Richard D Semba's research while affiliated with Johns Hopkins University and other places
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Publications (520)
Objectives:
Calcific aortic stenosis (AS) is the most common valvular disease in older adults, yet its risk factors remain insufficiently studied in this population. Such studies are necessary to enhance understanding of mechanisms, disease management and therapeutics.
Methods:
The Cardiovascular Health Study is a population-based investigation...
Purpose of Review
Dairy milk products are dominant in the market; however, plant-based milks are gaining prominence among USA consumers. Many questions remain about how plant-based milk products compare to dairy milk from a nutrition, public health, and planetary health perspective. Here, we compare the retail sales, nutrient profiles, and known he...
Although growth/differentiation factor 11 (GDF11), growth/differentiation factor 8 (GDF8), and their circulating antagonists, which include GDF11 and GDF8 propeptides, follistatin (FST), WFIKKN1, and WFIKKN2, have been shown to influence skeletal muscle and aging in mice, the relationship of these circulating factors with human phenotypes is less c...
Purpose:
To analyze the urinary metabolomic profile of central serous chorioretinopathy (CSC) cases.
Methods:
In a cross-sectional study, 80 participants with CSC were compared with 80 age- and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4TM platform.
Results:
Of 1031 metabolites total that were measur...
The specific aim was to characterize retail purchases of red and processed meat and other major protein-rich foods in the U.S. and by state. Supermarket scanner data from grocery stores, supermarkets, and big box stores collected from 2017-2019 (NielsenIQ, New York, NY) was used to characterize retail purchases of red meat, processed meat, and othe...
Background
Cash transfer (CT) programs are an important type of social protection meant to reduce poverty. Whether CT programs increase the risk of overweight and obesity is unclear. The objective was to characterize the relationship between CT programs and the risk of overweight and obesity in children and adults.
Methods
We searched articles in...
Bone fragility can progress with aging, but biomarkers to detect emerging osteopenia have not been fully elucidated. Growth/differentiation factor 15 (GDF-15) has pleiotropic roles in a broad range of age-related conditions, but its association with osteopenia is unknown. We examined the relationship between plasma GDF-15 levels and rate of change...
Background
The pathophysiological mechanisms underlying the association between red blood cell distribution width (RDW) and all-cause mortality are unknown. We conducted a data-driven discovery investigation to identify plasma proteins that mediate the association between RDW and time to death in community-dwelling adults.
Methods
At baseline, 962...
Accumulation of advanced glycation end‐products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non‐fluorescent AGEs. We examined associations of carboxy‐methyl‐lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in t...
Background
Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality.
Methods
642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were follo...
Micronutrient deficiencies are a major cause of morbidity and mortality in low- and middle-income countries worldwide. Climate change, characterized by increasing global surface temperatures and alterations in rainfall, has the capacity to affect the quality and accessibility of micronutrient-rich foods. The goals of this review are to summarize th...
Background: Legumes are an inexpensive, healthy source of protein, fiber, and micronutrients, have low greenhouse gas and water footprints, and enrich soil through nitrogen fixation. Although higher legume consumption is recommended under US dietary guidelines, legumes currently comprise only a minor part of the US diet.
Objectives: To characterize...
Background and objectives
Hypertension is associated with significant morbidity and mortality despite effective antihypertensive therapies. Soluble klotho is a circulating protein that in preclinical studies is protective against the development of hypertension. There are limited studies of klotho and blood pressure in humans.
Design, setting, par...
Background
Although diets rich in carotenoids are associated with reduced risk of cardiovascular disease, age-related macular degeneration, disability, and other adverse aging outcomes, the underlying biological mechanisms are not fully elucidated.
Objectives
To characterize the plasma proteome fingerprint associated with circulating carotenoid an...
Background:
To guide the transformation of food systems to provide for healthy and sustainable diets, countries need to assess their current diet and food supply in comparison to nutrition, health, affordability, and environmental goals.
Objectives:
We sought to compare Indonesia's food utilization to diets optimized for nutritional value and co...
Growth faltering under 5 years of age is unacceptably high worldwide, and even more children, while not stunted, fail to reach their growth potential. The time between conception and 2 years of age is critical for development. The period from 6 to 23 months, when complementary foods are introduced, coincides with a time when growth faltering and de...
Purpose
: To characterize the proteome of the iris in primary angle closure glaucoma (PACG).
Experimental Design
: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analyzed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q...
Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is ass...
Background
Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20–30 ng/mL) for skeletal health.
Objectives
We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults’ physical function.
Methods
Using 5 large prospective,...
The identification of plasma proteins that systematically change with age and, independent of chronological age, predict accelerated decline of health is an expanding area of research. Circulating proteins are ideal translational “omics” since they are final effectors of physiological pathways and because physicians are accustomed to use informatio...
Dietary protein production from animals is a major source of greenhouse gas emissions, water use, and deforestation. Legumes are a rich source of protein but currently comprise a minor part of most human diets. Worldwide, the average consumption of legumes and meat is 21 and 112 g/person/day, respectively. Legumes are part of traditional diets in m...
IntroductionChronic kidney disease (CKD) is an important cause of disability and death, but its pathogenesis is poorly understood. Plasma metabolites can provide insights into underlying processes associated with CKD.Objectives
To clarify the relationship of plasma metabolites with CKD and renal function in human.Methods
We used a targeted metabolo...
Background
Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts th...
Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength and fitness. However, while the decline in these phenotypes have been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mitocho...
Although mitochondrial dysfunction has been implicated in aging, physical function decline, and several age-related diseases, an accessible and affordable measure of mitochondrial health is still lacking. In this study we identified the proteomic signature of muscular mitochondrial oxidative capacity in plasma. In 165 adults, we analyzed the associ...
The COVID-19 pandemic has increased food insecurity, especially among low-income Black and His¬panic families in the United States. Food insecurity is associated with poorer health and higher mortality in adults and greater risk of impaired cognitive development and behavioral problems in children. Pro-viding food for low-income families is an impo...
Background
Advanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.
Obje...
A worldwide shift from current diets to the planetary health diet proposed by the EAT–Lancet Commission would have direct implications for agricultural greenhouse gas (GHG) emissions. By modelling the trajectory of food from cradle to farm gate while accounting for international trade, we estimate that agricultural GHG emissions would decrease in 1...
Background
We sought to identify biomarkers that indicate low turnover on bone histomorphometry in CKD patients, and subsequently determined if this panel identified differential risk for fractures in community-living older adults.
Methods
Among CKD patients who underwent iliac crest bone biopsies and histomorphometry, we evaluated candidate bioma...
Context
αKlotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high FGF23 occur in chronic kidney disease (CKD).
Objective
We aimed to assess relationships of αKlotho and FGF23 with mobility disability in community-dwell...
Background
Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength and fitness but while the decline in these phenotypes have been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mi...
Alzheimer disease (AD), the most common cause of dementia, is a progressive disorder involving cognitive impairment, loss of learning and memory, and neurodegeneration affecting wide areas of the cerebral cortex and hippocampus. AD is characterized by altered lipid metabolism in the brain. Lower concentrations of long-chain PUFAs have been describe...
Introduction:
Mobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data-driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability i...
Dementia is characterized by a long preclinical phase that may last years to decades before the onset of mild cognitive impairment. Slow gait speed and subjective memory complaint commonly co-occur during this preclinical phase, and each is a strong independent predictor of cognitive decline and dementia. Motoric cognitive risk (MCR) syndrome is a...
A decline of skeletal muscle strength with aging is a primary cause of mobility loss and frailty in older persons, but the molecular mechanisms of such decline are not understood. Here, we performed quantitative proteomic analysis from skeletal muscle collected from 58 healthy persons aged 20 to 87 years. In muscle from older persons, ribosomal pro...
Serum amino acid (AA) concentrations are correlated with childhood stunting, but their relation to linear growth velocity has not been explored. This was a secondary analysis of a clinical trial where Malawian infants aged 6-12 mo were given a legume supplement providing 8.2 g/d of protein; anthropometry was conducted at multiple intervals, and fas...
A progressive decline of skeletal muscle strength with aging is a primary cause of mobility loss and frailty in older persons, but the molecular mechanisms of such decline are not fully understood. Here, using quantitative discovery proteomic data from skeletal muscle specimens collected from 58 healthy persons aged 20 to 87 years show that ribosom...
Sarcopenia, the progressive loss of muscle mass, strength, and physical performance that occurs during aging, is highly prevalent among the elderly. Sarcopenia increases the risk of falls, disability, and death. The biological basis for sarcopenia is not well understood. There are no specific preventive or therapeutic strategies for sarcopenia exce...
Background
Growth and differentiation factor-15 (GDF-15) has been associated with obesity, muscle wasting, and cachexia. The receptor for GDF-15 was recently identified in the brainstem and regulates food intake and metabolism. The relationship of plasma GDF-15 with the age-associated decline of muscle mass and strength, gait speed, and physical pe...
The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cogni...
Background
Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach.
Methods
In a case-control study, 240 adults, age...
High protein diets may increase the intake and accumulation of advanced glycation endproducts (AGEs) which promote adverse health effects. However, direct evidence that high protein diets increase AGEs is lacking. We examined whether dietary protein intake is associated with serum levels of the major AGE carboxymethyl-lysine (CML) and the soluble r...
Background
Growth/differentiation factors 8 (GDF8) and 11 (GDF11) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be affected by circulating antagonists such as their respective prodomains, follistatin (FST315), WFIKKN1, and WFIKKN2. Reports of the relationship of GDF8 and GDF11 and...
Background:
In the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Further, we examined whether this association differs by HIV serostatus and race.
Methods:
Of 715 men assessed for frailty and selected f...
Background:
Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarker...
To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22–93 years old, who were disease‐ and treatment‐free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10⁻⁵ significance threshold,...
Context and Objectives
Glucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults.
Participant...
Background
Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of ch...
Background & aims:
Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART ini...
The human eye is a complex organ consisting of multiple compartments with unique and specialized properties that reflect their varied functions. Although there have been advancements in ocular imaging and therapeutics over the past decade, the pathogenesis of many common eye diseases remains poorly understood. Proteomics is an invaluable tool to ga...
Idiopathic macular holes (IMH) are full-thickness defects of retinal tissue that cause severe vision loss due to disruption of the anatomic fovea. Abnormal vitreous traction is involved in the formation of macular holes. Both glial cells and hyalocytes contribute to epiretinal membrane formation in IMH. In order to gain further insight into the pat...
Background: Stunting affects ∼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood.Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting.Design: We measured 677 seru...
Background
The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations have been linked to better physical performance; however, it is unknown whether klotho relates to frailty status in older adults.
Methods
Plasma klotho was measured in 774 participants aged ≥...
Identifying biological signatures of aging in order to gain insight into molecular pathways involved in healthy aging. To identify proteomic signatures of age, we measured 1306 proteins in plasma samples of 260 healthy men and women, aged 22–93 years, from the Baltimore Longitudinal study of Aging (BLSA) and the Genetic and Epigenetic Signatures of...
Klotho is a recently discovered hormone with demonstrated anti-aging properties in animal studies. In older humans, evidence has linked plasma klotho with longevity. Insulin signaling is associated with longevity in animals and in humans, mediated in part by the accumulation of fat mass common in aging. Whether klotho is part of this longevity path...
Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and post-translational modifications, have been...
