Serum Uric Acid and Bone Health in Middle-Aged and Elderly Hypertensive Patients: A Potential U-Shaped Association and Implications for Future Fracture Risk

Metabolites, Journal Year: 2025, Volume and Issue: 15(1), P. 15 - 15

Published: Jan. 3, 2025

The influence of serum uric acid (SUA) on bone metabolism, as suggested by previous studies, remains a contentious issue. SUA plays complex role in health and hypertension, making it challenging to discern its impact the skeletal status middle-aged elderly hypertensive patients. This study aims elucidate effects health, with particular focus association osteoporosis risk fractures. Multiple linear regression analyzed levels against mineral density (BMD) future fracture risk. Additionally, multivariate logistic was used examine between osteoporosis. Dose-response relationship analysis conducted using generalized smooth curve fitting (GSCF) restricted cubic spline (RCS) methods. With exception total femur region, BMD showed positive connection. GSCF revealed an inverted U-shaped BMD, alongside trend FRAX scores. Moreover, RCS indicated levels, higher risks identified first third tertiles compared second tertile. In individuals older is substantially linked health. identification relationships scores highlights nuanced SUA. These findings suggest that both low high may adversely affect emphasizing need for further research.

Language: Английский

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Diet and lifestyle impact the development and progression of Alzheimer’s dementia

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: June 29, 2023

Dementia is a growing public health concern, with an estimated prevalence of 57 million adults worldwide. Alzheimer’s disease (AD) accounts for 60–80% the cases. Clinical trials testing potential drugs and neuroprotective agents have proven futile, currently approved only provide symptomatic benefits. Emerging epidemiological clinical studies suggest that lifestyle changes, including diet physical activity, offer alternative therapeutic route slowing preventing cognitive decline dementia. Age single most common risk factor dementia, it associated cellular bioenergetics metabolic processes. Therefore, nutrient-rich critical optimal brain health. Furthermore, type 2 diabetes (T2D) AD, diets reduce T2D may confer neuroprotection. Foods predominant in Mediterranean, MIND, DASH diets, fruits, leafy green vegetables, fish, nuts, olive oil, prevent or slow decline. The mechanisms by which these nutrients promote health, however, are not yet completely understood. Other dietary approaches eating regimes, ketogenic intermittent fasting, also emerging as beneficial This review summarizes pathophysiology, factors, pathways activated several regimes shown promising results promoting

Language: Английский

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Integrative metabolomics science in Alzheimer’s disease: Relevance and future perspectives

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101987 - 101987

Published: June 19, 2023

Language: Английский

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The fructose survival hypothesis for obesity

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2023, Volume and Issue: 378(1885)

Published: July 24, 2023

The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) aims to protect animals in advance crisis. is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation increased blood pressure. process initiated the ingestion or stimulating endogenous production via polyol pathway. Unlike other nutrients, reduces active energy (adenosine triphosphate) cell, while blocking its regeneration stores. This mediated intracellular uric acid, mitochondrial oxidative stress, inhibition AMP kinase stimulation vasopressin. Mitochondrial phosphorylation suppressed, glycolysis stimulated. While this aimed be modest short-lived, humans exaggerated due gain ‘thrifty genes’ coupled with a western diet rich foods contain generate fructose. We propose excessive metabolism not only explains but epidemics diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular Alzheimer's dementia, even ageing. Moreover, unites current hypotheses on obesity. Reducing activation and/or pathway benefit health-span. article part discussion meeting issue ‘Causes obesity: theories, conjectures evidence (Part I)’.

Language: Английский

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APOE Genotype Influences on The Brain Metabolome of Aging Mice - Role for Mitochondrial Energetics in Mechanisms of Resilience in APOE2 Genotype.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Alzheimer's disease (AD) risk and progression are significantly influenced by APOE genotype with APOE4 increasing APOE2 decreasing susceptibility compared to APOE3. While the effect of those genotypes was extensively studied on blood metabolome, less is known about their impact in brain. Here we investigated impacts aging brain metabolic profiles across lifespan, using human APOE-targeted replacement mice. Biocrates P180 targeted metabolomics platform used measure a broad range metabolites probing various processes. In all report changes acylcarnitines, biogenic amines, amino acids, phospholipids sphingomyelins during aging. The decreased ratio medium long-chain acylcarnitine suggests reduced level fatty acid β-oxidation thus possibility mitochondrial dysfunction as these animals age. Additionally, APOE2/2 mice had altered branch-chain acids (BCAA) profile increased downstream metabolite C5 acylcarnitine, indicating branched-chain utilization TCA cycle better energetic endowed this protective genotype. We results dorsolateral prefrontal cortex metabolomic data from Religious Orders Study/Memory Aging Project, found that carriers APOE2/3 lower markers impaired BCAA katabolism, including tiglyl carnitine, methylmalonate 3-methylglutaconate. summary, suggest potential involvement nominate humanized mouse models for further study AD, aging, energy. have previously shown plasma be associated incident dementia, higher levels AD pathology cognitive impairment. Those findings together our current could potentially explain AD-protective enabling energy decline β-oxidation.

Language: Английский

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Do microglia metabolize fructose in Alzheimer’s disease?

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 15, 2025

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder with a complex etiology. While emerging AD therapeutics can slow cognitive decline, they may worsen dementia in certain groups of individuals. Therefore, alternative treatments are much needed. Microglia, the brain resident macrophages, have potential to be novel therapeutic targets as regulate many facets AD, including lipid droplet (LD) accumulation, amyloid beta (Aβ) clearance, and neuroinflammation. To carry out such functions, microglia undergo phenotypic changes, which linked shifts metabolism substrate utilization. homeostatic driven by oxidative phosphorylation (OXPHOS) glycolysis, aging shift further towards glycolysis. Interestingly, this "metabolic reprogramming" increase fructose metabolism. In brain, predominantly express transporter SLC2A5 (GLUT5), enzymes involved fructolysis endogenous production, their expression being upregulated disease. Here, we review evidence for uptake, breakdown, production microglia. We also evaluate literature targeting periphery assess its ability modulate microglial function AD. The transport utilize fructose, coupled well-established role metabolic dysfunction, supports notion that target

Language: Английский

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Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 483 - 483

Published: April 17, 2025

Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as world population grows ages. Oxidative stress inflammation crucially implicated in triggering progression multiple sclerosis, Alzheimer’s disease, amyotrophic lateral Huntington’s Parkinson’s even stroke. In this narrative review, we examine role xanthine oxidoreductase (XOR) activities products all above-cited diseases. The redox imbalance responsible for oxidative could arise from excess reactive oxygen nitrogen species resulting XOR, well deficiency its main product, uric acid (UA), which is pivotal antioxidant system blood. fact, with exception stroke, serum UA levels inversely related onset these disorders. inverse correlation observed between level uricemia presence diseases suggests a neuroprotective UA. also caused by ischemia reperfusion, condition XOR action has been recognized contributing factor tissue damage. findings reported review be useful addressing clinical decision-making treatment optimization.

Language: Английский

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Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer’s disease: A narrative review

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 102, P. 102578 - 102578

Published: Nov. 13, 2024

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on healthcare system, society, and economy due to increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques tau protein neurofibrillary tangles, which are two main hallmarks this devastating neurodegenerative disease, have not provided results in terms their neuropathological outcomes nor met expected clinical end-points. Ageing, genetic environmental risk factors, along different symptoms suggest that AD complex heterogeneous disorder multiple interconnected pathological pathways rather than single entity. In present review, we highlight discuss various non-canonical, Aβ-independent mechanisms, like gliosis, unhealthy dietary intake, lipid sugar signaling, cerebrovascular damage contribute onset development AD. We emphasize challenging traditional "amyloid cascade hypothesis" may improve our understanding age-related syndrome help fight progressive cognitive decline

Language: Английский

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The fructose survival hypothesis as a mechanism for unifying the various obesity hypotheses

Obesity, Journal Year: 2023, Volume and Issue: 32(1), P. 12 - 22

Published: Oct. 17, 2023

Abstract The pathogenesis of obesity remains contested. Although genetics is important, the rapid rise in with Western culture and diet suggests an environmental component. Today, some major hypotheses for include energy balance hypothesis, carbohydrate‐insulin model, protein‐leverage seed oil hypothesis. Each hypothesis has its own support, creating controversy over their respective roles driving obesity. Here we propose that all are largely correct can be unified by another dietary fructose survival Fructose unique resetting ATP levels to a lower level cell as consequence suppressing mitochondrial function, while blocking replacement from fat. low intracellular result carbohydrate‐dependent hunger, impaired satiety (leptin resistance), metabolic effects increased intake energy‐dense fats. This emphasizes role carbohydrates stimulating fat provides main source energy. Thus, disorder metabolism, which there usable (ATP) setting elevated total leads independent excess drives weight gain.

Language: Английский

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Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta‐analysis based on latest evidence

Brain and Behavior, Journal Year: 2023, Volume and Issue: 13(10)

Published: Sept. 4, 2023

Abstract Objective Previous studies have found the potential role of gout or hyperuricemia in subsequent development Alzheimer's disease (AD) but reported inconsistent results. We conducted current meta‐analysis to evaluate whether an association exists between gout/ and AD. Methods systematically searched PubMed EMBASE for published cohort that measured risk AD subject with up May 20, 2023. Data extraction was employed by two authors independently. Rev Man 5.3 Stata 15.0 software were used calculate relative ratio (RR) hazard (HR) including studies. Subgroup analysis performed assess sources heterogeneity. A random‐effects model adopted when heterogeneity present. The funnel plot, Begg's test, Egger's test publication bias. Results After rigorous screening, seven eligible included final analyses. Pooled results indicated decreases (RR: 0.69, 95% CI: 0.64∼0.72), a high 93%. analyses showed regional distribution source tests as well visual inspection plot suggested no bias Conclusion findings might protective effect against This negative correlation should be verified more due existence substantial

Language: Английский

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