This study examined the relationship between financial strain, or difficulty acquiring necessities, and malnutrition risk in a community dwelling sample of frail and nonfrail women aged 70–79 in the Women’s Health and Aging Study (n = 679). Malnutrition risk was measured with a modified version of the Mini-Nutritional Assessment Short Form (MNA-SF) and defined as a score <11, financial strain was measured by (1) sufficiency of money on a monthly basis and (2) adequacy of income for food, and income was measured by ordinal categories. Mean (SD) modified MNA-SF score was 12.2 (1.80), and 14.7% of women had malnutrition risk. Women who usually did not have enough money to make ends meet had more than four-fold increased odds of malnutrition risk (OR = 4.54; 95% CI: 2.26, 9.14) compared to their counterparts who had some money left over each month. This was only slightly attenuated after control for income and education, (OR = 4.08; 95% CI: 1.95, 8.52) remaining robust. These results show an association between financial strain and malnutrition risk, independent of income, in older women. Self-reported financial strain may be preferable to income as a screener for malnutrition risk in older adults in clinical and research settings.
Background & Aims
Chronic inflammation impairs recovery among the 1.6 million people who suffer from hip fracture annually. Vitamin E and the carotenoids are two classes of dietary antioxidants with profound anti-inflammatory effects, and the goal of this study was to assess whether higher post-fracture concentrations of these antioxidants were associated with lower levels of interleukin 6 (IL-6) and the soluble receptor for tumor necrosis factor-alpha (sTNF-αR1), two common markers of inflammation.
Serum concentrations of the dietary antioxidants and inflammatory markers were assessed at baseline and 2, 6, and 12 month follow-up visits among 148 hip fracture patients from The Baltimore Hip Studies. Generalized estimating equations modeled the relationship between baseline and time-varying antioxidant concentrations and inflammatory markers.
Higher post-fracture concentrations of vitamin E and the carotenoids were associated with lower levels of inflammatory markers. Associations were strongest at baseline, particularly between the α-tocopherol form of vitamin E and sTNF-αR1 (p=0.05) and total carotenoids and both sTNF-αR1(p=0.01) and IL-6 (p=0.05). Higher baseline and time-varying α-carotene and time-varying lutein concentrations were also associated with lower sTNF-αR1 at all post-fracture visits (p ≤ 0.05).
These findings suggest that a clinical trial increasing post-fracture intake of vitamin E and the carotenoids may be warranted.
antioxidants; inflammation; vitamin E; carotenoids; micronutrients; hip fracture
Dry eye disease affects women twice as often as men, but there is little information on whether dry eye treatments, treatment satisfaction, or the impact of dry eye disease on patients’ lives and vision might differ by sex.
Questionnaire survey of 4000 participants in the Women’s Health Study and the Physicians’ Health Studies I and II with a prior report of a diagnosis of DED.
Among participants who re-confirmed a diagnosis of dry eye disease, we assessed symptoms, treatments, patient satisfaction and impact of dry eye disease, and analyzed differences between men and women using regression models.
The final study population consisted of 1,518 women (mean age 70.7 years) and 581 men (mean age 76.7 years), with a mean reported duration of dry eye disease of 10.5 years and 10.1 years, respectively. The frequency and severity of dry eye disease symptoms were higher among women (each P<0.0001), and women reported a greater impact on everyday activities (P<0.0001). Women were more likely to use artificial tears (P<0.0001) use them more often (P<0.0001), and to use Restasis® (P<0.0001), omega-3 fatty acids (P=0.0006), and have punctal occlusion (P=0.005). Women spent more money per month on dry eye treatments (P<0.0001), but reported greater dissatisfaction with treatment side effects (P=0.001), and the amount of time before treatments started working (P=0.03).
These data show that dry eye disease is generally experienced as being more severe among women, having a greater impact on their self-assessed well-being.
To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older, community-dwelling adults.
Plasma selenium, CML, folate, vitamin B12, testosterone, and markers of iron status and inflammation were measured at baseline in 1,036 adults, ≥65 years, in the InCHIANTI Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relationship to prevalent anemia and incident anemia over 6 years of follow-up.
At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment 72 (15.3%) developed anemia within 6 years of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 μg/L) predicted incident anemia (Hazards Ratio [H.R.] 1.67, 95% Confidence Interval [C.I.] 1.07–2.59, P = 0.02; H.R. 1.55, 95% C.I.1.01–2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases.
Elevated plasma carboxymethyl-lysine and low plasma selenium are long-term independent predictors of anemia among older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia.
advanced glycation end products; aging; anemia; carboxymethyl-lysine; oxidative stress; selenium
We report the case of an 18-year-old male who developed both nutritional amblyopia and night blindness. After nearly a lifetime of consuming a bizarre diet limited to French fries, pretzels, crackers, and carbonated sodas, he had a relatively sudden onset of night blindness and bilateral visual loss. The night blindness resolved after taking daily oral vitamin A supplements. Visual acuity gradually improved from light perception, both eyes, to 20/20 right eye and 20/25 left eye after multivitamin supplementation and vitamin B12 injections. The patient had bilateral optic atrophy and bilateral ring scotomas around a small area of fixation. The patient was unable to modify his diet despite professional advice and counseling.
B complex vitamins; Nutritional amblyopia; Night blindness; Vitamin A
The aging suppressor gene klotho encodes a single-pass transmembrane protein klotho that in mice is known to extend life span when overexpressed and to resemble accelerated aging, with skeletal muscle atrophy and decreased bone mineral density, when expression is disrupted. We sought to examine the relationship between plasma klotho and disability in activities of daily living (ADL) in older community-dwelling adults. In a cross-sectional study, plasma klotho was measured in a population-based sample of 802 adults, ≥65 years, who participated in the “Invecchiare in Chianti” (Aging in the Chianti Area) (InCHIANTI) study in Tuscany, Italy. The overall proportion of adults with ADL disability was 11.9%. Mean (standard deviation) klotho concentrations were 689 (238) pg/mL. From the lowest to the highest tertile of plasma klotho, 16.1%, 9.7%, and 5.6% of participants, respectively, had ADL disability (p=0.0004). Plasma klotho, per 1 standard deviation increase, was associated with ADL disability (odds ratio=0.57, 95% confidence interval 0.35–0.93, p=0.02) in a multivariate logistic regression model adjusting for age, education, cognition, physical activity, physical performance, total cholesterol, alcohol and tobacco use, and chronic diseases. Low plasma klotho concentrations were independently associated with ADL disability among older community-dwelling men and women.
Recent studies have expanded the functions of vitamin D to a possible role in pulmonary function. Our objective was to examine the relationship between serum 25-hydroxyvitamin D (25[OH]D), serum parathyroid hormone, and pulmonary function in older women.
We examined the relationship of serum 25(OH)D and parathyroid hormone with pulmonary function (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio) in a cross-sectional study of 646 moderately to severely disabled women, 65 years or more, living in the community in Baltimore, Maryland, who participated in the Women’s Health and Aging Study I.
Overall, median (25th, 75th percentile) serum 25-hydroxyvitamin D concentrations were 19.9 (14.7, 26.7) ng/mL. Serum 25(OH)D was positively associated with FEV1 (p = .03), FVC (p = .18), and FEV1/FVC (p = .04) in multivariable linear regression models adjusting for age, race, education, smoking, height, physical activity, cognition, interleukin-6, chronic diseases, and other potential confounders. In the same models, serum parathyroid hormone was not significantly associated with FEV1, FVC, or FEV1/FVC.
These findings support the idea that vitamin D deficiency is independently associated with poor pulmonary function in older disabled women.
Aging; Lung function; Parathyroid hormone; Vitamin D; Women
Frailty is a dynamic geriatric syndrome characterized by decreased reserve and increased vulnerability. Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in older adults are associated with many physiological changes that portend frailty and its consequences. We aimed to assess whether serum 25(OH)D concentrations relate to transitions between the states of robustness, prefrailty, and frailty, and to mortality.
DESIGN, SETTING, and PARTICIPANTS
Adults aged≥65 years (N=1,155) enrolled in Invecchiare in Chianti (InCHIANTI), a prospective cohort study in Tuscany, Italy.
Serum 25(OH)D concentrations measured at baseline and frailty state (robust, prefrail, frail) assessed at baseline and at three and six years post enrollment. Vital status was also determined at three and six years post enrollment.
The median (interquartile range) 25(OH)D concentration was 16.0 (10.4—25.6) ng/mL (multiply by 2.496 to convert to nmol/L). Prefrail participants with 25(OH)D<20 ng/mL were 8.9% (95% Confidence Interval [CI], 2.5—15.2%) more likely to die, 3.0% (95%CI, −5.6—14.6%) more likely to become frail, and 7.7% (95%CI, −3.5—18.7%) less likely to become robust than prefrail participants with 25(OH)D≥20 ng/mL. Among prefrail participants, each 5 ng/mL decrement of continuous 25(OH)D was associated with 1.46 times higher odds of dying (95%CI, 1.18—2.07) and 1.13 higher odds of incident frailty (95%CI, 0.90—1.39) versus recovery of robustness. Transitions from robustness or frailty were not associated with 25(OH)D.
Results provide evidence that prefrailty is an “at risk” state from which older adults with high 25(OH)D are more likely to recover than to decline. However, high 25(OH)D was not associated with recovery from frailty. Thus, 25(OH)D should be investigated as a potential therapy to treat prefrailty and prevent further decline.
Frailty; Mortality; Vitamin D
In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65495–503-specific CD8+ T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65495–503-specific CD8+ T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65495–503 tetramer-positive CD8+ T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p < 0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8+ T cells specific for the CMV immunodominant epitope pp65495–503. Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.
Monocytic CMV DNA; CMV pp65495–503-specific CD8+ T cells; CMV IgG serology; Older adults
We examined the cross-sectional and longitudinal relationship between plasma carotenoids and depressive symptoms over a six-year follow-up in older persons.
Methods and Materials
This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 958 women and men aged 65 years and older. Plasma total carotenoids were assessed at baseline. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-up using the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D≥20.
At baseline, higher total carotenoids level were associated with lower probability of depressed mood (OR=0.82, 95%CI=0.68–0.99, p=0.04) after adjustment for sociodemographic, health and inflammation. After the exclusion of participants with baseline depressed mood and use of antidepressants, higher total carotenoids level were associated with lower risk of incident depressed mood (OR=0.72, 95%CI=0.52–0.99, p=0.04) at 6-year follow-up, after adjustment for confounders plus baseline CES-D. Inflammatory marker Interleukin-1 receptor antagonist partially mediated this association.
Low plasma concentrations of carotenoids are associated with depressive symptoms and predict the development of new depressive symptoms in older persons. Understanding the mechanism of this association may reveal potential targets for prevention and treatment.
Carotenoids; antioxidants; depression; inflammation; aging
Although fibroblast growth factor 23 (FGF23) has been implicated in the pathogenesis of cardiovascular disease, the relationship between FGF23 and cardiovascular disease has not been well characterized in the general population. The aim of the study was to determine whether serum FGF23 is independently associated with cardiovascular disease in older community-dwelling women.
Design and methods
A cross-sectional design was used to examine the relationship between serum FGF23 and cardiovascular disease. The subjects consisted of a population-based sample of 659 women, aged 70–79 years, who participated in the Women’s Health and Aging Studies in Baltimore, Maryland. Prevalent cardiovascular disease (coronary heart disease, stroke, congestive heart failure, peripheral artery disease) was assessed through diagnostic algorithms and physician adjudication.
Of the 659 women, 185 (28.1%) had cardiovascular disease. Median (25th, 75th percentile) intact serum FGF23 was 34.6 (25.2, 46.2) pg/mL. The prevalence of cardiovascular disease in the lowest, middle, and highest tertile of serum FGF23 was 22.6%, 24.9%, and 36.7%, respectively (P = 0.002). Serum log FGF23 was associated with cardiovascular disease (Odds Ratio per 1 SD increase = 1.23, 95% Confidence Interval 1.17, 1.30; P <0.0001) in a multivariable logistic regression model, adjusting for age, race, smoking, education, body mass index, cognition, diabetes, hypertension, physical activity, total cholesterol, HDL cholesterol, and renal function.
Elevated serum FGF23 concentrations are independently associated with prevalent cardiovascular disease in older community-dwelling women. Further studies are needed to elucidate the potential biological mechanisms by which FGF23 may be involved in the pathogenesis of cardiovascular disease.
aging; cardiovascular disease; fibroblast growth factor 23; women
To determine whether plasma klotho, a recently discovered hormone that has been implicated in atherosclerosis, is related to prevalent cardiovascular disease in adults.
Population-based sample of adults residing in Tuscany, Italy.
One thousand and twenty-three men and women, aged 24–102, participating in the Invecchiare in Chianti (InCHIANTI) study.
Anthropometric measures, plasma klotho, fasting plasma total, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine, C-reactive protein. Clinical measures: medical assessment, diabetes mellitus, hypertension, coronary heart disease, heart failure, stroke, peripheral artery disease, cancer, chronic kidney disease. Logistic regression models were used to examine the relationship between plasma klotho and prevalent cardiovascular disease.
Of 1023 participants, 259 (25.3%) had cardiovascular disease. Median (25th, 75th percentile) plasma klotho concentrations were 676 (530, 819) pg/mL. Plasma klotho was correlated with age (r = −0.14, P <0.0001), HDL cholesterol (r = 0.11, P = 0.0004), C-reactive protein (r = −0.10, P = 0.0008), but not systolic blood pressure, fasting plasma glucose, or renal function. Plasma klotho age-adjusted geometric means (95% Confidence Interval [C.I.]) were 626 (601, 658) in participants with cardiovascular disease and 671 (652, 692) pg/mL in those without cardiovascular disease (P = 0.0001). Adjusting for traditional cardiovascular risk factors (age, sex, smoking, total cholesterol, HDL cholesterol, systolic blood pressure, and diabetes), log plasma klotho was associated with prevalent cardiovascular disease (Odds Ratio per 1 standard deviation increase = 0.85, 95% C.I. 0.72, 0.99).
In community-dwelling adults, higher plasma klotho concentrations are independently associated with a lower likelihood of having cardiovascular disease.
aging; atherosclerosis; cardiovascular disease; C-reactive protein; klotho
Advanced glycation end products (AGEs) are implicated in the pathogenesis of atherosclerosis, diabetes, and kidney disease. The objective was to describe dietary intake, the dominant source of exposure to AGEs, with carboxymethyl-lysine (CML), a major AGE, in serum and urine, respectively.
Serum and urinary CML were measured in 261 adults, aged 21–69 years, and compared with diet as assessed by six separate 24-hour dietary recalls.
Median (25th, 75th percentile) serum and urinary CML concentrations were 686 (598, 803 μg/L) and 1023 (812, 1238) μg/gm creatinine. There was no correlation between serum and urinary CML (r = −0.02, P = 0.78). Serum CML was positively correlated with intake of soy, fruit juice, cold breakfast cereal, non-fat milk, whole grains, fruit, non-starchy vegetables, and legumes, and negatively correlated with intake of red meat. Intake of fast food was not significantly correlated with serum CML. Urinary CML was positively correlated with intake of starchy vegetables, whole grains, sweets, nuts/seeds, and chicken, and negatively correlated with intake of fast foods. Intake of AGE-rich foods such as fried chicken, French fries, bacon/sausage, and crispy snacks were not significantly correlated with serum or urinary CML, except for a significant negative correlation between fried chicken and serum CML.
These findings suggest that the high consumption of foods considered high in CML is not a major determinant of either serum or urinary CML. Further work is needed to understand the relationship of AGEs in blood and urine with the metabolism of dietary AGEs.
advanced glycation end products; carboxymethyl-lysine; diet; 24-hour dietary recall; food
Handgrip strength is a strong indicator of total body muscle strength and is a predictor of poor outcomes in older adults. The aging suppressor gene klotho encodes a single-pass transmembrane protein that is secreted as a circulating hormone. In mice, disruption of klotho expression results in a syndrome that includes sarcopenia, atherosclerosis, osteoporosis, and shortened lifespan, and conversely, overexpression of klotho leads to a greater longevity. The objective was to determine whether plasma klotho levels are related to skeletal muscle strength in humans. We measured plasma klotho in 804 adults, ≥65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Grip strength was positively correlated with plasma klotho at threshold <681 pg/mL. After adjusting for age, sex, education, smoking, physical activity, cognition, and chronic diseases, plasma klotho (per 1 standard deviation increase) was associated with grip strength (beta = 1.20, standard error = 0.35, P = 0.0009) in adults with plasma klotho <681 pg/mL. These results suggest that older adults with lower plasma klotho have poor skeletal muscle strength.
aging; klotho; muscle strength; sarcopenia
Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. Our aim was to characterize the relationship between serum carboxymethyl-lysine (CML), a major circulating AGE, and incident severe walking disability (inability to walk or walking speed <0.4 m/sec) over 30 months of followup in 394 moderately to severely disabled women, ≥65 years, living in the community in Baltimore, Maryland (the Women's Health and Aging Study I). During followup, 154 (26.4%) women developed severe walking disability, and 23 women died. Women in the highest quartile of serum CML had increased risk of developing of severe walking disability in a multivariate Cox proportional hazards model, adjusting for age and other potential confounders. Women with elevated serum CML are at an increased risk of developing severe walking disability. AGEs are a potentially modifiable risk factor. Further work is needed to establish a causal relationship between AGEs and walking disability.
Poor nutritional status after hip fracture is common and may contribute to physical function decline. Low serum concentrations of vitamin E have been associated with decline in physical function among older adults, but the role of vitamin E in physical recovery from hip fracture has never been explored.
Serum concentrations of α- and γ-tocopherol, the two major forms of vitamin E, were measured in female hip fracture patients from the Baltimore Hip Studies cohort 4 at baseline and at 2-, 6-, and 12-month postfracture follow-up visits. Four physical function measures—Six-Minute Walk Distance, Lower Extremity Gain Scale, Short Form-36 Physical Functioning Domain, and Yale Physical Activity Survey—were assessed at 2, 6, and 12 months postfracture. Generalized estimating equations modeled the relationship between baseline and time-varying serum tocopherol concentrations and physical function after hip fracture.
A total of 148 women aged 65 years and older were studied. After adjusting for covariates, baseline vitamin E concentrations were positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, and Yale Physical Activity Survey scores (p < .1) and faster improvement in Lower Extremity Gain Scale and Yale Physical Activity Survey scores (p < .008). Time-varying vitamin E was also positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, Yale Physical Activity Survey, and Short Form-36 Physical Functioning Domain (p < .03) and faster improvement in Six-Minute Walk Distance and Short Form-36 Physical Functioning Domain (p < .07).
Serum concentrations of both α- and γ-tocopherol were associated with better physical function after hip fracture. Vitamin E may represent a potentially modifiable factor related to recovery of postfracture physical function.
Vitamin E; Physical function; Hip fracture; Nutrition; Micronutrients
The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans.
We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy.
During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho (<575 pg/mL) had an increased risk of death compared with participants in the highest tertile of plasma klotho (>763 pg/mL; hazards ratio 1.78, 95% confidence interval 1.20–2.63).
In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.
Aging; Klotho; Longevity; Mortality
The relationship of circulating endogenous secretory receptor for advanced glycation end products (esRAGE) and chronic kidney disease (CKD) has not been well characterized. The aim of the study was to determine whether plasma esRAGE is associated with CKD and is predictive of developing CKD in older adults.
The relationship between plasma esRAGE and CKD (more than stage 3 of the National Kidney Foundation classification; estimated glomerular filtration rate <60 ml/min/1.73 m2) and CKD over 6 years of follow-up was examined in a cross-sectional and prospective study design in 1,016 men and women, ≥65 years, in the InCHIANTI study, a population-based cohort study of aging in Tuscany, Italy.
At enrollment, 158 (15.5%) had CKD. Mean (SD) plasma esRAGE was 0.45 (0.24) ng/ml. Plasma esRAGE (ng/ml) was associated with CKD (odds ratio per 1 SD = 1.30; 95% CI 1.1–1.6; p < 0.005) in a multivariable logistic regression model, adjusting for potential confounders. Plasma esRAGE was an independent predictor of incident CKD over 6 years of follow-up (hazard ratio per 1 SD = 1.37; 95% CI 1.1–1.7; p < 0.008) in a multivariable Cox proportional hazards model, adjusting for potential confounders.
Elevated plasma esRAGE is independently associated with CKD and is an independent predictor of incident CKD in older community-dwelling adults.
Advanced glycation end products; Aging; Chronic kidney disease; Endogenous secretory receptor for advanced glycation end products
We examined whether adherence to a Mediterranean-style diet has positive effects on mobility assessed over a nine-year follow-up in a representative sample of older adults. This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 935 women and men aged 65 years and older. Adherence to the Mediterranean diet was assessed at baseline by the standard 10-unit Mediterranean diet score (MDS). Lower extremity function was measured at baseline, and at the 3, 6 and 9-year follow-up visits using the Short Physical Performance Battery (SPPB). At baseline, higher adherence to Mediterranean diet was associated with better lower body performance. Participants with higher adherence experienced less decline in SPPB score, which was of 0.9 points higher (p<.0001) at the 3-year-follow, 1.1 points higher (p= 0.0004) at the 6-year follow-up and 0.9 points higher (p= 0.04) at the 9-year follow-up compared to those with lower adherence. Among participants free of mobility disability at baseline, those with higher adherence had a lower risk (HR=0.71,95%CI=0.51–0.98, p=0.04) of developing new mobility disability. High adherence to a Mediterranean-style diet is associated with a slower decline of mobility over time in community dwelling older persons. If replicated, this observation is highly relevant in terms of public health.
Mediterranean diet; mobility; SPPB; aging
Advanced glycation end products (AGEs) are thought to cause inflammation through interaction with the receptor for AGEs (RAGE), therefore contributing to adverse aging-related processes. The relationship between AGEs, RAGE, and inflammation has not been well characterized.
We examined the relationship of plasma endogenous secretory RAGE (esRAGE); carboxymethyl-lysine (CML), a circulating AGE; and inflammatory mediators in 1,298 adults, 20–97 years, who participated in the InCHIANTI study in Tuscany, Italy. Blood levels of esRAGE, CML, interleukin-1 receptor antagonist (IL-1RA), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, IL-6 receptor (IL-6R), IL-18, C-reactive protein (CRP), transforming growth factor-β (TGF-β), and fibrinogen were measured.
Log plasma esRAGE was associated with log IL-1RA (β = −0.069, SE = 0.036, p = .05) and log IL-6 (β = 0.077, SE = 0.035, p = .03), respectively, in separate multivariable linear regression models, adjusting for potential confounders. Log plasma esRAGE was also negatively associated with log TGF-β but did not reach statistical significance (β = −0.091, SE = 0.053, p = .09). Log plasma esRAGE was not significantly associated with log IL-1β, log TNF-α, IL-6R, log IL-18, or CRP. Log plasma CML was not associated with any of the inflammatory mediators except for IL-6R (β = −14.10, SE = 5.94, p = .02) and fibrinogen (β = 13.95, SE = 7.21, p = .05) in separate multivariable models, adjusting for potential confounders.
Plasma esRAGE is correlated with higher IL-6 and lower IL-1RA. These findings suggest that plasma esRAGE plays a role in modulating inflammation, although the exact mechanisms remain to be elucidated.
Advanced glycation end products; C-reactive protein; Endogenous secretory receptor for advanced glycation end products; Interleukin-1 receptor antagonist; Interleukin-6
We characterized the relationship of the presence of an improved latrine with diarrhea and under-five child mortality in Indonesia. The proportion of rural and urban families, respectively, without an improved latrine was 52.1% and 16.2%, with a child with a history of diarrhea in the last 7 days was 8.2% and 9.7%, and with a history of under-five child mortality was 11.1% and 8.5%. Among rural and urban families, respectively, lack of an improved latrine was associated with a child history of diarrhea in the last 7 days (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.18–1.29, P < 0.0001; OR = 1.20, 95% CI = 1.13–1.27, P < 0.0001) and under-five child mortality (OR = 1.29, 95% CI = 1.25–1.31, P < 0.0001; OR = 1.22, 95% CI = 1.12–1.32, P < 0.0001) in separate multivariable logistic regression models adjusting for covariates. The lack of a household improved latrine is associated with diarrhea and under-five child mortality in Indonesia.
Evidence regarding the health benefits of carotenoids is controversial. Effects of serum carotenoids and their interactions on mortality have not been examined in a representative sample of US adults. The objective was to examine whether serum carotenoid concentrations predict mortality among US adults. The study consisted of adults aged ≥20 years enrolled in the National Health and Nutrition Examination Survey (NHANES) III, 1988–1994, with measured serum carotenoids and mortality follow-up through 2006 (N=13,293). Outcomes were all-cause, cardiovascular disease (CVD), and cancer mortality. In adjusted Cox proportional hazards models, participants in the lowest total carotenoid quartile (<1.01µmol/L) had significantly higher all-cause mortality (mortality rate ratio=1.38; 95% confidence interval:1.15—1.65; P=0.005) than those in the highest total carotenoid quartile (>1.75µmol/L). For alpha-carotene, the highest quartile (>0.11µmol/L) had the lowest all-cause mortality rates (P<0.001). For lycopene, the middle two quartiles (0.29–0.58µmol/L) had the lowest all-cause mortality rates (P=0.047). Analyses with continuous carotenoids confirmed associations of serum total carotenoids, alpha-carotene, and lycopene with all-cause mortality (P<0.001). In a random survival forest analysis, very low lycopene was the carotenoid most strongly predictive of all-cause mortality, followed by very low total carotenoids. Alpha-carotene/beta-cryptoxanthin, alpha-carotene/lutein+zeaxanthin and lycopene/lutein+zeaxanthin interactions were significantly related to all-cause mortality (P<0.05). Low alpha-carotene was the only carotenoid associated with CVD mortality (P=0.002). No carotenoids were significantly associated with cancer mortality. Very low serum total carotenoid, alpha-carotene, and lycopene concentrations may be risk factors for mortality, but carotenoids show interaction effects on mortality. Interventions of balanced carotenoid combinations are needed for confirmation.
alpha-carotene; beta-carotene; beta-cryptoxanthin; carotenoids; human subjects; lycopene; lutein; mortality; NHANES; zeaxanthin
Ischemia-induced retinal NV, vascular leakage, and apoptosis are inhibited in the absence of PHD1 by preventing vessel loss, without which there would be no need to initiate angiogenesis signaling when mice are returned to room air.
Prolyl hydroxylases (PHDs) are oxygen sensors that stabilize hypoxia-inducible factors (HIFs) to induce proinflammatory, vasopermeability, and proapoptotic factors. These may be potential targets to reduce the complications of ischemic retinopathies.
Oxygen-induced ischemic retinopathy (OIR) was generated as a model for retinopathy of prematurity (ROP) by placing 7-day-old mice in 75% oxygen for 5 days and returning them to the relative hypoxia of room air for 5 days. Neovascularization (NV) and avascular areas were assessed on retinal flat-mounts by image analysis. Blood-retinal barrier breakdown was assessed using 3H-mannitol as a tracer. Apoptosis was detected with TUNEL staining. HIF-1α and VEGF were quantified using Western blot analysis and ELISA.
PHD1-deficient mice demonstrated reduced hyperoxia-associated vascular obliteration during oxygen-induced ischemic retinopathy. This was associated with subsequent reduced avascularity, vascular leakage, and pathologic NV during the hypoxic phase, which could be accounted for by a reduced expression of HIF-1α and VEGF. Apoptosis in the retina was also reduced in PHD1-depleted mice after 2 days in hyperoxia.
PHD1 deficiency is associated with a reduction of ischemia-induced retinal NV. The regulatory mechanism in this model appears to be: PHD1 depletion prevents HIF-1α degradation in hyperoxia, which induces VEGF, thus preventing hyperoxia-related vessel loss. Without a vessel deficiency, there would not be relative hypoxia when the mice are returned to room air and there would be no need to initiate angiogenesis signaling. Blocking PHD1 may be beneficial for ischemic retinopathies and inflammatory and neurodegenerative disorders.
Vitamin D deficiency is associated with cardiovascular disease, osteoporosis, poor muscle strength, falls, fractures, and mortality. Although older adults are at a high risk of vitamin D deficiency, the relationship of serum 25(OH)D with all-cause and cardiovascular disease mortality has not been well characterized in the elderly. We hypothesized that low serum 25(OH)D predicted mortality in older adults.
Serum 25(OH)D and all-cause and cardiovascular disease mortality were examined in 1006 adults, ≥65 years, who participated in the InCHIANTI study, a population-based, prospective cohort study of aging in Tuscany, Italy. Serum 25(OH)D was measured at enrollment in 1998-1999, and participants were followed for mortality.
During 6.5 years of follow-up, 228 (22.7%) participants died, of whom 107 died from cardiovascular disease. Compared with participants in the highest quartile of serum 25(OH)D (>26.5 ng/mL)(to convert to nmol/L, multiply by 2.496), those in the lowest quartile (<10.5 ng/mL) had increased risk of all-cause mortality (Hazards Ratio [H.R.] 2.11, 95% Confidence Interval [C.I.] 1.22 – 3.64, P = 0.007) and cardiovascular disease mortality (H.R. 2.64, 95% C.I. 1.14 – 4.79, P = 0.02), in multivariate Cox proportional hazards models that adjusted for age, sex, education, season, physical activity, and other potential confounders.
Older community-dwelling adults with low serum 25(OH)D are at higher risk of all-cause and cardiovascular disease mortality.
Aging; all-cause mortality; cardiovascular disease mortality; vitamin D