Neighborhood crime is differentially associated with cardiovascular risk factors as a function of race and sex

Background: Neighborhood crime may be an important factor contributing to cardiovascular health disparities, and these relations may vary by race and sex. The present investigation evaluated (a) potential differential associations between neighborhood crime and cardiovascular disease (CVD) risk factors within subgroups of African American (AA) and White men and women, and (b) potential mediation by negative affect. Design and Methods: Participants were 1,718 AAs and Whites (58% AA; 54% female; 59% above poverty; ages 30-64 years) living in Baltimore, Maryland who completed the first wave of the Healthy Aging in Neighborhoods of Diversity across the Life Span study from 2004-2009. CVD risk factors included body mass index, total serum cholesterol, glucose, and systolic and diastolic blood pressure. A negative affect composite was comprised of self-reported depression, anxiety, anger, vigilance, and perceived stress. Hierarchical multiple regression analyses were used to examine associations between per capita overall and violent crime rates, negative affect, and CVD risk factors. Results: There were significant associations of greater overall crime rate with higher fasting glucose (b=.192, P<0.05), and greater violent crime rate with higher systolic (b=86.50, P<0.05) and diastolic (b=60.12, P<0.05) blood pressure in AA women, but not men. These associations were not explained by negative affect. In Whites, there were no significant associations of overall or violent crime rates with cardiovascular risk factors. Conclusions: AA women may be particularly vulnerable to the negative impact of crime on cardiovascular risk. Preventative efforts aimed toward this group may help to deter the detrimental effects that living in a high crime area may have on one’s cardiovascular health

Vitamin D and Biomarkers of Sex Steroid Hormones Are Non-Linearly and Inversely Related to All-Cause Mortality: Results from NHANES III

Background: In men, hypovitaminosis D as well as high and low testosterone levels have been linked to adverse events, including death. A biological interaction has been previously suggested between vitamin D and androgens. In a cohort study using Third National Health and Nutrition Examination Survey data, we simultaneously investigated circulating vitamin D and biomarkers of sex steroid hormones as predictors of all-cause mortality. Methods: Age-adjusted and fully-adjusted Cox regression models were constructed to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Whereas the vitamin D sufficient group (25(OH)D3 ≥30 ng/ml) was selected as a referent, biomarkers of sex steroid hormones (testosterone, estradiol, SHBG) were defined as Loge-transformed continuous variables. Results: Of 1,472 men with a mean age of 42.1 years at baseline, 382 died over a median of 192 months of follow-up. Estradiol levels were significantly higher among vitamin D deficient compared to vitamin D sufficient men and sex hormone binding globulin level was significantly higher in vitamin D sufficient compared to vitamin D insufficient or deficient groups. An inverse non-linear relationship was observed between all-cause mortality rate and levels of testosterone, estradiol and vitamin D, in fully-adjusted models. There were no significant interaction effects between vitamin D and sex steroid hormones in relation to all-cause mortality rate. Conclusions: Vitamin D and sex steroid hormones, but not sex hormone binding globulin, may be inversely and non-linearly related to all-cause mortality among adult men, after adjustment for baseline demographic, socioeconomic, lifestyle and clinical characteristics

Vitamin D receptor and megalin gene polymorphisms are associated with central adiposity status and changes among US adults

We examined longitudinal associations of vitamin D receptor (VDR) and megalin (LRP2; LDL receptor-related protein-2) gene polymorphisms with central adiposity. We used data from the Baltimore Longitudinal Study of Aging (BLSA), an ongoing prospective open cohort study. Study participants consisted of non-Hispanic white adults residing in Baltimore city, with one or more visits at age ≥50 years, and complete data (n 609–617). Repeated assessments on waist circumference (WC) and waist:hip ratio (WHR) were available. Multiple linear mixed models were used to estimate mid-follow-up age central adiposity level and annual rate of change with cut-points set at the sex-specific 80th percentile. The four binary outcomes were: ‘elevated central adiposity’ (ECA-WC and ECA-WHR) and ‘significant increase in central adiposity’ (SICA-WC and SICA-WHR). SNP for VDR (four SNP: (1) rs11568820 (CdX-2:T/C); (2) rs1544410 (BsmI:G/A); (3) rs7975232 (ApaI:A/C); (4) rs731236 (TaqI:G/A)) and Megalin (three SNP: (1) rs3755166:G/A; (2) rs2075252:C/T; (3) rs4668123:C/T) genes were selected. SNP latent classes (SNPLC) and SNP haplotypes (SNPHAP) were created. Multiple logistic regression analyses indicated that, in men, higher ECA-WHR odds were associated with SNPLC Megalin2:rs3755166[–]/rs2075252[TT]/rs4668123[T–] (v. Megalin1:rs3755166[–]/rs2075252[CC]/rs4668123[–]) (OR 2·87; 95 % CI 1·15, 7·12; P = 0·023) and that SNPLC Megalin3:rs3755166[–]/rs2075252[CT]/rs4668123[–] (v. Megalin1) was linked to lower SICA-WC odds (OR 0·48; 95 % CI 0·26, 0·88; P = 0·019) (P > 0·05 for sex × SNPLC). In women, VDR3 SNPHAP (GAA:bAT) was related to lower odds of ECA-WC (OR 0·37; 95 % CI 0·16, 0·87; P = 0·023) (P 0·05 for sex × SNPHAP). Vitamin D-related gene polymorphisms were associated with central adiposity status and change. Future mechanistic studies are needed to confirm those polymorphisms' biological significance to central adiposity

Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence

Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life-extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR-20a, miR-34a, miR-130a, miR-106b, miR-125, and let-7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1- dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease

Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women

Background. Since high sensitivity C-reactive protein (hsCRP) is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD) etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2 ὔ deoxyguanosine (8-oxodG) and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF) may have a role in CVD. Methods and Results. We examined BDNF levels in 3 groups of women that were age-and race-matched with low (<3 mg/L), mid (>3-20 mg/L), and high (>20 mg/L) hsCRP ( = 39 per group) and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. Conclusion. We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3 mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP

Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

<p>Abstract</p> <p>Background</p> <p>The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on <it>ad libitum </it>(AL) feeding with a group on lifespan-extending 40% calorie restriction (CR).</p> <p>Results</p> <p>We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis.</p> <p>Conclusion</p> <p>Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.</p

Systemic Inflammation Is Associated With Longitudinal Changes in Cognitive Performance Among Urban Adults

Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race.Patients/Methods: Among 1,555–1,719 White and African-American urban adults [Agebase: 30–64y, 2004-2013, mean±SD follow-up time(y): 4.64 ± 0.93y], conducted linear mixed-effects regression models were conducted to test associations of inflammatory markers [C-reactive protein, Erythrocyte Sedimentation Rate (ESR), albumin, iron, and an inflammation composite score (ICS)] with longitudinal cognitive performance.Results: Among key findings, CRP was linked to poorer baseline mental status among younger women (≤50y, γ01 = –0.03 ± 0.01, p = 0.002) and poorer attention in older women (&gt;50y, γ01 = −0.024 ± 0.007, p &lt; 0.004) and African-Americans (γ01 = −0.029 ± 0.008, p &lt; 0.001). ESR was related to faster decline on verbal memory among older men (&gt;50y, γ11 = −0.008 ± 0.003, P = 0.009); with poorer performance on attention tests overall (γ01 = −0.010 ± 0.003, P = 0.003) and among African-Americans (γ01 = −0.013 ± 0.004, P = 0.002); on verbal fluency among older women (&gt;50y,γ01 = −0.037 ± 0.013, P = 0.004) and on executive function: overall (γ01 = +0.62 ± 0.21, P = 0.004), older men (&gt;50y, γ01 = +1.69 ± 0.53, P = 0.001) and African-Americans (γ01 = +0.84 ± 0.28, P = 0.002). Albumin was linked to slower attention decline among older men (&gt;50y, γ11 = +0.329 ± 0.103, P = 0.009), over-time improvement in executive function overall (γ11 = −6.00 ± 2.26, P = 0.008), and better baseline psychomotor speed among African-Americans (γ01 = +0.56 ± 0.19, P = 0.003). Finally, ICS predicted faster decline on visual memory/visuo-constructive abilities among older men (&gt;50y, γ11 = +0.17 ± 0.06, p = 0.003).Conclusion: In sum, strong associations between systemic inflammation and longitudinal cognitive performance were detected, largely among older individuals (&gt;50y) and African-Americans. Randomized trials targeting inflammation are warranted

Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender

The transcriptional profiles of five regions of the central nervous system (CNS) of mice varying in age, gender and dietary intake were measured by microarray. The resulting data provide insights into the mechanisms of age-, diet- and gender-related CNS plasticity and vulnerability in mammals

Genetic Variants in Platelet Factor 4 Modulate Inflammatory and Platelet Activation Biomarkers

African Americans suffer from higher prevalence and severity of atherosclerosis compared to Whites, highlighting racial and ethnic disparities in cardiovascular disease. Previous studies have pointed to the role of vascular inflammation and platelet activation in the formation of atherosclerotic lesions