| 1. |
- Abbasi, Mojdeh, et al.
(författare)
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Molecular Mechanisms of Glaucoma Pathogenesis with Implications to Caveolin Adaptor Protein and Caveolin-Shp2 Axis
- 2023
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Ingår i: Aging and Disease. - : INT SOC AGING & DISEASE. - 2152-5250.
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Forskningsöversikt (refereegranskat)abstract
- Glaucoma is a common retinal disorder characterized by progressive optic nerve damage, resulting in visual impairment and potential blindness. Elevated intraocular pressure (IOP) is a major risk factor, but some patients still experience disease progression despite IOP-lowering treatments. Genome-wide association studies have linked variations in the Caveolin1/2 (CAV-1/2) gene loci to glaucoma risk. Cav-1, a key protein in caveolae membrane invaginations, is involved in signaling pathways and its absence impairs retinal function. Recent research suggests that Cav-1 is implicated in modulating the BDNF/TrkB signaling pathway in retinal ganglion cells, which plays a critical role in retinal ganglion cell (RGC) health and protection against apoptosis. Understanding the interplay between these proteins could shed light on glaucoma pathogenesis and provide potential therapeutic targets.
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| 2. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden
- 2024
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Ingår i: Aging and Disease. - Fort Wortht, TX, United States : Buck Institute for Age Research. - 2152-5250.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Orthostatic hypotension (OH) is more common in the elderly, and associated with increased mortality. However, its implications in 85-year-olds are not known.Methods: In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH.Results: Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality.Conclusion: OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.
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| 3. |
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| 4. |
- Carrera-Bastos, Pedro, et al.
(författare)
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Serum Zonulin and endotoxin levels in exceptional longevity versus precocious myocardial infarction
- 2018
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Ingår i: Aging and Disease. - 2152-5250. ; 9:2, s. 317-321
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Tidskriftsartikel (refereegranskat)abstract
- Endotoxemia-induced inflammation has been associated with insulin resistance and atherosclerosis, ultimately increasing the risk of coronary heart disease. Increased intestinal permeability is an important event leading to endotoxemia. This study aims to elucidate the possible association between endotoxin (lipopolysaccharide) and zonulin (a biomarker of intestinal permeability) levels and the risk of coronary heart disease, and thus healthy aging. Serum levels of zonulin, lipopolysaccharide and soluble CD14 (a protein that binds lipopolysaccharide) were measured in disease-free centenarians, young healthy controls and patients with precocious acute myocardial infarction. Disease-free centenarians had significantly lower levels of serum zonulin (P < 0.01) and lipopolysaccharide (P < 0.001) than young patients with acute myocardial infarction, and had significantly lower concentrations of serum lipopolysaccharide than young healthy controls (P < 0.05). No significant differences were found for soluble CD14 between groups. Our findings may stimulate further research into the role played by intestinal permeability and endotoxemia not only in coronary heart disease but also in lifespan modulation.
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| 5. |
- Garcia-Serrano, Alba, et al.
(författare)
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Cognitive Impairment and Metabolite Profile Alterations in the Hippocampus and Cortex of Male and Female Mice Exposed to a Fat and Sugar-Rich Diet are Normalized by Diet Reversal
- 2022
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Ingår i: Aging and Disease. - 2152-5250. ; 13:1, s. 267-283
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes impacts on brain metabolism, structure and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. However, it remains to be determined whether brain dysfunction induced by obesogenic diets results from permanent brain alterations. We tested the hypothesis that an obesogenic diet (high-fat and high-sucrose diet; HFHSD) causes reversible changes in hippocampus and cortex metabolism and alterations in behavior. Mice were exposed to HFHSD for 24 weeks or for 16 weeks followed by 8 weeks of diet normalization. Development of the metabolic syndrome, changes in behavior, and brain metabolite profiles by magnetic resonance spectroscopy (MRS) were assessed longitudinally. Control mice were fed an ingredient-matched low-fat and low-sugar diet. Mice fed the HFHSD developed obesity, glucose intolerance and insulin resistance, with a more severe phenotype in male than female mice. Relative to controls, both male and female HFHSD-fed mice showed increased anxiety-like behavior, impaired memory in object recognition tasks, but preserved working spatial memory as evaluated by spontaneous alternation in a Y-maze. Alterations in the metabolite profiles were observed both in the hippocampus and cortex but were more distinct in the hippocampus. HFHSD-induced metabolic changes included altered levels of lactate, glutamate, GABA, glutathione, taurine, N-acetylaspartate, total creatine and total choline. Notably, HFHSD-induced metabolic syndrome, anxiety, memory impairment, and brain metabolic alterations recovered upon diet normalization for 8 weeks. In conclusion, cortical and hippocampal derangements induced by long-term HFHSD consumption are reversible rather than being the result of permanent tissue damage.
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| 6. |
- Korner, Sonja, et al.
(författare)
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Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population
- 2019
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Ingår i: Aging and Disease. - Fort Worth : International Society on Aging & Disease. - 2152-5250. ; 10:2, s. 205-216
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly affecting upper and lower motor neurons in the brain and spinal cord. Pathogenesis of ALS is still unclear, and a multifactorial etiology is presumed. The remarkable clinical heterogeneity between different phenotypes of ALS patients suggests that environmental and lifestyle factors could play a role in onset and progression of ALS. We analyzed a cohort of 117 ALS patients and 93 controls. ALS patients and controls were compared regarding physical activity, dietary habits, smoking, residential environment, potentially toxic environmental factors and profession before symptom onset and throughout the disease course. Data were collected by a personal interview. For statistical analysis descriptive statistics, statistical tests and analysis of variance were used. ALS patients and controls did not differ regarding smoking, diet and extent of physical training. No higher frequency of toxic influences could be detected in the ALS group. ALS patients lived in rural environment considerably more often than the control persons, but this was not associated with a higher percentage of occupation in agriculture. There was also a higher percentage of university graduates in the ALS group. Patients with bulbar onset were considerably more often born in an urban environment as compared to spinal onset. Apart from education and environment, ALS phenotypes did not differ in any investigated environmental or life-style factor. The rate of disease progression was not influenced by any of the investigated environmental and life-style factors. The present study could not identify any dietary habit, smoking, physical activity, occupational factor as well as toxic influences as risk factor or protective factor for onset or progression of ALS. Living in rural environment and higher education might be associated with higher incidence of ALS.
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| 7. |
- Nilsson, Peter
(författare)
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Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA).
- 2014
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Ingår i: Aging and Disease. - 2152-5250. ; 5:2, s. 109-113
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Forskningsöversikt (refereegranskat)abstract
- An increase in peripheral vascular resistance at rest is not routinely observed in healthy older persons, but often associated with increased stiffness of central elastic arteries, as hallmarks of aging effects on the vasculature, referred to as early vascular aging (EVA). In clinical practice, the increased arterial stiffness translates into increased brachial and central systolic blood pressure and corresponding pulse pressure in subjects above 50 years of age, as well as increased carotid-femoral pulse wave velocity (c-f PWV), a marker of arterial stiffness. A c-f PWV value ≥ 10 m/s is currently defined as a threshold for increased cardiovascular risk, based on consensus statement from 2012. Prevention and treatment strategies include a healthy lifestyle and the control of risk factors via appropriate drug therapy to achieve vascular protection related to EVA. New drugs are under development for vascular protection, for example the selective Angiotensin II (AT2) receptor agonist called compound 21. One target group for early intervention could be members of risk families including subjects with early onset cardiovascular disease.
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| 8. |
- Yu, Haiyang, et al.
(författare)
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Association between Parkinson’s Disease and Diabetes Mellitus : From Epidemiology, Pathophysiology and Prevention to Treatment
- 2022
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Ingår i: Aging and Disease. - 2152-5250. ; 13:6, s. 1591-1605
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) and Parkinson’s disease (PD) are both age-related diseases of global concern being among the most common chronic metabolic and neurodegenerative diseases, respectively. While both diseases can be genetically inherited, environmental factors play a vital role in their pathogenesis. Moreover, DM and PD have common underlying molecular mechanisms, such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and microbial dysbiosis. Recently, epidemiological and experimental studies have reported that DM affects the incidence and progression of PD. Moreover, certain antidiabetic drugs have been proven to decrease the risk of PD and delay its progression. In this review, we elucidate the epidemiological and pathophysiological association between DM and PD and summarize the antidiabetic drugs used in animal models and clinical trials of PD, which may provide reference for the clinical translation of antidiabetic drugs in PD treatment.
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