array of disciplines identified opportunities for multidisciplinary research to address current gaps in the field and highlighted the need for a more systematic approach to understanding the how and why of sex/gender differences, as well as the health impl...
BackgroundKetogenic diets have been used to treat both obesity and neurological disorders, includ... more BackgroundKetogenic diets have been used to treat both obesity and neurological disorders, including epilepsy and more recently Alzheimer’s disease (AD), likely due to favorable effects on both central and peripheral metabolism. Improvements in body composition have also been reported; however, it is unclear if diet-induced changes in adiposity are related to improvements in AD and related neuropathology.PurposeWe examined the effects of a Modified Mediterranean Ketogenic (MMK) diet vs. an American Heart Association (AHA) diet on body weight, body composition, and body fat distribution and their association with cerebrospinal fluid (CSF) biomarkers in older adults at risk for AD.MethodsTwenty adults (mean age: 64.3 ± 6.3 years, 35% Black, 75% female) were randomly assigned to a crossover trial starting with either the MMK or AHA diet for 6 weeks, followed by a 6-week washout and then the opposite diet for 6 weeks. At baseline and after each diet adiposity was assessed by dual-energy...
Diabetes is a potent risk factor for dementia, including Alzheimer's disease (AD) and vascula... more Diabetes is a potent risk factor for dementia, including Alzheimer's disease (AD) and vascular dementia, but the mechanisms underlying this association remain unclear. We review current evidence regarding fluid biomarkers that are associated with both AD and type 2 diabetes mellitus, as well as with closely related conditions such as prediabetes and insulin resistance. We also discuss current gaps in knowledge and methodological considerations for future studies. The identification of valid and reliable biomarkers for diabetes-related dementia that can be measured in blood products or cerebrospinal fluid can enhance our understanding of shared disease mechanisms or serve as predictors of risk, clinical progression, or treatment response. Such knowledge would provide critical insight into the basis for their association in epidemiological and population-based studies, as well as suggest strategies for treatment and prevention.
Uploads
Papers by Tina Brinkley