| 1. |
- Ehinger, Johannes K., et al.
(författare)
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Mitochondrial function in peripheral blood cells across the human lifespan
- 2024
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Ingår i: npj Aging. - 2731-6068. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is considered a hallmark of aging. Up to now, a gradual decline of mitochondrial respiration with advancing age has mainly been demonstrated in human muscle tissue. A handful of studies have examined age-related mitochondrial dysfunction in human blood cells, and only with small sample sizes and mainly in platelets. In this study, we analyzed mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and platelets from 308 individuals across the human lifespan (0–86 years). In regression analyses, with adjustment for false discovery rate (FDR), we found age-related changes in respiratory measurements to be either small or absent. The main significant changes were an age-related relative decline in complex I-linked respiration and a corresponding rise of complex II-linked respiration in PBMCs. These results add to the understanding of mitochondrial dysfunction in aging and to its possible role in immune cell and platelet senescence.
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| 2. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. (C) 2016 The Author(s). Published by Elsevier Inc.
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| 3. |
- Spaulding, Kirsty, et al.
(författare)
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Dynamics of Hippocampal Neurogenesis in Adult Humans
- 2013
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Ingår i: Cell. - Maryland Heights, MO, USA : Elsevier. - 0092-8674 .- 1097-4172. ; 153:6, s. 1219-1227
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Tidskriftsartikel (refereegranskat)abstract
- Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have func- tional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear- bomb-test-derived 14C in genomic DNA, and we present an integrated model of the cell turnover dy- namics. We found that a large subpopulation of hip- pocampal neurons constituting one-third of the neu- rons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neu- rons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neuro- genesis may contribute to human brain function.
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| 4. |
- Westerlund, Emil, et al.
(författare)
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Correlation of mitochondrial respiration in platelets, peripheral blood mononuclear cells and muscle fibers
- 2024
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Ingår i: Heliyon. - 2405-8440. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest for the possibility of using peripheral blood cells (including platelets) as markers for mitochondrial function in less accessible tissues. Only a few studies have examined the correlation between respiration in blood and muscle tissue, with small sample sizes and conflicting results. This study investigated the correlation of mitochondrial respiration within and across tissues. Additional analyses were performed to elucidate which blood cell type would be most useful for assessing systemic mitochondrial function. There was a significant but weak within tissue correlation between platelets and peripheral blood mononuclear cells (PBMCs). Neither PBMCs nor platelet respiration correlated significantly with muscle respiration. Muscle fibers from a group of athletes had higher mass-specific respiration, due to higher mitochondrial content than non-athlete controls, but this finding was not replicated in either of the blood cell types. In a group of patients with primary mitochondrial diseases, there were significant differences in blood cell respiration compared to healthy controls, particularly in platelets. Platelet respiration generally correlated better with the citrate synthase activity of each sample, in comparison to PBMCs. In conclusion, this study does not support the theory that blood cells can be used as accurate biomarkers to detect minor alterations in muscle respiration. However, in some instances, pronounced mitochondrial abnormalities might be reflected across tissues and detectable in blood cells, with more promising findings for platelets than PBMCs.
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| 5. |
- Westerlund, Emil, et al.
(författare)
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Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease
- 2017
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 83, s. 455-465
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Tidskriftsartikel (refereegranskat)abstract
- Diagnosing mitochondrial disease (MD) is a challenge. In addition to genetic analyses, clinical practice is to perform invasive procedures such as muscle biopsy for biochemical and histochemical analyses. Blood cell respirometry is rapid and noninvasive. Our aim was to explore its possible role in diagnosing MD.MethodsBlood samples were collected from 113 pediatric patients, for whom MD was a differential diagnosis. A respiratory analysis model based on ratios (independent of mitochondrial specific content) was derived from a group of healthy controls and tested on the patients. The diagnostic accuracy of platelet respirometry was evaluated against routine diagnostic investigation.ResultsMD prevalence in the cohort was 16%. A ratio based on the respiratory response to adenosine diphosphate in the presence of complex I substrates had 96% specificity for disease and a positive likelihood ratio of 5.3. None of the individual ratios had sensitivity above 50%, but a combined model had 72% sensitivity.ConclusionNormal findings of platelet respirometry are not able to rule out MD, but pathological results make the diagnosis more likely and could strengthen the clinical decision to perform further invasive analyses. Our results encourage further study into the role of blood respirometry as an adjunct diagnostic tool for MD.
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| 6. |
- Westerlund, Emil, et al.
(författare)
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Pre-ART retention in care and prevalence of tuberculosis among HIV-infected children at a district hospital in southern Ethiopia
- 2014
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Ethiopian epidemic is currently on the wane. However, the situation for infected children is in some ways lagging behind due to low treatment coverage and deficient prevention of mother-to-child transmission. Too few studies have examined HIV infected children presenting to care in low-income countries in general. Considering the presence of local variations in the nature of the epidemic a study in Ethiopia could be of special value for the continuing fight against HIV. The aim of this study is to describe the main characteristics of children with HIV presenting to care at a district hospital in a resource-limited area in southern Ethiopia. The aim was also to analyse factors affecting pre-ART loss to follow-up, time to ART-initiation and disease stage upon presentation. Methods: This was a prospective cohort study. The data analysed were collected in 2009 for the period January 2003 through December 2008 at Arba Minch Hospital and additional data on the ART-need in the region were obtained from official reports. Results: The pre-ART loss to follow-up rate was 29.7%. Older children (10-14 years) presented in a later stage of their disease than younger children (76.9% vs. 45.0% in 0-4 year olds, chi-square test, chi(2) = 8.8, P = 0.01). Older girls presented later than boys (100.0% vs. 57.1%, Fisher's exact test, P = 0.02). Children aged 0-4 years were more likely to be lost to follow-up (40.0 vs. 21.8%, chi-square test, chi(2) = 5.4, P = 0.02) and had a longer time to initiate ART (Cox regression analysis, HR: 0.50, 95% CI: 0.25-0.97, P = 0.04, controlling for sex, place of residence, enrolment phase and WHO clinical stage upon presentation). Neither sex was overrepresented in the sample. Tuberculosis prevalence upon presentation and previous history of tubercolosis were 14.5% and 8% respectively. Conclusions: The loss to follow-up is alarmingly high and children present too late. Further research is needed to explore specific causes and possible solutions.
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